Emerging Material-Based Approaches to Chronic and Infectious Diseases

Journal Name	Impact Factor	CiteScore	Launched Year	First Decision (median)	APC
Antibiotics antibiotics	4.3	7.3	2012	15.8 Days	CHF 2900
Pharmaceutics pharmaceutics	4.9	7.9	2009	15.5 Days	CHF 2900
Pharmaceuticals pharmaceuticals	4.3	6.1	2004	13.9 Days	CHF 2900
Methods and Protocols mps	2.3	3.6	2018	30.6 Days	CHF 1800

19 pages, 3206 KiB

Open AccessArticle

Development of a Citric-Acid-Modified Cellulose Adsorbent Derived from Moringa peregrina Leaf for Adsorptive Removal of Citalopram HBr in Aqueous Solutions

by Syed Najmul Hejaz Azmi, Wafa Mustafa Al Lawati, Umaima Hamed Abdullah Al Hoqani, Ekhlas Al Aufi, Khalsa Al Hatmi, Jumana Salim Al Zadjali, Nafisur Rahman, Mohd Nasir, Habibur Rahman and Shah A. Khan

Pharmaceuticals 2022, 15(6), 760; https://doi.org/10.3390/ph15060760 - 17 Jun 2022

Cited by 17 | Viewed by 3065

Abstract

A citric-acid-modified Moringa peregrina leaf substrate was prepared and studied as an effective adsorbent for the adsorptive removal of citalopram HBr (CTM). FTIR spectra were utilized to characterize the prepared solid. The effects of experimental variables on the percentage removal of citalopram HBr [...] Read more.

A citric-acid-modified Moringa peregrina leaf substrate was prepared and studied as an effective adsorbent for the adsorptive removal of citalopram HBr (CTM). FTIR spectra were utilized to characterize the prepared solid. The effects of experimental variables on the percentage removal of citalopram HBr were investigated using response surface methodology. The optimum conditions selected for removal of CTM were 7 and 4 min, 0.17 g per 50 mL and 35 mg·L⁻¹ for pH, contact time, adsorbent dose and initial concentration of CTM, respectively. Under the optimized experimental conditions, 82.59% CTM (35 mg·L⁻¹) was removed. The Langmuir isotherm, Freundlich isotherm, pseudo second-order kinetic model and diffusion-chemisorption model explained the adsorption data successfully. The maximum adsorption capacity at 298 K was 8.58 mg·g⁻¹. A thermodynamic study illustrated that CTM adsorption was spontaneous and endothermic in nature. Full article

(This article belongs to the Topic Emerging Material-Based Approaches to Chronic and Infectious Diseases)

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14 pages, 1893 KiB

Open AccessArticle

Mepirapim, a Novel Synthetic Cannabinoid, Induces Addiction-Related Behaviors through Neurochemical Maladaptation in the Brain of Rodents

by Kwang-Hyun Hur, YouYoung Lee, Audrey Lynn Donio, Shi-Xun Ma, Bo-Ram Lee, Seon-Kyung Kim, Jae-Gyeong Lee, Young-Jung Kim, MinJeong Kim, SeolMin Yoon, SooYeun Lee, Yong-Sup Lee, Seok-Yong Lee and Choon-Gon Jang

Pharmaceuticals 2022, 15(6), 710; https://doi.org/10.3390/ph15060710 - 3 Jun 2022

Cited by 3 | Viewed by 3665

Abstract

Mepirapim is a synthetic cannabinoid that has recently been abused for recreational purposes. Although serious side effects have been reported from users, the dangerous pharmacological effects of Mepirapim have not been scientifically demonstrated. In this study, we investigated the addictive potential of Mepirapim [...] Read more.

Mepirapim is a synthetic cannabinoid that has recently been abused for recreational purposes. Although serious side effects have been reported from users, the dangerous pharmacological effects of Mepirapim have not been scientifically demonstrated. In this study, we investigated the addictive potential of Mepirapim through an intravenous self-administration test and a conditioned place preference test in rodents. Moreover, to determine whether the pharmacological effects of Mepirapim are mediated by cannabinoid receptors, we investigated whether Mepirapim treatment induces cannabinoid tetrad symptoms in mice. Lastly, to identify Mepirapim induced neurochemical maladaptation in the brains of mice, we performed microdialysis, western blots and neurotransmitter enzyme-linked immunosorbent assays. In the results, Mepirapim supported the maintenance of intravenous self-administration and the development of conditioned place preference. As a molecular mechanism of Mepirapim addiction, we identified a decrease in GABAeric signalling and an increase in dopaminergic signalling in the brain reward circuit. Finally, by confirming the Mepirapim-induced expression of cannabinoid tetrad symptoms, we confirmed that Mepirapim acts pharmacologically through cannabinoid receptor one. Taken together, we found that Mepirapim induces addiction-related behaviours through neurochemical maladaptation in the brain. On the basis of these findings, we propose the strict regulation of recreational abuse of Mepirapim. Full article

(This article belongs to the Topic Emerging Material-Based Approaches to Chronic and Infectious Diseases)

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11 pages, 1299 KiB

Open AccessArticle

Multi Evaluation of a Modified GoldNano Carb Test for Carbapenemase Detection in Clinical Isolates of Gram-Negative Bacilli

by Arpasiri Srisrattakarn, Aroonlug Lulitanond, Nicha Charoensri, Lumyai Wonglakorn, Suthida Kenprom, Chutipapa Sukkasem, Waewta Kuwatjanakul, Sirikan Piyapatthanakul, Onphailin Luanphairin, Wichuda Phukaw, Kunthida Khanchai, Jantira Pasuram, Chotechana Wilailuckana, Jureerut Daduang and Aroonwadee Chanawong

Antibiotics 2022, 11(5), 684; https://doi.org/10.3390/antibiotics11050684 - 18 May 2022

Cited by 3 | Viewed by 2473

Abstract

Carbapenemase-producing Gram-negative bacteria have been increasingly reported. Simple and sensitive methods for carbapenemase detection are still needed. In this study, a gold nanoparticle (AuNP) solution was modified by the addition of zinc sulfate (ZnSO₄) for improving the conventional GoldNano Carb (cGoldC) [...] Read more.

Carbapenemase-producing Gram-negative bacteria have been increasingly reported. Simple and sensitive methods for carbapenemase detection are still needed. In this study, a gold nanoparticle (AuNP) solution was modified by the addition of zinc sulfate (ZnSO₄) for improving the conventional GoldNano Carb (cGoldC) test, and the modified GoldC (mGoldC) test was then evaluated for phenotypic detection of carbapenemase production in Gram-negative bacilli clinical isolates. ZnSO₄ was added to give final concentrations of 0.25, 0.5, 0.75, and 1 mM. The performance of the mGoldC test was evaluated in Enterobacterales, Acinetobacter spp., and Pseudomonas aeruginosa isolates from six hospitals in different regions using polymerase chain reaction (PCR) as a gold standard. The AuNP solution with 0.25 mM ZnSO₄ was used for the mGoldC test. Evaluation of the mGoldC test in 495 Enterobacterales, 212 Acinetobacter spp., and 125 P. aeruginosa isolates (including 444 carbapenemase producers and 388 non-carbapenemase producers) revealed sensitivity, specificity, a positive likelihood ratio, and a negative likelihood ratio of 98.6%, 98.2%, 54.7, and 0.01, respectively. This test is fast, easy to perform, cost-effective (~0.25 USD per test), and highly sensitive and specific for routine carbapenemase detection, thus leading to effective antimicrobial therapy and infection control measures. Full article

(This article belongs to the Topic Emerging Material-Based Approaches to Chronic and Infectious Diseases)

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11 pages, 736 KiB

Open AccessArticle

Treatment Outcome in Patients with Mycobacterium abscessus Complex Lung Disease: The Impact of Tigecycline and Amikacin

by Jeng-How Yang, Ping-Huai Wang, Sheng-Wei Pan, Yu-Feng Wei, Chung-Yu Chen, Ho-Sheng Lee, Chin-Chung Shu and Ting-Shu Wu

Antibiotics 2022, 11(5), 571; https://doi.org/10.3390/antibiotics11050571 - 25 Apr 2022

Cited by 9 | Viewed by 3436

Abstract

Background: The contemporary guidelines have recommended multiple antimicrobial therapies along with oral macrolides for the treatment of Mycobacterium abscessus complex lung disease (MABC-LD). However, there is little evidence supporting the parenteral tigecycline-containing regimens against MABC-LD. Therefore, we conducted this study to evaluate the [...] Read more.

