Pharmaceuticals

29 pages, 1029 KiB

Open AccessReview

Review of Intranasal Active Pharmaceutical Ingredient Delivery Systems

by Ruslan Safarov, Olga Fedotova, Anastasia Uvarova, Mariia Gordienko and Natalia Menshutina

Pharmaceuticals 2024, 17(9), 1180; https://doi.org/10.3390/ph17091180 (registering DOI) - 7 Sep 2024

In recent decades, there has been an increased interest in the development of intranasal delivery systems for active pharmaceutical ingredients (APIs) not only for treating local nasal diseases but also for treating systemic diseases, central nervous system (CNS) disorders, and vaccine delivery. The [...] Read more.

In recent decades, there has been an increased interest in the development of intranasal delivery systems for active pharmaceutical ingredients (APIs) not only for treating local nasal diseases but also for treating systemic diseases, central nervous system (CNS) disorders, and vaccine delivery. The nasal cavity possesses a unique set of anatomical characteristics for delivering active pharmaceutical ingredients, but there are several limitations that recent research in the field of the intranasal administration of APIs aims to overcome. For the effective delivery of nasal preparations, active pharmaceutical ingredients are incorporated into various micro- and nanosystems. Some of the most commonly encountered API delivery systems in the scientific literature include liposomal systems, polymer particles with mucoadhesive properties, in situ gels, nano- and microemulsions, and solid lipid particles. This article provides a review of research on the development of nasal preparations for treating local nasal cavity diseases (in particular, for antibiotic delivery), systemic diseases (analgesics, drugs for cardiovascular diseases, antiviral and antiemetic drugs), CNS disorders (Alzheimer’s disease, Parkinson’s disease, epilepsy, schizophrenia, depression), and vaccine delivery. The literature data show that active research is underway to reformulate drugs of various pharmacotherapeutic groups into a nasal form. Full article

(This article belongs to the Section Pharmaceutical Technology)

18 pages, 1009 KiB

Open AccessArticle

Analgesic Effect of Human Placenta Hydrolysate on CFA-Induced Inflammatory Pain in Mice

by Keun-Tae Park, Heejoon Jo, So-Hyun Jeon, Kyeongsoo Jeong, Minju Im, Jae-Won Kim, Jong-Pil Jung, Hoe Chang Jung, Jae hun Lee and Woojin Kim

Pharmaceuticals 2024, 17(9), 1179; https://doi.org/10.3390/ph17091179 (registering DOI) - 7 Sep 2024

Abstract

To evaluate the efficacy of human placenta hydrolysate (HPH) in a mice model of CFA-induced inflammatory pain. TNF-α, IL-1β, and IL-6 are key pro-inflammatory cytokine factors for relieving inflammatory pain. Therefore, this study investigates whether HPH suppresses CFA-induced pain and attenuates the inflammatory [...] Read more.

To evaluate the efficacy of human placenta hydrolysate (HPH) in a mice model of CFA-induced inflammatory pain. TNF-α, IL-1β, and IL-6 are key pro-inflammatory cytokine factors for relieving inflammatory pain. Therefore, this study investigates whether HPH suppresses CFA-induced pain and attenuates the inflammatory process by regulating cytokines. In addition, the relationship between neuropathic pain and HPH was established by staining GFAP and Iba-1 in mice spinal cord tissues. This study was conducted for a total of day 28, and inflammatory pain was induced in mice by injecting CFA into the right paw at day 0 and day 14, respectively. 100 μL of 20% glucose and polydeoxyribonucleotide (PDRN) and 100, 200, and 300 μL of HPH were administered intraperitoneally twice a week. In the CFA-induced group, cold and mechanical allodynia and pro-inflammatory cytokine factors in the spinal cord and plantar tissue were significantly increased. The five groups of drugs evenly reduced pain and gene expression of inflammatory factors, and particularly excellent effects were confirmed in the HPH 200 and 300 groups. Meanwhile, the expression of GFAP and Iba-1 in the spinal cord was increased by CFA administration but decreased by HPH administration, which was confirmed to suppress damage to peripheral ganglia. The present study suggests that HPH attenuates CFA-induced inflammatory pain through inhibition of pro-inflammatory cytokine factors and protection of peripheral nerves. Full article

(This article belongs to the Topic New Compounds Discovery and Development in Medicine — Advances in Research on Potential Therapeutic Agents and Drug Candidates, 2nd Edition)

17 pages, 874 KiB

Open AccessArticle

Methanolic Extract of Rhizophora mangle (Rhizophoraceae) Leaves: Phytochemical Characterization and Anthelmintic Evaluation against Schistosoma mansoni

by Wilza W. M. França, Sérgio D. Magalhães Filho, Lucas A. O. Cavalcante, Mary A. A. S. Gomes, Maria T. V. Gonçalves, Emily G. M. Diniz, Wheverton R. C. Nascimento, Reginaldo G. Lima Neto, Mônica C. P. A. Albuquerque, Iranildo J. Cruz Filho, Hallysson D. A. Araújo, André L. Aires and Jeymesson R. C. Vieira

Pharmaceuticals 2024, 17(9), 1178; https://doi.org/10.3390/ph17091178 - 6 Sep 2024

Abstract

Rhizophora mangle is commonly used in traditional medicine to treat infections, reduce inflammation, and promote healing. This study aimed to analyze the phytochemical profile of the methanolic extract of R. mangle leaves (MELRm) and evaluate its in vitro schistosomicidal activity against Schistosoma mansoni [...] Read more.

