Advanced Bio-Hybrid Materials for Drug Delivery Systems - New Trends and Perspectives

A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Drug Delivery and Controlled Release".

Deadline for manuscript submissions: closed (15 July 2023) | Viewed by 33721

Special Issue Editors


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Institute of Organic Chemistry and Technology, Faculty of Chemical Engineering and Technology, Cracow University of Technology, 24 Warszawska St., 31-155 Cracow, Poland.
Interests: organic chemistry; medicinal chemistry; synthesis; pharmaceuticals; material characterization; polymers; nanomaterials; drug delivery systems; polymeric biomaterials; hydrogels; bio-hybrid hydrogels; advanced polymeric materials; polymeric biomaterials; biopolymers; drug delivery systems; natural and synthetic active substances; nanocarriers
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A. Chełkowski Institute of Physics and Silesian Center for Education and Interdisciplinary Research, University of Silesia in Katowice, 75 Pułku Piechoty 1, 41-500 Chorzów, Poland
Interests: anticancer activity; kinase inhibition; signalling cancer pathways; metal chelators; thiosemicarbazones; oxidative stress
Special Issues, Collections and Topics in MDPI journals

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Guest Editor
Faculty of Chemical Engineering and Technology, Institute of Organic Chemistry and Technology, Cracow University of Technology, 24 Warszawska St., 31155 Cracow, Poland
Interests: lipid nanocarriers; hydrogles; wound healing; skin disorders; skin regeneration; drug release kinetics; design of experiments (DOE); molecular dynamics (MD)
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Due to pollution of our environment, unhealthy lifestyle, as well as stress, causing a variety of chronic disorders, currently, both, the medical and pharmaceutical markets are developing at an intense rate. People need new solutions. Therefore, it is important to consider what the new trends are, as well as possible novel perspectives. There are so many questions related to this topic. This is why recently, many groups of scientists are focusing on the preparation and advanced functional bio-hybrid materials for biomedical applications and drug delivery systems. We can distinguish different systems based on polymeric, organic, inorganic micro/nanocarriers or their combination with biopolymeric, polymeric or hydrogel matrices, which enables the controlled, sustained or modified release of active substances derived from natural or synthetic origin. In addition to the synthesis, physicochemical and structural properties, it is very important to determine the drug release profile and ensure a safe therapeutic concentration. Moreover, from an application point of view, the cytotoxicity assays are essential. I believe that together we can make more, leading to a significant change in people’s quality of life.

This Special Issue will allow us to share achieved goals and new approaches in designing smart drug delivery systems.

Dr. Katarzyna Bialik-Wąs
Dr. Katarzyna Malarz
Dr. Małgorzata A. Miastkowska
Guest Editors

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Keywords

  • micro-/nanocarriers
  • advanced materials
  • bio-hybrid hydrogels
  • transdermal systems
  • controlled release
  • drug delivery systems
  • drug carriers
  • cytotoxicity assays
  • biodegradability
  • In vitro and 3D models

Published Papers (13 papers)