Background: The contemporary guidelines have recommended multiple antimicrobial therapies along with oral macrolides for the treatment of Mycobacterium abscessus complex lung disease (MABC-LD). However, there is little evidence supporting the parenteral tigecycline-containing regimens against MABC-LD. Therefore, we conducted this study to evaluate the effect of intravenous tigecycline-containing regimens on the treatment of MABC-LD. Methods: A retrospective study was conducted in 6 medical centers. Patients with MABC-LD that were followed up at ≥12 months were enrolled. Mycobacterium abscessus subspecies were identified by hsp65, rpoB, secA1 gene PCR, and sequencing. Antimicrobial susceptibility was determined for 34 patients using broth microdilution methods following the Clinical and Laboratory Standards Institute (CLSI) guideline. The microbiology and treatment outcomes were defined as either success or failure. The impacts of tigecycline and amikacin were adjusted for age, comorbidities, surgical resection, and radiologic scores. Results: During the study period, seventy-one patients were enrolled for final analysis. The microbiology failure rate was 61% (43/71) and the treatment failure rate was 62% (44/71). For M. abscessus complex, 97% (33/34) of tigecycline MIC were ≤1 mg/L. Amikacin also demonstrated great susceptibility (94.1%; 32/34). Treatment with regimens containing tigecycline plus amikacin provided better microbiology success (adjusted OR 17.724; 95% CI 1.227–267.206) and treatment success (adjusted OR 14.085; 95% CI 1.103–166.667). Conclusion: The outcome of MABC-LD is always unsatisfactory. Treatment regimens with oral macrolide in combination with tigecycline and amikacin were correlated with increased microbiology success and less treatment failure. Full article

(This article belongs to the Topic Emerging Material-Based Approaches to Chronic and Infectious Diseases)

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14 pages, 2631 KiB

Open AccessArticle

Melittin from Bee Venom Encapsulating Electrospun Fibers as a Potential Antimicrobial Wound Dressing Patches for Skin Infections

by Walaa S. Aburayan, Areej M. Alajmi, Ahmed J. Alfahad, Wijdan K. Alsharif, Abdullah A. Alshehri, Rayan Y. Booq, Samar A. Alsudir, Fatemah M. Alsulaihem, Haitham A. Bukhary, Moutaz Y. Badr, Essam J. Alyamani and Essam A. Tawfik

Pharmaceutics 2022, 14(4), 725; https://doi.org/10.3390/pharmaceutics14040725 - 28 Mar 2022

Cited by 18 | Viewed by 3653

Abstract

Skin infection compromises the body’s natural defenses. Several antibiotics are no longer effective owing to the evolution of antimicrobial-resistant (AMR) bacteria, hence, the constant development of novel antibacterial agents. Naturally occurring antibacterial agents may be potential candidates for AMR bacterial infection treatments; however, [...] Read more.

Skin infection compromises the body’s natural defenses. Several antibiotics are no longer effective owing to the evolution of antimicrobial-resistant (AMR) bacteria, hence, the constant development of novel antibacterial agents. Naturally occurring antibacterial agents may be potential candidates for AMR bacterial infection treatments; however, caution should be taken when administering such agents due to the high incidence of toxicity. A fibrous material system from a biocompatible polymer that could be used as a skin patch for skin infections treatment caused by AMR bacteria is proposed in this study. Bee venom’s active ingredient, melittin, was fabricated using electrospinning technology. Scanning electron microscopy showed that melittin-loaded fibers had smooth surfaces with no signs of beads or pores. The average diameter of this fibrous system was measured to be 1030 ± 160 nm, indicating its successful preparation. The melittin fibers’ drug loading and entrapment efficiency (EE%) were 49 ± 3 µg/mg and 84 ± 5%, respectively. This high EE% can be another successful preparatory criterion. An in vitro release study demonstrated that 40% of melittin was released after 5 min and achieved complete release after 120 min owing to the hydrophilic nature of the PVP polymer. A concentration of ≤10 µg/mL was shown to be safe for use on human dermal fibroblasts HFF-1 after 24-h exposure, while an antibacterial MIC study found that 5 μg/mL was the effective antimicrobial concentration for S. aureus, A. baumannii, E. coli and Candida albicans yeast. A melittin-loaded fibrous system demonstrated an antibacterial zone of inhibition equivalent to the control (melittin discs), suggesting its potential use as a wound dressing patch for skin infections. Full article

(This article belongs to the Topic Emerging Material-Based Approaches to Chronic and Infectious Diseases)

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17 pages, 951 KiB

Open AccessReview

Antiosteoporosis Effects, Pharmacokinetics, and Drug Delivery Systems of Icaritin: Advances and Prospects

by Lifang Gao and Shuang-Qing Zhang

Pharmaceuticals 2022, 15(4), 397; https://doi.org/10.3390/ph15040397 - 24 Mar 2022

Cited by 36 | Viewed by 4569

Abstract

Osteoporosis is a systemic skeletal disorder affecting over 200 million people worldwide and contributes dramatically to global healthcare costs. Available anti-osteoporotic drug treatments including hormone replacement therapy, anabolic agents, and bisphosphonates often cause adverse events which limit their long-term use. Therefore, the application [...] Read more.

Osteoporosis is a systemic skeletal disorder affecting over 200 million people worldwide and contributes dramatically to global healthcare costs. Available anti-osteoporotic drug treatments including hormone replacement therapy, anabolic agents, and bisphosphonates often cause adverse events which limit their long-term use. Therefore, the application of natural products has been proposed as an alternative therapy strategy. Icaritin (ICT) is not only an enzyme-hydrolyzed product of icariin but also an intestinal metabolite of eight major flavonoids of the traditional Chinese medicinal plant Epimedium with extensive pharmacological activities, such as strengthening the kidney and reinforcing the bone. ICT displays several therapeutic effects, including osteoporosis prevention, neuroprotection, antitumor, cardiovascular protection, anti-inflammation, and immune-protective effect. ICT inhibits bone resorption activity of osteoclasts and stimulates osteogenic differentiation and maturation of bone marrow stromal progenitor cells and osteoblasts. As for the mechanisms of effect, ICT regulates relative activities of two transcription factors Runx2 and PPARγ, determines the differentiation of MSCs into osteoblasts, increases mRNA expression of OPG, and inhibits mRNA expression of RANKL. Poor water solubility, high lipophilicity, and unfavorable pharmacokinetic properties of ICT restrict its anti-osteoporotic effects, and novel drug delivery systems are explored to overcome intrinsic limitations of ICT. The paper focuses on osteogenic effects and mechanisms, pharmacokinetics and delivery systems of ICT, and highlights bone-targeting strategies to concentrate ICT on the ideal specific site of bone. ICT is a promising potential novel therapeutic agent for osteoporosis. Full article

(This article belongs to the Topic Emerging Material-Based Approaches to Chronic and Infectious Diseases)

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15 pages, 2290 KiB

Open AccessArticle

Design, Characterization, and In Vitro Assays on Muscle Cells of Endocannabinoid-like Molecule Loaded Lipid Nanoparticles for a Therapeutic Anti-Inflammatory Approach to Sarcopenia

by Eleonora Maretti, Susanna Molinari, Renata Battini, Cecilia Rustichelli, Eleonora Truzzi, Valentina Iannuccelli and Eliana Leo

Pharmaceutics 2022, 14(3), 648; https://doi.org/10.3390/pharmaceutics14030648 - 16 Mar 2022

Cited by 7 | Viewed by 2659

Abstract

Inflammatory processes play a key role in the pathogenesis of sarcopenia owing to their effects on the balance between muscle protein breakdown and synthesis. Palmitoylethanolamide (PEA), an endocannabinoid-like molecule, has been well documented for its anti-inflammatory properties, suggesting its possible beneficial use to [...] Read more.