Rhizophora mangle is commonly used in traditional medicine to treat infections, reduce inflammation, and promote healing. This study aimed to analyze the phytochemical profile of the methanolic extract of R. mangle leaves (MELRm) and evaluate its in vitro schistosomicidal activity against Schistosoma mansoni as well as its cytotoxicity. Plant material was collected in Itamaracá City, Pernambuco, Brazil. The extract was analyzed using UV/Vis spectrophotometry and high-performance liquid chromatography (HPLC). The motility, mortality, and cell viability of adult worms were assessed in a schistosomicidal assay, while cytotoxicity was evaluated through a colorimetric assay with MTT on RAW 264.7 cells. The primary compounds identified in MELRm were phenolic compounds. In the schistosomicidal assay, all concentrations of MELRs induced changes in the motility of adult worms. At a concentration of 400 μg/mL, MELRs resulted in 56.25% mortality after 72 h of incubation. After 120 h, mortality rates of 75%, 62.5%, and 50% were observed at MELRm concentrations of 400, 200, and 100 μg/mL, respectively. No eggs were detected at any MELRm concentration. MELRs did not show cytotoxicity towards RAW 264.7 cells at the concentrations tested. These results indicate that MELRs demonstrate schistosomicidal activity in vitro, suggesting they are promising candidates for in vivo studies. Full article

18 pages, 6943 KiB

Open AccessArticle

Dual Chemotherapeutic Loading in Oxalate Transferrin-Conjugated Polymersomes Incorporated into Chitosan Hydrogels for Site-Specific Targeting of Melanoma Cells

by Mariana de C. Aranha, Luciana M. R. Alencar, Eliana B. Souto, Daniel T. Kamei and André M. Lopes

Pharmaceuticals 2024, 17(9), 1177; https://doi.org/10.3390/ph17091177 - 6 Sep 2024

Abstract

In this work, we developed a smart drug delivery system composed of poly (ethylene glycol)-block-poly (ε-caprolactone) (PEG-PCL)-based polymersomes (Ps) loaded with doxorubicin (DOX) and vemurafenib (VEM). To enhance targeted delivery to malignant melanoma cells, these drug-loaded nanovesicles were conjugated to the [...] Read more.

In this work, we developed a smart drug delivery system composed of poly (ethylene glycol)-block-poly (ε-caprolactone) (PEG-PCL)-based polymersomes (Ps) loaded with doxorubicin (DOX) and vemurafenib (VEM). To enhance targeted delivery to malignant melanoma cells, these drug-loaded nanovesicles were conjugated to the oxalate transferrin variant (oxalate Tf) and incorporated into three-dimensional chitosan hydrogels. This innovative approach represents the first application of oxalate Tf for the precision delivery of drug-loaded polymersomes within a semi-solid dosage form based on chitosan hydrogels. These resulting semi-solids exhibited a sustained release profile for both encapsulated drugs. To evaluate their potency, we compared the cytotoxicity of native Tf-Ps with oxalate Tf-Ps. Notably, the oxalate Tf-Ps demonstrated a 3-fold decrease in cell viability against melanoma cells compared to normal cells and were 1.6-fold more potent than native Tf-Ps, indicating the greater potency of this nanoformulation. These findings suggest that dual-drug delivery using an oxalate-Tf-targeting ligand significantly enhances the drug delivery efficiency of Tf-conjugated nanovesicles and offers a promising strategy to overcome the challenge of multidrug resistance in melanoma therapy. Full article

(This article belongs to the Special Issue Self-Assembling Nanostructures for Cancer Therapy)

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41 pages, 3878 KiB

Open AccessReview

Insights from Traditional Chinese Medicine for Restoring Skin Barrier Functions

by Jieyi Yang, Jiageng Guo, Peiling Tang, Shidu Yan, Xiaodong Wang, Huaying Li, Jinling Xie, Jiagang Deng, Xiaotao Hou, Zhengcai Du and Erwei Hao

Pharmaceuticals 2024, 17(9), 1176; https://doi.org/10.3390/ph17091176 - 5 Sep 2024

Abstract

The skin barrier is essential for maintaining the body’s internal homeostasis, protecting against harmful external substances, and regulating water and electrolyte balance. Traditional Chinese Medicine (TCM) offers notable advantages in restoring skin barrier function due to its diverse components, targets, and pathways. Recent [...] Read more.