Inflammatory processes play a key role in the pathogenesis of sarcopenia owing to their effects on the balance between muscle protein breakdown and synthesis. Palmitoylethanolamide (PEA), an endocannabinoid-like molecule, has been well documented for its anti-inflammatory properties, suggesting its possible beneficial use to counteract sarcopenia. The promising therapeutic effects of PEA are, however, impaired by its poor bioavailability. In order to overcome this limitation, the present study focused on the encapsulation of PEA in solid lipid nanoparticles (PEA-SLNs) in a perspective of a systemic administration. PEA-SLNs were characterized for their physico-chemical properties as well as cytotoxicity and cell internalization capacity on C2C12 myoblast cells. Their size was approximately 250 nm and the encapsulation efficiency reached 90%. Differential scanning calorimetry analyses demonstrated the amorphous state of PEA in the inner SLN matrix, which improved PEA dissolution, as observed in the in vitro assays. Despite the high internalization capacity observed with the flow cytometer (values between 85 and 94% after 14 h of incubation), the Nile Red labeled PEA-SLNs showed practically no toxicity towards myoblasts. Confocal analysis showed the presence of SLNs in the cytoplasm and not in the nucleus. These results suggest the potentiality provided by PEA-SLNs to obtain an innovative and side-effect-free tool in the medical treatment of sarcopenia. Full article

(This article belongs to the Topic Emerging Material-Based Approaches to Chronic and Infectious Diseases)

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21 pages, 66428 KiB

Open AccessArticle

Mechanic-Driven Biodegradable Polyglycolic Acid/Silk Fibroin Nanofibrous Scaffolds Containing Deferoxamine Accelerate Diabetic Wound Healing

by Shenfang Zha, Yohanes Kristo Sugiarto Utomo, Li Yang, Guizhao Liang and Wanqian Liu

Pharmaceutics 2022, 14(3), 601; https://doi.org/10.3390/pharmaceutics14030601 - 10 Mar 2022

Cited by 22 | Viewed by 3676

Abstract

The extracellular matrix (ECM), comprising of hundreds of proteins, mainly collagen, provides physical, mechanical support for various cells and guides cell behavior as an interactive scaffold. However, deposition of ECM, especially collagen content, is seriously impaired in diabetic wounds, which cause inferior mechanical [...] Read more.

The extracellular matrix (ECM), comprising of hundreds of proteins, mainly collagen, provides physical, mechanical support for various cells and guides cell behavior as an interactive scaffold. However, deposition of ECM, especially collagen content, is seriously impaired in diabetic wounds, which cause inferior mechanical properties of the wound and further delay chronic wound healing. Thus, it is critical to develop ECM/collagen alternatives to remodel the mechanical properties of diabetic wounds and thus accelerate diabetic wound healing. Here, we firstly prepared mechanic-driven biodegradable PGA/SF nanofibrous scaffolds containing DFO for diabetic wound healing. In our study, the results in vitro showed that the PGA/SF-DFO scaffolds had porous three-dimensional nanofibrous structures, excellent mechanical properties, biodegradability, and biocompatibility, which would provide beneficial microenvironments for cell adhesion, growth, and migration as an ECM/collagen alternative. Furthermore, the data in vivo showed PGA/SF-DFO scaffolds can adhere well to the wound and have excellent biodegradability, which is helpful to avoid secondary damage by omitting the removal process of scaffolds. The finite element analysis results showed that the application of silk fibroin-based scaffolds could significantly reduce the maximum stress around the wound. Besides, PGA/SF-DFO scaffolds induced collagen deposition, re-vascularization, recovered impaired mechanical properties up to about 70%, and ultimately accelerated diabetic wound healing within 14 days. Thus, our work provides a promising therapeutic strategy for clinically chronic wound healing. Full article

(This article belongs to the Topic Emerging Material-Based Approaches to Chronic and Infectious Diseases)

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15 pages, 8949 KiB

Open AccessArticle

Discrepancies in Antimicrobial Susceptibility between the JP2 and the Non-JP2 Genotype of Aggregatibacter actinomycetemcomitans

by Margareta Granlund, Carola Höglund Åberg, Anders Johansson and Rolf Claesson

Antibiotics 2022, 11(3), 317; https://doi.org/10.3390/antibiotics11030317 - 27 Feb 2022

Cited by 2 | Viewed by 2667

Abstract

The Aggregatibacter actinomycetemcomitans JP2 genotype is associated with high leukotoxin production and severe (aggressive) periodontitis. The aim of this study was to compare the antimicrobial susceptibility of JP2 and non-JP2 genotype strains. Minimal inhibitory concentrations (MICs) of 11 antimicrobials were determined for 160 [...] Read more.

The Aggregatibacter actinomycetemcomitans JP2 genotype is associated with high leukotoxin production and severe (aggressive) periodontitis. The aim of this study was to compare the antimicrobial susceptibility of JP2 and non-JP2 genotype strains. Minimal inhibitory concentrations (MICs) of 11 antimicrobials were determined for 160 A. actinomycetemcomitans of serotype a, b, or c, mostly isolated in Sweden or Ghana. MIC distributions for benzylpenicillin and fusidic acid revealed a more susceptible subpopulation for 38 serotype b strains, including the 32 of the JP2 genotype, with a benzylpenicillin MIC range of 0.125–0.5 mg/L. In contrast, benzylpenicillin MIC ≤ 16 mg/L was the estimated 99.5% epidemiological cutoff (ECOFF) of all strains. Beta-lactamase production was not detected. The fusidic acid MIC distribution of 11 strains of Aggregatibacter aphrophilus agreed with that found in non-JP2 strains. Cefotaxime, meropenem, levofloxacin, and trimethoprim–sulfamethoxazole MICs were all ≤0.25 mg/L, while MIC₉₀ values for amoxicillin, azithromycin and tetracycline were 1 mg/L. Metronidazole MICs varied between 0.5 and >256 mg/L. The discrepant findings indicate that A. actinomycetemcomitans may be divided into two separate wild types, with a suggested intrinsic reduced susceptibility for benzylpenicillin in the majority of non-JP2 genotype strains. Possible implications for the treatment of A. actinomycetemcomitans infections are discussed. Full article

(This article belongs to the Topic Emerging Material-Based Approaches to Chronic and Infectious Diseases)

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20 pages, 1698 KiB

Open AccessArticle

Effect of Farm Management Practices on Morbidity and Antibiotic Usage on Calf Rearing Farms

by Atte Sandelin, Outi Hälli, Heidi Härtel, Tuomas Herva, Liisa Kaartinen, Erja Tuunainen, Helena Rautala, Timo Soveri and Heli Simojoki

Antibiotics 2022, 11(2), 270; https://doi.org/10.3390/antibiotics11020270 - 18 Feb 2022

Cited by 7 | Viewed by 2925

Abstract

Antimicrobial resistance has been recognized as one of the top health threats to human society. Abundant use of antibiotics in both humans and animals has led to ever-increasing antibiotic resistance in bacteria. In food production, decreasing morbidity in beef herds would be an [...] Read more.

Antimicrobial resistance has been recognized as one of the top health threats to human society. Abundant use of antibiotics in both humans and animals has led to ever-increasing antibiotic resistance in bacteria. In food production, decreasing morbidity in beef herds would be an effective way to reduce the use of antibiotics. The objective of this retrospective observational study was to determine overall morbidity on calf rearing farms and to identify associated risk factors. Data were collected by questionnaire, meat companies’ databases and the national cattle register for 28,228 calves transported to 87 calf rearing farms. All medications given to these calves were retrospectively followed for 180 days from calf arrival to the farm. In total, 34,532 parenteral antibiotic medications were administered to the 28,228 study calves (122.3%), and 17,180 calves (60.9%) were medicated with antibiotics at least once during the follow-up. Higher numbers of calves transported to the same farm and larger age variation in calves in the same arrival batch were both associated with increased morbidity. In contrast, higher arrival age of individual calves was associated with decreased morbidity. Our study identifies several factors to consider in decreasing morbidity and antibiotic usage on calf rearing farms. Full article

(This article belongs to the Topic Emerging Material-Based Approaches to Chronic and Infectious Diseases)

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16 pages, 6110 KiB

Open AccessArticle

Fenofibrate Nano-Eyedrops Ameliorate Retinal Blood Flow Dysregulation and Neurovascular Coupling in Type 2 Diabetic Mice

by Junya Hanaguri, Noriaki Nagai, Harumasa Yokota, Akifumi Kushiyama, Masahisa Watanabe, Satoru Yamagami and Taiji Nagaoka

Pharmaceutics 2022, 14(2), 384; https://doi.org/10.3390/pharmaceutics14020384 - 9 Feb 2022

Cited by 17 | Viewed by 3426

Abstract

We investigated the effect of fenofibrate nano-eyedrops (FenoNano) on impaired retinal blood flow regulation in type 2 diabetic mice. Six-week-old db/db mice were randomly divided into an untreated group (n = 6) and treated group, which received FenoNano (n = 6). [...] Read more.

We investigated the effect of fenofibrate nano-eyedrops (FenoNano) on impaired retinal blood flow regulation in type 2 diabetic mice. Six-week-old db/db mice were randomly divided into an untreated group (n = 6) and treated group, which received FenoNano (n = 6). The longitudinal changes in retinal neuronal function and blood flow responses to systemic hyperoxia and flicker stimulation were evaluated every 2 weeks in diabetic db/db mice treated with FenoNano (n = 6) or the vehicle (n = 6) from ages 8–14 weeks. The retinal blood flow was assessed using laser speckle flowgraphy. We also evaluated the expressions of vascular endothelial growth factor (VEGF), glial fibrillary acidic protein (GFAP), and aquaporin 4 (AQP4) and the phosphorylation of peroxisome proliferator-activated receptor alpha (PPAR-α) by immunofluorescence. In db/db mice treated with FenoNano, both responses were restored from 8 to 14 weeks of age compared with the diabetic mice treated with the vehicle. At 14 weeks of age, the impaired regulation of retinal blood flow during systemic hyperoxia and flicker stimulation improved to about half of that in the db/db mice treated with FenoNano compared with the db/m control group (n = 5). FenoNano prevented the activation of VEGF and GFAP expression and increased the AQP4 expression and the phosphorylation of PPAR-α detected by immunofluorescence compared with the diabetic mice treated with the vehicle eyedrop. Our results suggested that the fenofibrate nano-eyedrops prevent retinal glial dysfunction via the phosphorylation of PPAR-α and improves the retinal blood flow dysregulation in type 2 diabetic mice. Full article

(This article belongs to the Topic Emerging Material-Based Approaches to Chronic and Infectious Diseases)

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12 pages, 11424 KiB

Open AccessArticle

Photolytic Controlled Release Formulation of Methotrexate Loaded in Chitosan/TiO₂ Nanoparticles for Breast Cancer

by Nusaiba Al-Nemrawi, Fatima Hameedat, Belal Al-Husein and Sukaina Nimrawi

Pharmaceuticals 2022, 15(2), 149; https://doi.org/10.3390/ph15020149 - 26 Jan 2022

Cited by 26 | Viewed by 3751

Abstract

A new system composed of chitosan nanoparticles loaded with methotrexate (MTX-CS-NPs) and functionalized with photocatalytic TiO₂ nanoparticles (TiO₂-NPs) was prepared. This system is expected to initiate polymeric rupture of MTX-CS-NPs and subsequently release MTX, upon illumination with UV light. MTX-CS-NPs [...] Read more.

A new system composed of chitosan nanoparticles loaded with methotrexate (MTX-CS-NPs) and functionalized with photocatalytic TiO₂ nanoparticles (TiO₂-NPs) was prepared. This system is expected to initiate polymeric rupture of MTX-CS-NPs and subsequently release MTX, upon illumination with UV light. MTX-CS-NPs were prepared and characterized in terms of particle size, charge, polydispersity and drug release before and after coating with TiO₂-NPs. The release of MTX in vitro was studied in dark, light and UV light. Finally, coated and uncoated MTX-CS-NPs were studied in vitro using MCF-7 cell line. The functionalized NPs were larger in size, more polydisperse and carried higher positive charges compared to the unfunctionalized NPs. The entrapment efficacy was high reaching 75% and was not affected by coating with MTX-CS-NPs. Further, less than 5% of methotrexate was released after 80 h from uncoated NPs and the release was not enhanced by UV illumination of the particles. In contrast, the release from functionalized NPs was enhanced, reaching 40% after 80 h, as the particles were stroked with UV light and as the amount of TiO₂-NPs used in coating increased. Finally, coating the MTX-CS-NPs with TiO₂-NPs significantly enhanced their cytotoxicity on MCF-7 cells. The coated MTX-CS-NPs recorded low cell viabilities compared to the other formulations. In conclusion, the drug release of MTX-CS-NPs could be triggered and controlled remotely by coating with TiO₂-NPs, which maybe more effective in cancer treatment. Full article

(This article belongs to the Topic Emerging Material-Based Approaches to Chronic and Infectious Diseases)

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20 pages, 4495 KiB

Open AccessEditor’s ChoiceArticle

Superparamagnetic Iron Oxide Nanoparticles Decorated Mesoporous Silica Nanosystem for Combined Antibiofilm Therapy

by Elena Álvarez, Manuel Estévez, Alvaro Gallo-Cordova, Blanca González, Rafael R. Castillo, María del Puerto Morales, Montserrat Colilla, Isabel Izquierdo-Barba and María Vallet-Regí

Pharmaceutics 2022, 14(1), 163; https://doi.org/10.3390/pharmaceutics14010163 - 11 Jan 2022

Cited by 27 | Viewed by 3797

Abstract

A crucial challenge to face in the treatment of biofilm-associated infection is the ability of bacteria to develop resistance to traditional antimicrobial therapies based on the administration of antibiotics alone. This study aims to apply magnetic hyperthermia together with controlled antibiotic delivery from [...] Read more.