The skin barrier is essential for maintaining the body’s internal homeostasis, protecting against harmful external substances, and regulating water and electrolyte balance. Traditional Chinese Medicine (TCM) offers notable advantages in restoring skin barrier function due to its diverse components, targets, and pathways. Recent studies have demonstrated that active ingredients in TCM can safely and effectively repair damaged skin barriers, reinstating their proper functions. This review article provides a comprehensive overview of the mechanisms underlying skin barrier damage and explores how the bioactive constituents of TCM contribute to skin barrier repair, thereby offering a theoretical framework to inform clinical practices. Full article

(This article belongs to the Section Natural Products)

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15 pages, 8278 KiB

Open AccessArticle

Ferulic Acid Alleviates Radiation-Induced Immune Damage by Acting on JAK/STAT Signaling Pathway

by Mingyue Huang, Anping Ye, Haoyu Zhang, Junru Chen, Tingyu Yang, Xue Wei, Yue Gao and Zengchun Ma

Pharmaceuticals 2024, 17(9), 1175; https://doi.org/10.3390/ph17091175 - 5 Sep 2024

Abstract

The disruption of hematopoietic and immune functions is a significant consequence of the long-term effects of radiation exposure. This study investigated the potential mechanisms by which ferulic acid (FA) acts as a radioprotective agent in mitigating radiation-induced immune damage. C57BL/6J mice were exposed [...] Read more.

The disruption of hematopoietic and immune functions is a significant consequence of the long-term effects of radiation exposure. This study investigated the potential mechanisms by which ferulic acid (FA) acts as a radioprotective agent in mitigating radiation-induced immune damage. C57BL/6J mice were exposed to a dose of 6.0 Gy of ⁶⁰Co γ irradiation. FA was administered at doses of 25, 50, and 100 mg/kg/d for 7 days before and 30 days following irradiation. We evaluated changes in peripheral blood cells, T and B lymphocytes, natural killer cells in the spleen, and hematopoietic stem/progenitor cells in the bone marrow (BM). Whole-genome transcriptome sequencing of BM was performed to explore potential mechanisms. FA administration resulted in a significant reduction in malonaldehyde levels (p < 0.0001), an increase in catalase and beta-nicotinamide adenine dinucleotide levels in serum (p < 0.05), and enhanced multipotent progenitors (p < 0.01) and common lymphoid progenitors (p < 0.05) in the BM. Additionally, there was an elevation in white blood cell levels, red blood cell levels, and hemoglobin levels in peripheral blood (p < 0.01). Transcriptome analysis indicated that FA reversed the radiation-induced expression of genes related to immunity and inflammation. Enzyme-linked immunosorbent assay experiments further demonstrated that FA reduced interleukin-6 levels in the BM and decreased JAK1, JAK2, and STAT3 protein content (p < 0.01). In conclusion, FA might mitigate hematopoietic and immune damage by modulating the JAK/STAT signaling pathway. Full article

(This article belongs to the Section Pharmacology)

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11 pages, 5273 KiB

Open AccessReview

Gabapentin-Induced Adrenal Insufficiency: The Hypothalamic-Pituitary-Adrenal Axis Stress Misresponse and Risk of Infection: A Case Report and Literature Review

by Evmorfia Pechlivanidou, Alexandros Chatzikyriakos, Maria Anna Zisi, Nikolaos Paraskevopoulos, Semeli Kaltsa, Orestis K. Konstantas, Panteleimon Zogakis, Aikaterini Catsouli, Nick Sekouris and Rodanthi E. Margariti

Pharmaceuticals 2024, 17(9), 1174; https://doi.org/10.3390/ph17091174 - 5 Sep 2024

Abstract

This literature review, in light of the presented case report, explores the complex interplay between gabapentin (GBP), a gamma-aminobutyric acid (GABA) analog, and the hypothalamic–pituitary–adrenal (HPA) axis in patients undergoing major surgical procedures. It specifically investigates the potential impact of GBP on cortisol [...] Read more.

This literature review, in light of the presented case report, explores the complex interplay between gabapentin (GBP), a gamma-aminobutyric acid (GABA) analog, and the hypothalamic–pituitary–adrenal (HPA) axis in patients undergoing major surgical procedures. It specifically investigates the potential impact of GBP on cortisol levels, stress responses, and infection risk, illustrated by a detailed clinical case. This review combines a comprehensive literature search with a case report of a 17-year-old male with osteosarcoma who experienced transient adrenal insufficiency and infections while receiving GBP. The case is analyzed in the context of the existing literature on GBP and the HPA axis. The findings highlight the intricate relationship between GBP use, adrenal insufficiency, and infection susceptibility. It underscores the need for further research and clinical vigilance when prescribing GBP to patients with underlying medical conditions, particularly in the context of major surgical procedures. The review underscores the need for further research and clinical vigilance when prescribing GBP, particularly in perioperative settings. In conclusion, GBP’s effects on the HPA axis and immune responses are complex and multifaceted. Clinicians should exercise caution when prescribing GBP, especially for patients with underlying conditions undergoing major surgery. Further research is needed to elucidate the mechanisms of GBP’s influence on cortisol levels and stress responses. Full article