A crucial challenge to face in the treatment of biofilm-associated infection is the ability of bacteria to develop resistance to traditional antimicrobial therapies based on the administration of antibiotics alone. This study aims to apply magnetic hyperthermia together with controlled antibiotic delivery from a unique magnetic-responsive nanocarrier for a combination therapy against biofilm. The design of the nanosystem is based on antibiotic-loaded mesoporous silica nanoparticles (MSNs) externally functionalized with a thermo-responsive polymer capping layer, and decorated in the outermost surface with superparamagnetic iron oxide nanoparticles (SPIONs). The SPIONs are able to generate heat upon application of an alternating magnetic field (AMF), reaching the temperature needed to induce a change in the polymer conformation from linear to globular, therefore triggering pore uncapping and the antibiotic cargo release. The microbiological assays indicated that exposure of E. coli biofilms to 200 µg/mL of the nanosystem and the application of an AMF (202 kHz, 30 mT) decreased the number of viable bacteria by 4 log₁₀ units compared with the control. The results of the present study show that combined hyperthermia and antibiotic treatment is a promising approach for the effective management of biofilm-associated infections. Full article

(This article belongs to the Topic Emerging Material-Based Approaches to Chronic and Infectious Diseases)

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14 pages, 520 KiB

Open AccessArticle

A Case-Control of Patients with COVID-19 to Explore the Association of Previous Hospitalisation Use of Medication on the Mortality of COVID-19 Disease: A Propensity Score Matching Analysis

by Jaime Monserrat Villatoro, Gina Mejía-Abril, Lucía Díaz García, Pablo Zubiaur, María Jiménez González, Guillermo Fernandez Jimenez, Inés Cancio, José Ramón Arribas, Carmen Suarez Fernández, Jesús Mingorance, Julio García Rodríguez, José Ramón Villagrasa Ferrer, Antonio J. Carcas, Jesús Frías, Francisco Abad-Santos, Alberto M. Borobia, Elena Ramírez and on behalf of the COVID@HULP Working Group and Other Collaborators from Hospital Universitario de la Princesa

Pharmaceuticals 2022, 15(1), 78; https://doi.org/10.3390/ph15010078 - 8 Jan 2022

Cited by 9 | Viewed by 4563

Abstract

Data from several cohorts of coronavirus disease 2019 (COVID-19) suggest that the most common comorbidities for severe COVID-19 disease are the elderly, high blood pressure, and diabetes; however, it is not currently known whether the previous use of certain drugs help or hinder [...] Read more.

Data from several cohorts of coronavirus disease 2019 (COVID-19) suggest that the most common comorbidities for severe COVID-19 disease are the elderly, high blood pressure, and diabetes; however, it is not currently known whether the previous use of certain drugs help or hinder recovery. This study aims to explore the association of previous hospitalisation use of medication on the mortality of COVID-19 disease. A retrospective case-control from two hospitals in Madrid, Spain, included all patients aged 18 years or above hospitalised with a diagnosis of COVID-19. A Propensity Score matching (PSM) analysis was performed. Confounding variables were considered to be age, sex, and the number of comorbidities. Finally, 3712 patients were included. Of these, 687 (18.5%) patients died (cases). The 22,446 medicine trademarks used previous to admission were classified according to the ATC, obtaining 689 final drugs; all of them were included in PSM analysis. Eleven drugs displayed a reduction in mortality: azithromycin, bemiparine, budesonide-formoterol fumarate, cefuroxime, colchicine, enoxaparin, ipratropium bromide, loratadine, mepyramine theophylline acetate, oral rehydration salts, and salbutamol sulphate. Eight final drugs displayed an increase in mortality: acetylsalicylic acid, digoxin, folic acid, mirtazapine, linagliptin, enalapril, atorvastatin, and allopurinol. Medication associated with survival (anticoagulants, antihistamines, azithromycin, bronchodilators, cefuroxime, colchicine, and inhaled corticosteroids) may be candidates for future clinical trials. Drugs associated with mortality show an interaction with the underlying conditions. Full article

(This article belongs to the Topic Emerging Material-Based Approaches to Chronic and Infectious Diseases)

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15 pages, 3405 KiB

Open AccessArticle

Reverse Iontophoretic Extraction of Skin Cancer-Related Biomarkers

by Maxim Morin, Sebastian Björklund, Skaidre Jankovskaja, Kieran Moore, Maria Begoña Delgado-Charro, Tautgirdas Ruzgas, Richard H. Guy and Johan Engblom

Pharmaceutics 2022, 14(1), 79; https://doi.org/10.3390/pharmaceutics14010079 - 29 Dec 2021

Cited by 5 | Viewed by 2505

Abstract

Non-invasive methods for early diagnosis of skin cancer are highly valued. One possible approach is to monitor relevant biomarkers such as tryptophan (Trp) and kynurenine (Kyn), on the skin surface. The primary aim of this in vitro investigation was, therefore, to examine whether [...] Read more.

Non-invasive methods for early diagnosis of skin cancer are highly valued. One possible approach is to monitor relevant biomarkers such as tryptophan (Trp) and kynurenine (Kyn), on the skin surface. The primary aim of this in vitro investigation was, therefore, to examine whether reverse iontophoresis (RI) can enhance the extraction of Trp and Kyn, and to demonstrate how the Trp/Kyn ratio acquired from the skin surface reflects that in the epidermal tissue. The study also explored whether the pH of the receiver medium impacted on extraction efficiency, and assessed the suitability of a bicontinuous cubic liquid crystal as an alternative to a simple buffer solution for this purpose. RI substantially enhanced the extraction of Trp and Kyn, in particular towards the cathode. The Trp/Kyn ratio obtained on the surface matched that in the viable skin. Increasing the receiver solution pH from 4 to 9 improved extraction of both analytes, but did not significantly change the Trp/Kyn ratio. RI extraction of Trp and Kyn into the cubic liquid crystal was comparable to that achieved with simple aqueous receiver solutions. We conclude that RI offers a potential for non-invasive sampling of low-molecular weight biomarkers and further investigations in vivo are therefore warranted. Full article

(This article belongs to the Topic Emerging Material-Based Approaches to Chronic and Infectious Diseases)

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16 pages, 4845 KiB

Open AccessArticle

Thermosensitive Poly(DHSe/PEG/PPG Urethane)-Based Hydrogel Extended Remdesivir Application in Ophthalmic Medication

by Sennan Xu, Lingjie Ke, Sichen Zhao, Zhiguo Li, Yang Xiao, Yunlong Wu, Jie Ren and Yan Qiu

Pharmaceutics 2022, 14(1), 50; https://doi.org/10.3390/pharmaceutics14010050 - 27 Dec 2021

Cited by 9 | Viewed by 3757

Abstract

The spread of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused the coronavirus disease 2019 (COVID-19) outbreak beginning in March 2020. Currently, there is a lack of suitable dose formulations that interrupt novel coronavirus transmission via corneal and conjunctival routes. In [...] Read more.

The spread of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused the coronavirus disease 2019 (COVID-19) outbreak beginning in March 2020. Currently, there is a lack of suitable dose formulations that interrupt novel coronavirus transmission via corneal and conjunctival routes. In the present study, we developed and evaluated a thermosensitive gelling system based on a selenium-containing polymer for topical ocular continuous drug release. In detail, di-(1-hydroxylundecyl) selenide (DHSe), poly(ethylene glycol) (PEG), and poly(propylene glycol) (PPG) were polymerized to form poly(DHSe/PEG/PPG urethane). The polymer was used to carry poorly water-soluble remdesivir (RDV) at room temperature to form the final thermosensitive in situ gel, which exhibited a typical sol-gel transition at 35 °C. The formed polymer was further characterized by rheology, thermology, and scanning electron microscopy. In vitro release studies and in vivo retention and penetration tests indicated that the thermogel provided the prolonged release of RDV. The RDV-loaded in situ gel was proven to be non-biotoxic against human corneal epithelial cells, with good ocular tolerance and biocompatibility in rabbit eyes. Full article

(This article belongs to the Topic Emerging Material-Based Approaches to Chronic and Infectious Diseases)

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44 pages, 2340 KiB

Open AccessReview

Biomaterial and Therapeutic Approaches for the Manipulation of Macrophage Phenotype in Peripheral and Central Nerve Repair

by Adrian Dervan, Antonio Franchi, Francisco R. Almeida-Gonzalez, Jennifer K. Dowling, Ohemaa B. Kwakyi, Claire E. McCoy, Fergal J. O’Brien and Alan Hibbitts

Pharmaceutics 2021, 13(12), 2161; https://doi.org/10.3390/pharmaceutics13122161 - 15 Dec 2021

Cited by 25 | Viewed by 6705

Abstract

Injury to the peripheral or central nervous systems often results in extensive loss of motor and sensory function that can greatly diminish quality of life. In both cases, macrophage infiltration into the injury site plays an integral role in the host tissue inflammatory [...] Read more.