(This article belongs to the Section Pharmacology)

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13 pages, 1829 KiB

Open AccessArticle

Anti-Amnesic Effect of Agastache rugosa on Scopolamine-Induced Memory Impairment in Mice

by Sohi Kang, Nari Lee, Bokyung Jung, Huiyeong Jeong, Changjong Moon, Sang-Ik Park, Seungpil Yun, Teresa Yim, Jung Min Oh, Jae-Won Kim, Ji Hoon Song, Sungwook Chae and Joong Sun Kim

Pharmaceuticals 2024, 17(9), 1173; https://doi.org/10.3390/ph17091173 - 5 Sep 2024

Abstract

Agastache rugosa, a traditional Asian herbal medicine, is primarily used for digestive problems; yet, its cognitive benefits remain unexplored. This study evaluated the anti-amnesic effects of A. rugosa extract (ARE) on scopolamine (SCO)-induced memory impairment in mice. Mice received 100 or 200 [...] Read more.

Agastache rugosa, a traditional Asian herbal medicine, is primarily used for digestive problems; yet, its cognitive benefits remain unexplored. This study evaluated the anti-amnesic effects of A. rugosa extract (ARE) on scopolamine (SCO)-induced memory impairment in mice. Mice received 100 or 200 mg/kg ARE orally for 5 days, followed by SCO injection. The ARE demonstrated significant antioxidant (DPPH IC₅₀: 75.3 µg/mL) and anti-inflammatory effects (NO reduction). Furthermore, the ARE significantly improved memory performance in the passive avoidance test (escape latency: 157.2 s vs. 536.9 s), the novel object recognition test (novel object preference: 47.6% vs. 66.3%) and the Morris water maze (time spent in the target quadrant: 30.0% vs. 45.1%). The ARE reduced hippocampal acetylcholinesterase activity (1.8-fold vs. 1.1-fold) while increasing choline acetyltransferase (0.4-fold vs. 1.0-fold) and muscarinic acetylcholine receptor subtype I (0.3-fold vs. 1.6-fold) expression. The ARE improved hippocampal neurogenesis via doublecortin- (0.4-fold vs. 1.1-fold) and KI-67-positive (6.3 vs. 12.0) cells. Therefore, the ARE exerts protective effects against cognitive decline through cholinergic system modulation and antioxidant activity, supporting its potential use as a cognitive enhancer. Full article

(This article belongs to the Section Biopharmaceuticals)

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1 pages, 147 KiB

Open AccessCorrection

Correction: Belal et al. Therapeutic Potential of Zeolites/Vitamin B12 Nanocomposite on Complete Freund’s Adjuvant-Induced Arthritis as a Bone Disorder: In Vivo Study and Bio-Molecular Investigations. Pharmaceuticals2023, 16, 285

by Amany Belal, Rehab Mahmoud, Mohamed Taha, Fatma Mohamed Halfaya, Ahmed Hassaballa, Esraa Salah Elbanna, Esraa Khaled, Ahmed Farghali, Fatma I. Abo El-Ela, Samar M. Mahgoub, Mohammed M. Ghoneim and Mohamed Y. Zaky

Pharmaceuticals 2024, 17(9), 1172; https://doi.org/10.3390/ph17091172 - 5 Sep 2024

Abstract

In the original publication [...] Full article

24 pages, 3471 KiB

Open AccessArticle

Novel Pyrrole Derivatives as Multi-Target Agents for the Treatment of Alzheimer’s Disease: Microwave-Assisted Synthesis, In Silico Studies and Biological Evaluation

by Emilio Mateev, Valentin Karatchobanov, Marjano Dedja, Konstantinos Diamantakos, Alexandrina Mateeva, Muhammed Tilahun Muhammed, Ali Irfan, Magdalena Kondeva-Burdina, Iva Valkova, Maya Georgieva and Alexander Zlatkov

Pharmaceuticals 2024, 17(9), 1171; https://doi.org/10.3390/ph17091171 - 4 Sep 2024

Abstract

Considering the complex pathogenesis of Alzheimer’s disease (AD), the multi-target ligand strategy is expected to provide superior effects for the treatment of the neurological disease compared to the classic single target strategy. Thus, one novel pyrrole-based hydrazide (vh0) and four corresponding [...] Read more.

Considering the complex pathogenesis of Alzheimer’s disease (AD), the multi-target ligand strategy is expected to provide superior effects for the treatment of the neurological disease compared to the classic single target strategy. Thus, one novel pyrrole-based hydrazide (vh0) and four corresponding hydrazide–hydrazones (vh1-4) were synthesized by applying highly efficient MW-assisted synthetic protocols. The synthetic pathway provided excellent yields and reduced reaction times under microwave conditions compared to conventional heating. The biological assays indicated that most of the novel pyrroles are selective MAO-B inhibitors with IC₅₀ in the nanomolar range (665 nM) and moderate AChE inhibitors. The best dual-acting MAO-B/AChE inhibitor (IC₅₀ hMAOB–0.665 μM; IC₅₀ eeAChE—4.145 μM) was the unsubstituted pyrrole-based hydrazide (vh0). Importantly, none of the novel molecules displayed hMAOA-blocking capacities. The radical-scavenging properties of the compounds were examined using DPPH and ABTS in vitro tests. Notably, the hydrazide vh0 demonstrated the best antioxidant activities. In addition, in silico simulations using molecular docking and MM/GBSA, targeting the AChE (PDB ID: 4EY6) and MAO-B (PDB: 2V5Z), were utilized to obtain active conformations and to optimize the most prominent dual inhibitor (vh0). The ADME and in vitro PAMPA studies demonstrated that vh0 could cross the blood–brain barrier, and it poses good lead-like properties. Moreover, the optimized molecular structures and the frontier molecular orbitals were examined via DFT studies at 6-311G basis set in the ground state. Full article

(This article belongs to the Special Issue Pharmacotherapy of Neurodegeneration Disorders)

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16 pages, 4396 KiB

Open AccessArticle

Study on the Therapeutic Effects and Mechanisms of Gintonin in Irritable Bowel Syndrome and Its Relationship with TRPV1, TRPV4, and NaV1.5

by Na-Ri Choi, Seok-Jae Ko, Joo-Hyun Nam, Woo-Gyun Choi, Jong-Hwan Lee, Seung-Yeol Nah, Jae-Woo Park and Byung-Joo Kim

Pharmaceuticals 2024, 17(9), 1170; https://doi.org/10.3390/ph17091170 - 4 Sep 2024

Abstract

Irritable bowel syndrome (IBS) is a gastrointestinal (GI) disease accompanied by changes in bowel habits without any specific cause. Gintonin is a newly isolated glycoprotein from ginseng that is a lysophosphatidic acid (LPA) receptor ligand. To investigate the efficacy and mechanisms of action [...] Read more.

Irritable bowel syndrome (IBS) is a gastrointestinal (GI) disease accompanied by changes in bowel habits without any specific cause. Gintonin is a newly isolated glycoprotein from ginseng that is a lysophosphatidic acid (LPA) receptor ligand. To investigate the efficacy and mechanisms of action of gintonin in IBS, we developed a zymosan-induced IBS murine model. In addition, electrophysiological experiments were conducted to confirm the relevance of various ion channels. In mice, gintonin restored colon length and weight to normal and decreased stool scores, whilst food intake remained constant. Colon mucosal thickness and inflammation-related tumor necrosis factor-α levels were decreased by gintonin, along with a reduction in pain-related behaviors. In addition, the fecal microbiota from gintonin-treated mice had relatively more Lactobacillaceae and Lachnospiraceae and less Bacteroidaceae than microbiota from the control mice. Moreover, gintonin inhibited transient receptor potential vanilloid (TRPV) 1 and TRPV4 associated with visceral hypersensitivity and voltage-gated Na⁺ 1.5 channels associated with GI function. These results suggest that gintonin may be one of the effective components in the treatment of IBS. Full article

(This article belongs to the Special Issue Transient Receptor Potential (TRP) Channels as Novel Therapeutic Targets)

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17 pages, 3170 KiB

Open AccessArticle

Photodynamic Therapy as a Novel Therapeutic Modality Applying Quinizarin-Loaded Nanocapsules and 3D Bioprinting Skin Permeation for Inflammation Treatment

by Stéphanie R. do Amaral, Camila F. Amantino, Aleksandar Atanasov, Stefanie Sousa, Richard Moakes, Sonia Maria Oliani, Liam M. Grover and Fernando L. Primo

Pharmaceuticals 2024, 17(9), 1169; https://doi.org/10.3390/ph17091169 - 4 Sep 2024

Abstract

Skin inflammation associated with chronic diseases involves a direct role of keratinocytes in its immunopathogenesis, triggering a cascade of immune responses. Despite this, highly targeted treatments remain elusive, highlighting the need for more specific therapeutic strategies. In this study, nanocapsules containing quinizarin (QZ/NC) [...] Read more.