Injury to the peripheral or central nervous systems often results in extensive loss of motor and sensory function that can greatly diminish quality of life. In both cases, macrophage infiltration into the injury site plays an integral role in the host tissue inflammatory response. In particular, the temporally related transition of macrophage phenotype between the M1/M2 inflammatory/repair states is critical for successful tissue repair. In recent years, biomaterial implants have emerged as a novel approach to bridge lesion sites and provide a growth-inductive environment for regenerating axons. This has more recently seen these two areas of research increasingly intersecting in the creation of ‘immune-modulatory’ biomaterials. These synthetic or naturally derived materials are fabricated to drive macrophages towards a pro-repair phenotype. This review considers the macrophage-mediated inflammatory events that occur following nervous tissue injury and outlines the latest developments in biomaterial-based strategies to influence macrophage phenotype and enhance repair. Full article

(This article belongs to the Topic Emerging Material-Based Approaches to Chronic and Infectious Diseases)

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15 pages, 8481 KiB

Open AccessArticle

Abdominoplasty Skin-Based Dressing for Deep Wound Treatment—Evaluation of Different Methods of Preparation on Therapeutic Potential

by Dawid Groth, Izabela Poplawska, Marlena Tynecka, Kamil Grubczak, Jordan Holl, Aleksandra Starosz, Adrian Janucik, Klaudia Borkowska, Dorota Juchniewicz, Hady Razak Hady, Slawomir Czaban, Joanna Reszec, Artur Kaminski, Tomasz Czech, Cezary Kowalewski, Piotr Fiedor, Zbigniew Zimek, Hanna Lewandowska, Tomasz Oldak, Marcin Moniuszko and Andrzej Eljaszewicz Show full author list Hide full author list

Pharmaceutics 2021, 13(12), 2118; https://doi.org/10.3390/pharmaceutics13122118 - 8 Dec 2021

Cited by 7 | Viewed by 3745

Abstract

The management of hard-to-heal wounds is a significant clinical challenge. Acellular dermal matrices (ADMs) have been successfully introduced to enhance the healing process. Here, we aimed to develop protocol for the preparation of novel ADMs from abdominoplasty skin. We used three different decellularization [...] Read more.

The management of hard-to-heal wounds is a significant clinical challenge. Acellular dermal matrices (ADMs) have been successfully introduced to enhance the healing process. Here, we aimed to develop protocol for the preparation of novel ADMs from abdominoplasty skin. We used three different decellularization protocols for skin processing, namely, 1M NaCl and sodium dodecyl sulfate (SDS, in ADM1); 2M NaCl and sodium dodecyl sulfate (SDS, in ADM1); and a combination of recombinant trypsin and Triton X-100 (in hADM 3). We assessed the effectiveness of decellularization and ADM’s structure by using histochemical and immunochemical staining. In addition, we evaluated the therapeutic potential of novel ADMs in a murine model of wound healing. Furthermore, targeted transcriptomic profiling of genes associated with wound healing was performed. First, we found that all three proposed methods of decellularization effectively removed cellular components from abdominoplasty skin. We showed, however, significant differences in the presence of class I human leukocyte antigen (HLA class I ABC), Talin 1/2, and chondroitin sulfate proteoglycan (NG2). In addition, we found that protocols, when utilized differentially, influenced the preservation of types I, III, IV, and VII collagens. Finally, we showed that abdominoplasty skin-derived ADMs might serve as an effective and safe option for deep wound treatment. More importantly, our novel dressing (ADM1) improves the kinetics of wound closure and scar maturation in the proliferative and remodeling phases of wound healing. In conclusion, we developed a protocol for abdominoplasty skin decellularization suitable for the preparation of biological dressings. We showed that different decellularization methods affect the purity, structure, and therapeutic properties of ADMs. Full article

(This article belongs to the Topic Emerging Material-Based Approaches to Chronic and Infectious Diseases)

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16 pages, 3618 KiB

Open AccessArticle

Assessing the Effects of VEGF Releasing Microspheres on the Angiogenic and Foreign Body Response to a 3D Printed Silicone-Based Macroencapsulation Device

by Ruth E. Levey, Fergal B. Coulter, Karina C. Scheiner, Stefano Deotti, Scott T. Robinson, Liam McDonough, Thanh T. Nguyen, Rob Steendam, Mark Canney, Robert Wylie, Liam P. Burke, Eimear B. Dolan, Peter Dockery, Helena M. Kelly, Giulio Ghersi, Wim E. Hennink, Robbert J. Kok, Eoin O’Cearbhaill and Garry P. Duffy

Pharmaceutics 2021, 13(12), 2077; https://doi.org/10.3390/pharmaceutics13122077 - 4 Dec 2021

Cited by 13 | Viewed by 4324

Abstract

Macroencapsulation systems have been developed to improve islet cell transplantation but can induce a foreign body response (FBR). The development of neovascularization adjacent to the device is vital for the survival of encapsulated islets and is a limitation for long-term device success. Previously [...] Read more.

Macroencapsulation systems have been developed to improve islet cell transplantation but can induce a foreign body response (FBR). The development of neovascularization adjacent to the device is vital for the survival of encapsulated islets and is a limitation for long-term device success. Previously we developed additive manufactured multi-scale porosity implants, which demonstrated a 2.5-fold increase in tissue vascularity and integration surrounding the implant when compared to a non-textured implant. In parallel to this, we have developed poly(ε-caprolactone-PEG-ε-caprolactone)-b-poly(L-lactide) multiblock copolymer microspheres containing VEGF, which exhibited continued release of bioactive VEGF for 4-weeks in vitro. In the present study, we describe the next step towards clinical implementation of an islet macroencapsulation device by combining a multi-scale porosity device with VEGF releasing microspheres in a rodent model to assess prevascularization over a 4-week period. An in vivo estimation of vascular volume showed a significant increase in vascularity (* p = 0.0132) surrounding the +VEGF vs. −VEGF devices, however, histological assessment of blood vessels per area revealed no significant difference. Further histological analysis revealed significant increases in blood vessel stability and maturity (** p = 0.0040) and vessel diameter size (*** p = 0.0002) surrounding the +VEGF devices. We also demonstrate that the addition of VEGF microspheres did not cause a heightened FBR. In conclusion, we demonstrate that the combination of VEGF microspheres with our multi-scale porous macroencapsulation device, can encourage the formation of significantly larger, stable, and mature blood vessels without exacerbating the FBR. Full article

(This article belongs to the Topic Emerging Material-Based Approaches to Chronic and Infectious Diseases)

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18 pages, 4692 KiB

Open AccessArticle

Smart Device for Biologically Enhanced Functional Regeneration of Osteo–Tendon Interface

by Angela Faccendini, Eleonora Bianchi, Marco Ruggeri, Barbara Vigani, Cesare Perotti, Francesco Claudio Pavesi, Laura Caliogna, Francesca Natali, Elena Del Favero, Laura Cantu’, Franca Ferrari, Silvia Rossi and Giuseppina Sandri

Pharmaceutics 2021, 13(12), 1996; https://doi.org/10.3390/pharmaceutics13121996 - 24 Nov 2021

Cited by 10 | Viewed by 2801

Abstract

The spontaneous healing of a tendon laceration results in the formation of scar tissue, which has lower functionality than the original tissue. Moreover, chronic non-healing tendon injuries frequently require surgical treatment. Several types of scaffolds have been developed using the tissue engineering approach, [...] Read more.