Skin inflammation associated with chronic diseases involves a direct role of keratinocytes in its immunopathogenesis, triggering a cascade of immune responses. Despite this, highly targeted treatments remain elusive, highlighting the need for more specific therapeutic strategies. In this study, nanocapsules containing quinizarin (QZ/NC) were developed and evaluated in an in vitro model of keratinocyte-mediated inflammation, incorporating the action of photodynamic therapy (PDT) and analyzing permeation in a 3D skin model. Comprehensive physicochemical, stability, cytotoxicity, and permeation analyses of the nanomaterials were conducted. The nanocapsules demonstrated desirable physicochemical properties, remained stable throughout the analysis period, and exhibited no spectroscopic alterations. Cytotoxicity tests revealed no toxicity at the lowest concentrations of QZ/NC. Permeation and cellular uptake studies confirmed QZ/NC permeation in 3D skin models, along with intracellular incorporation and internalization of the drug, thereby enhancing its efficacy in drug delivery. The developed model for inducing the inflammatory process in vitro yielded promising results, particularly when the synthesized nanomaterial was combined with PDT, showing a reduction in cytokine levels. These findings suggest a potential new therapeutic approach for treating inflammatory skin diseases. Full article

(This article belongs to the Special Issue Photosensitizers and Drug Delivery Systems for Photodynamic Therapy)

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14 pages, 1903 KiB

Open AccessArticle

Characterization and Evaluation of the Cytotoxicity of Pregabalin Gels for Oral Application

by Gabriela Monteiro Barbosa Xavier, Lindalva Maria de Meneses Costa Ferreira, Marcele Fonseca Passos, Ana Paula Drummond Rodrigues, Felipe Tuji de Castro Franco, Cecy Martins Silva, José Otávio Carréra Silva Júnior, Roseane Maria Ribeiro-Costa and Jesuína Lamartine Nogueira Araújo

Pharmaceuticals 2024, 17(9), 1168; https://doi.org/10.3390/ph17091168 - 4 Sep 2024

Abstract

The efficacy of pregabalin in pain treatment has led to the search for new formulations for its use through different routes of administration. This study aimed to prepare, characterize, and evaluate the cytotoxicity of pregabalin (PG) gels for topical application in the oral [...] Read more.

The efficacy of pregabalin in pain treatment has led to the search for new formulations for its use through different routes of administration. This study aimed to prepare, characterize, and evaluate the cytotoxicity of pregabalin (PG) gels for topical application in the oral cavity. Solutions with three different concentrations of PG were prepared and added to a 1.0% carbopol gel base. Thermal analyses (TG and DSC) and FTIR were performed on the gel and pure pregabalin. Stability (preliminary and accelerated) and rheology studies were also conducted on the gels. Cytotoxicity was evaluated in human gingival fibroblasts in the following groups: WG (1.0% carbopol gel base), PG2G (2.0% pregabalin gel), PG5G (5.0% pregabalin gel), and PG10G (10% pregabalin gel). A transparent and homogeneous gel with a pH of 6 was obtained. The formulations showed stability, and the different drug concentrations did not influence the product’s characteristics. None of the tested groups showed cytotoxicity for the analyzed cells. The pregabalin gels exhibited favorable and non-toxic characteristics for human gingival fibroblasts in vitro. Therefore, this product may be a promising therapeutic alternative for topical application in the oral mucosa. Full article

(This article belongs to the Topic Research in Pharmacological Therapies)

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17 pages, 2672 KiB

Open AccessArticle

Mannitol-Coated Hydroxypropyl Methylcellulose as a Directly Compressible Controlled Release Excipient for Moisture-Sensitive Drugs: A Stability Perspective

by Christina Yong Xin Kang, Keat Theng Chow, Yuan Siang Lui, Antoine Salome, Baptiste Boit, Philippe Lefevre, Tze Ning Hiew, Rajeev Gokhale and Paul Wan Sia Heng

Pharmaceuticals 2024, 17(9), 1167; https://doi.org/10.3390/ph17091167 - 4 Sep 2024

Abstract

Background/Objectives: Hydroxypropyl methylcellulose (HPMC) is one of the most commonly used hydrophilic polymers in formulations of matrix tablets for controlled release applications. However, HPMC attracts moisture and poses issues with drug stability in formulations containing moisture-sensitive drugs. Methods: Herein, the moisture sorption behavior [...] Read more.

Background/Objectives: Hydroxypropyl methylcellulose (HPMC) is one of the most commonly used hydrophilic polymers in formulations of matrix tablets for controlled release applications. However, HPMC attracts moisture and poses issues with drug stability in formulations containing moisture-sensitive drugs. Methods: Herein, the moisture sorption behavior of excipients and drug stability using aspirin as the model drug in matrix tablets were evaluated, using HPMC and the newly developed mannitol-coated HPMC, under accelerated stability conditions (40 °C, 75% relative humidity) with open and closed dishes. Results: Tablets prepared with mannitol-coated HPMC showed a slower drug degradation rate compared to tablets prepared with directly compressible HPMC. Initial moisture content and hygroscopicity were stronger predictors of drug stability compared to water activity when comparing samples without similar moisture content. In the early stage (day 0 to 30), the aspirin degradation rate was similar in both open and closed conditions, as moisture content is the main degradation contributor. In the later stage (day 30 to 90), aspirin degradation was faster under closed conditions than under open conditions, likely due to autocatalytic effects caused by the volatile acidic by-product entrapped in the closed environment. Conclusions: The findings from this study reinforced the importance of judicious excipient selection based on the understanding of excipient–moisture interactions to maximize the chemical stability of moisture-sensitive drugs. Mannitol-coated HPMC is a promising addition to the formulator’s toolbox for the formulation of controlled release dosage forms by direct compression. Full article

(This article belongs to the Special Issue Preparation Technologies and Dissolution Behaviour of Oral Solids)

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18 pages, 4129 KiB

Open AccessArticle

In Vitro Studies of Genistein Lipophilic Derivatives as Potential UV Radiation Protectors

by Magdalena Skonieczna, Kinga Plasa, Ewa Borowska, Agata Jakubowska, Wiesław Szeja and Anna Kasprzycka

Pharmaceuticals 2024, 17(9), 1166; https://doi.org/10.3390/ph17091166 - 3 Sep 2024

Abstract

The major environmental factor responsible for skin cancer is ultraviolet (UV) radiation, present in sunlight. UV radiation is directly linked to the production of reactive oxygen species (ROS), which accumulate in exposed cells and cause serious damage. The antioxidant systems present in cells [...] Read more.

The major environmental factor responsible for skin cancer is ultraviolet (UV) radiation, present in sunlight. UV radiation is directly linked to the production of reactive oxygen species (ROS), which accumulate in exposed cells and cause serious damage. The antioxidant systems present in cells cannot always sufficiently neutralize the ROS. Therefore, supplementation with exogenous antioxidants has been proposed. The antioxidant properties of some isoflavones, such as genistein, have already been well-proven. Genistein has limited bioavailability. However, its derivatives, with increased lipophilicity, could facilitate its transfer into cells, where they can expose its antioxidative potential. This study aims to investigate three genistein derivatives, with greater lipophilicity than the native compound, regarding their cytotoxicity, antioxidative properties, and effect on the cell cycle in normal human dermal fibroblasts (NHDF) and a melanoma cancer cell line (Me45). Results showed that lipophilic modification of the genistein molecule changes the biological response of NHDF and Me45 cell lines to UV-C radiation, but the lipophilicity cannot be directly linked with the activity of the compounds. A comparison of the effects of the genistein derivatives on healthy and cancerous cells suggests that their mode of action strongly depends on the type of cell involved. Full article

(This article belongs to the Special Issue Targeting Apoptosis as a Strategy for Developing New Drugs)

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15 pages, 1581 KiB

Open AccessSystematic Review

Use of Ketamine in Patients with Multifactorial Neuropathic Pain: A Systematic Review and Meta-Analysis

by Alejandro Bruna-Mejias, Vicente Baeza, Javiera Gamboa, Belen Baez Flores, Jessica San Martin, Constanza Astorga, Javiera Leyton, Pablo Nova-Baeza, Mathias Orellana-Donoso, Alejandra Suazo-Santibañez, Alvaro Becerra-Farfán, Gustavo Oyanedel-Amaro and Juan Jose Valenzuela-Fuenzalida

Pharmaceuticals 2024, 17(9), 1165; https://doi.org/10.3390/ph17091165 - 3 Sep 2024

Abstract

Neuropathic pain (NP) is a heterogeneous group of conditions characterized by the experience of a number of sensory disturbances including pain, burning sensations, paroxysms of stabbing pain, dysesthesias, allodynia, and hyperalgesia. The above-mentioned sensations may occur in a specific dermatome area or other [...] Read more.

Neuropathic pain (NP) is a heterogeneous group of conditions characterized by the experience of a number of sensory disturbances including pain, burning sensations, paroxysms of stabbing pain, dysesthesias, allodynia, and hyperalgesia. The above-mentioned sensations may occur in a specific dermatome area or other delimited region of the body. The objective of this review was to analyze the evidence for ketamine in multifactorial neuropathic pain. The research group systematically searched the databases MEDLINE (via PubMed), EMBASE, SCOPUS, the Cochrane Central Register of Controlled Trials, the Cumulative Index to Nursing and Allied Health Literature (Cinahl), and the Web of Science. The findings of this review show that different forms of low doses of ketamine (LDK) do not present statistically significant changes for any of the scales included. In this study, the total symptom score [standardized mean difference (SMD) = −3.59, confidence interval (CI) = −4.16 to −3.02, and p < 0.00001], neuropathy impairment score (SMD = −1.42, CI = −3.68 to 0.84, and p = 0.22), and neuropathy symptom checklist (SMD = −0.09, CI = −0.15 to −0.02, and p = 0.01) were taken into account. For finality compared to the use of a placebo, the findings suggest that LDK does not exhibit significant differences in terms of pain reduction and functionality. Moreover, no specific dosages are identified to support the use of LDK in the reduction in NP. Full article