The spontaneous healing of a tendon laceration results in the formation of scar tissue, which has lower functionality than the original tissue. Moreover, chronic non-healing tendon injuries frequently require surgical treatment. Several types of scaffolds have been developed using the tissue engineering approach, to complement surgical procedures and to enhance the healing process at the injured site. In this work, an electrospun hybrid tubular scaffold was designed to mimic tissue fibrous arrangement and extracellular matrix (ECM) composition, and to be extemporaneously loaded into the inner cavity with human platelet lysate (PL), with the aim of leading to complete post-surgery functional regeneration of the tissue for functional regeneration of the osteo–tendon interface. For this purpose, pullulan (P)/chitosan (CH) based polymer solutions were enriched with hydroxyapatite nanoparticles (HP) and electrospun. The nanofibers were collected vertically along the length of the scaffold to mimic the fascicle direction of the tendon tissue. The scaffold obtained showed tendon-like mechanical performance, depending on HP content and tube size. The PL proteins were able to cross the scaffold wall, and in vitro studies have demonstrated that tenocytes and osteoblasts are able to adhere to and proliferate onto the scaffold in the presence of PL; moreover, they were also able to produce either collagen or sialoproteins, respectively—important components of ECM. These results suggest that HP and PL have a synergic effect, endorsing PL-loaded HP-doped aligned tubular scaffolds as an effective strategy to support new tissue formation in tendon-to-bone interface regeneration. Full article

(This article belongs to the Topic Emerging Material-Based Approaches to Chronic and Infectious Diseases)

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17 pages, 10887 KiB

Open AccessArticle

Excipient-Free Inhalable Microparticles of Azithromycin Produced by Electrospray: A Novel Approach to Direct Pulmonary Delivery of Antibiotics

by Beatriz Arauzo, Tania B. Lopez-Mendez, Maria Pilar Lobera, Javier Calzada-Funes, Jose Luis Pedraz and Jesus Santamaria

Pharmaceutics 2021, 13(12), 1988; https://doi.org/10.3390/pharmaceutics13121988 - 23 Nov 2021

Cited by 6 | Viewed by 3941

Abstract

Inhalation therapy offers several advantages in respiratory disease treatment. Azithromycin is a macrolide antibiotic with poor solubility and bioavailability but with a high potential to be used to fight lung infections. The main objective of this study was to generate a new inhalable [...] Read more.

Inhalation therapy offers several advantages in respiratory disease treatment. Azithromycin is a macrolide antibiotic with poor solubility and bioavailability but with a high potential to be used to fight lung infections. The main objective of this study was to generate a new inhalable dry powder azithromycin formulation. To this end, an electrospray was used, yielding a particle size around 2.5 µm, which is considered suitable to achieve total deposition in the respiratory system. The physicochemical properties and morphology of the obtained microparticles were analysed with a battery of characterization techniques. In vitro deposition assays were evaluated after aerosolization of the powder at constant flow rate (100 L/min) and the consideration of the simulation of two different realistic breathing profiles (healthy and chronic obstructive pulmonary disease (COPD) patients) into a next generation impactor (NGI). The formulation was effective in vitro against two types of bacteria, Staphylococcus aureus and Pseudomonas aeruginosa. Finally, the particles were biocompatible, as evidenced by tests on the alveolar cell line (A549) and bronchial cell line (Calu-3). Full article

(This article belongs to the Topic Emerging Material-Based Approaches to Chronic and Infectious Diseases)

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21 pages, 39562 KiB

Open AccessArticle

Ceragenin-Coated Non-Spherical Gold Nanoparticles as Novel Candidacidal Agents

by Karol Skłodowski, Sylwia Joanna Chmielewska, Joanna Depciuch, Piotr Deptuła, Ewelina Piktel, Tamara Daniluk, Magdalena Zakrzewska, Michał Czarnowski, Mateusz Cieśluk, Bonita Durnaś, Magdalena Parlińska-Wojtan, Paul B. Savage and Robert Bucki

Pharmaceutics 2021, 13(11), 1940; https://doi.org/10.3390/pharmaceutics13111940 - 16 Nov 2021

Cited by 9 | Viewed by 2754

Abstract

Background: Infections caused by Candida spp. have become one of the major causes of morbidity and mortality in immunocompromised patients. Therefore, new effective fungicides are urgently needed, especially due to an escalating resistance crisis. Methods: A set of nanosystems with rod- (AuR), peanut- [...] Read more.

Background: Infections caused by Candida spp. have become one of the major causes of morbidity and mortality in immunocompromised patients. Therefore, new effective fungicides are urgently needed, especially due to an escalating resistance crisis. Methods: A set of nanosystems with rod- (AuR), peanut- (AuP), and star-shaped (AuS) metal cores were synthesized. These gold nanoparticles were conjugated with ceragenins CSA-13, CSA-44, and CSA-131, and their activity was evaluated against Candida strains (n = 21) through the assessment of MICs (minimum inhibitory concentrations)/MFCs (minimum fungicidal concentrations). Moreover, in order to determine the potential for resistance development, serial passages of Candida cells with tested nanosystems were performed. The principal mechanism of action of Au NPs was evaluated via ROS (reactive oxygen species) generation assessment, plasma membrane permeabilization, and release of the protein content. Finally, to evaluate the potential toxicity of Au NPs, the measurement of hemoglobin release from red blood cells (RBCs) was carried out. Results: All of the tested nanosystems exerted a potent candidacidal activity, regardless of the species or susceptibility to other antifungal agents. Significantly, no resistance development after 25 passages of Candida cells with AuR@CSA-13, AuR@CSA-44, and AuR@CSA-131 nanosystems was observed. Moreover, the fungicidal mechanism of action of the investigated nanosystems involved the generation of ROS, damage of the fungal cell membrane, and leakage of intracellular contents. Notably, no significant RBCs hemolysis at candidacidal doses of tested nanosystems was detected. Conclusions: The results provide rationale for the development of gold nanoparticles of rod-, peanut-, and star-shaped conjugated with CSA-13, CSA-44, and CSA-131 as effective candidacidal agents. Full article

(This article belongs to the Topic Emerging Material-Based Approaches to Chronic and Infectious Diseases)

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15 pages, 1824 KiB

Open AccessArticle

Lipid Nanoparticles Loaded with Farnesol or Geraniol to Enhance the Susceptibility of E. coli MCR-1 to Colistin

by Chantal Valcourt, Julien M. Buyck, Nicolas Grégoire, William Couet, Sandrine Marchand and Frédéric Tewes

Pharmaceutics 2021, 13(11), 1849; https://doi.org/10.3390/pharmaceutics13111849 - 3 Nov 2021

Cited by 7 | Viewed by 2601

Abstract

Resistance to colistin, one of the antibiotics of last resort against multidrug-resistant Gram-negative bacteria, is increasingly reported. Notably, MCR plasmids discovered in 2015 have now been reported worldwide in humans. To keep this antibiotic of last resort efficient, a way to tackle this [...] Read more.

Resistance to colistin, one of the antibiotics of last resort against multidrug-resistant Gram-negative bacteria, is increasingly reported. Notably, MCR plasmids discovered in 2015 have now been reported worldwide in humans. To keep this antibiotic of last resort efficient, a way to tackle this mechanism seems essential. Terpene alcohols such as farnesol have been shown to improve the efficacy of some antibiotics. However, their high lipophilicity makes them difficult to use. This problem can be solved by encapsulating them in water-dispersible lipid nanoparticles (LNPs). The aim of this study was to discover, using checkerboard tests and time-kill curve experiments, an association between colistin and farnesol or geraniol loaded in LNPs, which would improve the efficacy of colistin against E. coli and, in particular, MCR-1 transconjugants. Then, the effect of the combination on E. coli inner membrane permeabilisation was evaluated using propidium iodide (PI) uptake and compared to human red blood cells plasma membrane permeabilisation. Both terpene alcohols were able to restore the susceptibility of E. coli J53 MCR-1 to colistin with the same efficacy (E_max = 16, i.e., colistin MIC was decreased from 8 to 0.5 mg/L). However, with an EC₅₀ of 2.69 mg/L, farnesol was more potent than geraniol (EC₅₀ = 39.49 mg/L). Time-kill studies showed a bactericidal effect on MCR-1 transconjugant 6 h after incubation, with no regrowth up to 30 h in the presence of 1 mg/L colistin (1/8 MIC) and 60 mg/L or 200 mg/L farnesol or geraniol, respectively. Colistin alone was more potent in increasing PI uptake rate in the susceptible strain (EC₅₀ = 0.86 ± 0.08 mg/L) than in the MCR-1 one (EC₅₀ = 7.38 ± 0.85 mg/L). Against the MCR-1 strain, farnesol-loaded LNP at 60 mg/L enhanced the colistin-induced inner membrane permeabilization effect up to 5-fold and also increased its potency as shown by the decrease in its EC₅₀ from 7.38 ± 0.85 mg/L to 2.69 ± 0.25 mg/L. Importantly, no hemolysis was observed for LNPs loaded with farnesol or geraniol, alone or in combination with colistin, at the concentrations showing the maximum decrease in colistin MICs. The results presented here indicate that farnesol-loaded LNPs should be studied as combination therapy with colistin to prevent the development of resistance to this antibiotic of last resort. Full article

(This article belongs to the Topic Emerging Material-Based Approaches to Chronic and Infectious Diseases)

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17 pages, 7725 KiB

Open AccessArticle

Improving the Efficacy of Antimicrobials against Biofilm-Embedded Bacteria Using Bovine Hyaluronidase Azoximer (Longidaza^®)

by Elena Trizna, Diana Baidamshina, Anna Gorshkova, Valentin Drucker, Mikhail Bogachev, Anton Tikhonov and Airat Kayumov

Pharmaceutics 2021, 13(11), 1740; https://doi.org/10.3390/pharmaceutics13111740 - 20 Oct 2021

Cited by 8 | Viewed by 3378

Abstract

While in a biofilm, bacteria are extremely resistant to both antimicrobials and the immune system, leading to the development of chronic infection. Here, we show that bovine hyaluronidase fused with a copolymer of 1,4-ethylenepiperazine N-oxide and (N-carboxymethyl) -1,4-ethylenepiperazinium bromide (Longidaza^®) destroys [...] Read more.

While in a biofilm, bacteria are extremely resistant to both antimicrobials and the immune system, leading to the development of chronic infection. Here, we show that bovine hyaluronidase fused with a copolymer of 1,4-ethylenepiperazine N-oxide and (N-carboxymethyl) -1,4-ethylenepiperazinium bromide (Longidaza^®) destroys both mono- and dual-species biofilms formed by various bacteria. After 4 h of treatment with 750 units of the enzyme, the residual biofilms of Staphylococcus aureus, Enterococcus faecalis, Escherichia coli, Pseudomonas aeruginosa and Klebsiella pneumoniae preserved about 50–70% of their initial mass. Biomasses of dual-species biofilms formed by S. aureus and the four latter species were reduced 1.5-fold after 24 h treatment, while the significant destruction of S. aureus–P. aeruginosa and S. aureus–K. pneumoniae was also observed after 4 h of treatment with Longidaza^®. Furthermore, when applied in combination, Longidaza^® increased the efficacy of various antimicrobials against biofilm-embedded bacteria, although with various increase-factor values depending on both the bacterial species and antimicrobials chosen. Taken together, our data indicate that Longidaza^® destroys the biofilm structure, facilitating the penetration of antimicrobials through the biofilm, and in this way improving their efficacy, lowering the required dose and thus also potentially reducing the associated side effects. Full article

(This article belongs to the Topic Emerging Material-Based Approaches to Chronic and Infectious Diseases)

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50 pages, 3101 KiB

Open AccessReview

Functionalized Nanoparticles Targeting Tumor-Associated Macrophages as Cancer Therapy

by Yuanyuan He, Raimundo Fernandes de Araújo Júnior, Luis J. Cruz and Christina Eich

Pharmaceutics 2021, 13(10), 1670; https://doi.org/10.3390/pharmaceutics13101670 - 13 Oct 2021

Cited by 45 | Viewed by 6174

Abstract

The tumor microenvironment (TME) plays a central role in regulating antitumor immune responses. As an important part of the TME, alternatively activated type 2 (M2) macrophages drive the development of primary and secondary tumors by promoting tumor cell proliferation, tumor angiogenesis, extracellular matrix [...] Read more.

The tumor microenvironment (TME) plays a central role in regulating antitumor immune responses. As an important part of the TME, alternatively activated type 2 (M2) macrophages drive the development of primary and secondary tumors by promoting tumor cell proliferation, tumor angiogenesis, extracellular matrix remodeling and overall immunosuppression. Immunotherapy approaches targeting tumor-associated macrophages (TAMs) in order to reduce the immunosuppressive state in the TME have received great attention. Although these methods hold great potential for the treatment of several cancers, they also face some limitations, such as the fast degradation rate of drugs and drug-induced cytotoxicity of organs and tissues. Nanomedicine formulations that prevent TAM signaling and recruitment to the TME or deplete M2 TAMs to reduce tumor growth and metastasis represent encouraging novel strategies in cancer therapy. They allow the specific delivery of antitumor drugs to the tumor area, thereby reducing side effects associated with systemic application. In this review, we give an overview of TAM biology and the current state of nanomedicines that target M2 macrophages in the course of cancer immunotherapy, with a specific focus on nanoparticles (NPs). We summarize how different types of NPs target M2 TAMs, and how the physicochemical properties of NPs (size, shape, charge and targeting ligands) influence NP uptake by TAMs in vitro and in vivo in the TME. Furthermore, we provide a comparative analysis of passive and active NP-based TAM-targeting strategies and discuss their therapeutic potential. Full article

(This article belongs to the Topic Emerging Material-Based Approaches to Chronic and Infectious Diseases)

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14 pages, 2167 KiB

Open AccessArticle

Daily Administered Dual-Light Photodynamic Therapy Provides a Sustained Antibacterial Effect on Staphylococcus aureus

by Sakari Nikinmaa, Anna Podonyi, Peter Raivio, Jukka Meurman, Timo Sorsa, Juha Rantala, Esko Kankuri, Tuomas Tauriainen and Tommi Pätilä

Antibiotics 2021, 10(10), 1240; https://doi.org/10.3390/antibiotics10101240 - 13 Oct 2021

Cited by 5 | Viewed by 4299

Abstract

New means to reduce excessive antibiotic use are urgently needed. This study tested dual-light aPDT against Staphylococcus aureus biofilm with different relative ratios of light energy with indocyanine green. We applied single-light aPDT (810 nm aPDT, 405 aBL) or dual-light aPDT (simultaneous 810 [...] Read more.

New means to reduce excessive antibiotic use are urgently needed. This study tested dual-light aPDT against Staphylococcus aureus biofilm with different relative ratios of light energy with indocyanine green. We applied single-light aPDT (810 nm aPDT, 405 aBL) or dual-light aPDT (simultaneous 810 nm aPDT and 405 nm aBL), in both cases, together with the ICG photosensitizer with constant energy of 100 or 200 J/cm². Single-dose light exposures were given after one-day, three-day, or six-day biofilm incubations. A repeated daily dose of identical light energy was applied during biofilm incubations for the three- and six-day biofilms. Using 100 J/cm² light energy against the one-day biofilm, the dual-light aPDT consisting of more than half of aBL was the most effective. On a three-day maturated biofilm, single-dose exposure to aPDT or dual-light aPDT was more effective than aBL alone. With total light energy of 200 J/cm², all dual-light treatments were effective. Dual-light aPDT improves the bactericidal effect on Staphylococcus aureus biofilm compared to aPDT or aBL and provides a sustained effect. An increase in the relative ratio of aBL strengthens the antibacterial effect, mainly when the treatment is repeatedly applied. Thus, the light components’ energy ratio is essential with dual-light. Full article

(This article belongs to the Topic Emerging Material-Based Approaches to Chronic and Infectious Diseases)

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