(This article belongs to the Section Pharmacology)

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25 pages, 1617 KiB

Open AccessReview

Photoantimicrobial and Photoantiviral Textiles: Underestimated Potential

by Alexander Efimov and Serge Mordon

Pharmaceuticals 2024, 17(9), 1164; https://doi.org/10.3390/ph17091164 - 3 Sep 2024

Abstract

In this review, we summarize the present state of a rapidly developing field of light-activated antimicrobial textiles and their underestimated potential and opportunities. Full article

(This article belongs to the Special Issue The 20th Anniversary of Pharmaceuticals—The application of Adjuvants and Nanomaterials in Antimicrobial Intervention)

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17 pages, 490 KiB

Open AccessReview

Drug Delivery Systems for Glaucoma: A Narrative Review

by Antonio M. Fea, Veronica Vallino, Michela Cossu, Valentina Marica, Cristina Novarese, Michele Reibaldi and Francesco Petrillo

Pharmaceuticals 2024, 17(9), 1163; https://doi.org/10.3390/ph17091163 - 2 Sep 2024

Abstract

Glaucoma is one of the world’s leading causes of blindness, and its management is challenging. The main objective is to lower intraocular pressure through medical, para-surgical, and surgical therapy. Medical therapy often represents the first line of treatment. Although effective in many cases, [...] Read more.

Glaucoma is one of the world’s leading causes of blindness, and its management is challenging. The main objective is to lower intraocular pressure through medical, para-surgical, and surgical therapy. Medical therapy often represents the first line of treatment. Although effective in many cases, the eye drops are accompanied by significant problems. They require high patient compliance and can be associated with various side effects, limiting their efficacy. Consequently, the research for new drug delivery systems trying to overcome these limitations is ongoing: numerous devices are developing and gradually entering clinical practice. These new therapeutic options may offer better control of the intraocular pressure, with fewer side effects, and are less dependent on patients’ compliance. Hence, the research in this field continues to flourish. This review summarizes the most recent findings in the scientific literature, underlines the role and possible limitations of the new glaucoma drug delivery systems in clinical practice, and recognizes their new horizons and perspectives. Full article

(This article belongs to the Special Issue 20th Anniversary of Pharmaceuticals—Advances in Pathophysiology, Pharmacology and Neuroprotection in Glaucoma)

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14 pages, 1910 KiB

Open AccessArticle

Development and Validation of a Simple UV–HPLC Method to Quantify the Memantine Drug Used in Alzheimer’s Treatment

by Débora Nunes, Tânia G. Tavares, Frenacisco Xavier Malcata, Joana A. Loureiro and Maria Carmo Pereira

Pharmaceuticals 2024, 17(9), 1162; https://doi.org/10.3390/ph17091162 - 2 Sep 2024

Abstract

Memantine, a non-competitive NMDA receptor antagonist, is used to treat Alzheimer’s disease. Therefore, loading memantine in nanoparticles (NPs) could be an essential tool to improve the treatment effectiveness while reducing drug toxicity. Even though some approaches have been described to quantify memantine, none [...] Read more.

Memantine, a non-competitive NMDA receptor antagonist, is used to treat Alzheimer’s disease. Therefore, loading memantine in nanoparticles (NPs) could be an essential tool to improve the treatment effectiveness while reducing drug toxicity. Even though some approaches have been described to quantify memantine, none reported optimized methods using high-performance liquid chromatography resorting to ultraviolet detection (UV–HPLC) to determine encapsulation in NPs. The present research developed a HPLC method using pre-column derivatization for quantitatively analyzing memantine hydrochloride in NPs. Memantine was derivatized using 9-fluorenylmethyl chloroformate (FMOC). The developed method was fully validated regarding suitability, specificity, linearity, sensitivity, precision, accuracy, and robustness according to the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use guidelines. The retention time of memantine was 11.393 ± 0.003 min, with a mean recovery of 92.9 ± 3.7%. The new chromatographic method was validated and found to respond linearly over 5–140 μg/mL, with a high coefficient of determination. Intraday precision lay between 3.6% and 4.6%, and interday precision between 4.2% and 9.3%. The stability of memantine was also tested at 4 °C and −20 °C, and no signs of decay were found for up to 6 months. The new method was properly validated and proved simple, sensitive, specific, accurate, and precise for determining memantine encapsulation efficiency in lipid NPs. Greenness was evaluated, presenting a final score of 0.45. In the future, this methodology could also be applied to quantify memantine in different nanoformulations. Full article

(This article belongs to the Special Issue Therapeutic Drug Monitoring and Adverse Drug Reactions)

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