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Research

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20 pages, 3296 KiB  
Article
A Drug-Eluting Injectable NanoGel for Localized Delivery of Anticancer Drugs to Solid Tumors
by Brent Godau, Sadaf Samimi, Amir Seyfoori, Ehsan Samiei, Tahereh Khani, Parvaneh Naserzadeh, Alireza Hassani Najafabadi, Emal Lesha, Keivan Majidzadeh-A, Behnaz Ashtari, Gabriel Charest, Christophe Morin, David Fortin and Mohsen Akbari
Pharmaceutics 2023, 15(9), 2255; https://doi.org/10.3390/pharmaceutics15092255 - 31 Aug 2023
Cited by 2 | Viewed by 2256
Abstract
Systemically administered chemotherapy reduces the efficiency of the anticancer agent at the target tumor tissue and results in distributed drug to non-target organs, inducing negative side effects commonly associated with chemotherapy and necessitating repeated administration. Injectable hydrogels present themselves as a potential platform [...] Read more.
Systemically administered chemotherapy reduces the efficiency of the anticancer agent at the target tumor tissue and results in distributed drug to non-target organs, inducing negative side effects commonly associated with chemotherapy and necessitating repeated administration. Injectable hydrogels present themselves as a potential platform for non-invasive local delivery vehicles that can serve as a slow-releasing drug depot that fills tumor vasculature, tissue, or resection cavities. Herein, we have systematically formulated and tested an injectable shear-thinning hydrogel (STH) with a highly manipulable release profile for delivering doxorubicin, a common chemotherapeutic. By detailed characterization of the STH physical properties and degradation and release dynamics, we selected top candidates for testing in cancer models of increasing biomimicry. Two-dimensional cell culture, tumor-on-a-chip, and small animal models were used to demonstrate the high anticancer potential and reduced systemic toxicity of the STH that exhibits long-term (up to 80 days) doxorubicin release profiles for treatment of breast cancer and glioblastoma. The drug-loaded STH injected into tumor tissue was shown to increase overall survival in breast tumor- and glioblastoma-bearing animal models by 50% for 22 days and 25% for 52 days, respectively, showing high potential for localized, less frequent treatment of oncologic disease with reduced dosage requirements. Full article
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15 pages, 2665 KiB  
Article
Molecular Imaging Investigations of Polymer-Coated Cerium Oxide Nanoparticles as a Radioprotective Therapeutic Candidate
by Philip Reed McDonagh, Sundaresan Gobalakrishnan, Christopher Rabender, Vimalan Vijayaragavan and Jamal Zweit
Pharmaceutics 2023, 15(8), 2144; https://doi.org/10.3390/pharmaceutics15082144 - 15 Aug 2023
Cited by 2 | Viewed by 1060
Abstract
Cerium oxide nanoparticles (CONPs) have a unique surface redox chemistry that appears to selectively protect normal tissues from radiation induced damage. Our prior research exploring the biocompatibility of polymer-coated CONPs found further study of poly-acrylic acid (PAA)-coated CONPs was warranted due to improved [...] Read more.
Cerium oxide nanoparticles (CONPs) have a unique surface redox chemistry that appears to selectively protect normal tissues from radiation induced damage. Our prior research exploring the biocompatibility of polymer-coated CONPs found further study of poly-acrylic acid (PAA)-coated CONPs was warranted due to improved systemic biodistribution and rapid renal clearance. This work further explores PAA-CONPs’ radioprotective efficacy and mechanism of action related to tumor microenvironment pH. An ex vivo TUNEL assay was used to measure PAA-CONPs’ protection of the irradiated mouse colon in comparison to the established radioprotector amifostine. [18F]FDG PET imaging of spontaneous colon tumors was utilized to determine the effects of PAA-CONPs on tumor radiation response. In vivo MRI and an ex vivo clonogenic assay were used to determine pH effects on PAA-CONPs’ radioprotection in irradiated tumor-bearing mice. PAA-CONPs showed excellent radioprotective efficacy in the normal colon that was equivalent to uncoated CONPs and amifostine. [18F]FDG PET imaging showed PAA-CONPs do not affect tumor response to radiation. Normalization of tumor pH allowed some radioprotection of tumors by PAA-CONPs, which may explain their lack of tumor radioprotection in the acidic tumor microenvironment. Overall, PAA-CONPs meet the criteria for clinical application as a radioprotective therapeutic agent and are an excellent candidate for further study. Full article
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19 pages, 3704 KiB  
Article
Nanostructured Lipid Carrier Co-Loaded with Docetaxel and Magnetic Nanoparticles: Physicochemical Characterization and In Vitro Evaluation
by Auni Hamimi Idris, Che Azurahanim Che Abdullah, Nor Azah Yusof, Azren Aida Asmawi and Mohd Basyaruddin Abdul Rahman
Pharmaceutics 2023, 15(5), 1319; https://doi.org/10.3390/pharmaceutics15051319 - 22 Apr 2023
Cited by 2 | Viewed by 1778
Abstract
Lung cancer is currently the most prevalent cause of cancer mortality due to late diagnosis and lack of curative therapies. Docetaxel (Dtx) is clinically proven as effective, but poor aqueous solubility and non-selective cytotoxicity limit its therapeutic efficacy. In this work, a nanostructured [...] Read more.
Lung cancer is currently the most prevalent cause of cancer mortality due to late diagnosis and lack of curative therapies. Docetaxel (Dtx) is clinically proven as effective, but poor aqueous solubility and non-selective cytotoxicity limit its therapeutic efficacy. In this work, a nanostructured lipid carrier (NLC) loaded with iron oxide nanoparticles (IONP) and Dtx (Dtx-MNLC) was developed as a potential theranostic agent for lung cancer treatment. The amount of IONP and Dtx loaded into the Dtx-MNLC was quantified using Inductively Coupled Plasma Optical Emission Spectroscopy and high-performance liquid chromatography. Dtx-MNLC was then subjected to an assessment of physicochemical characteristics, in vitro drug release, and cytotoxicity. Dtx loading percentage was determined at 3.98% w/w, and 0.36 mg/mL IONP was loaded into the Dtx-MNLC. The formulation showed a biphasic drug release in a simulated cancer cell microenvironment, where 40% of Dtx was released for the first 6 h, and 80% cumulative release was achieved after 48 h. Dtx-MNLC exhibited higher cytotoxicity to A549 cells than MRC5 in a dose-dependent manner. Furthermore, the toxicity of Dtx-MNLC to MRC5 was lower than the commercial formulation. In conclusion, Dtx-MNLC shows the efficacy to inhibit lung cancer cell growth, yet it reduced toxicity on healthy lung cells and is potentially capable as a theranostic agent for lung cancer treatment. Full article
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16 pages, 3499 KiB  
Article
Poly(N-vinylcaprolactam)–Gold Nanorods–5 Fluorouracil Hydrogels: In the Quest of a Material for Topical Therapies against Melanoma Skin Cancer
by Mirian A. González-Ayón, Alondra Rochin-Galaviz, Arturo Zizumbo-López and Angel Licea-Claverie
Pharmaceutics 2023, 15(4), 1097; https://doi.org/10.3390/pharmaceutics15041097 - 29 Mar 2023
Cited by 2 | Viewed by 1572
Abstract
Chemically crosslinked hydrogels based on poly(N-vinylcaprolactam) (PNVCL) were synthetized by a photoinitiated chemical method. A galactose-based monomer, 2-lactobionamidoethyl methacrylate (LAMA), and N-vinylpyrrolidone (NVP) were added with the aim to improve the physical and chemical properties of hydrogels. The effects of [...] Read more.
Chemically crosslinked hydrogels based on poly(N-vinylcaprolactam) (PNVCL) were synthetized by a photoinitiated chemical method. A galactose-based monomer, 2-lactobionamidoethyl methacrylate (LAMA), and N-vinylpyrrolidone (NVP) were added with the aim to improve the physical and chemical properties of hydrogels. The effects of both comonomers on the swelling ratio (Q), volume phase transition temperature (VPTT), glass transition temperature (Tg), and Young’s moduli by mechanical compression below and above the VPTT were studied. Gold nanorods (GNRDs) and 5-fluorouracil (5FU) were embedded into the hydrogels, to study the drug release profiles with and without the excitation of GNRDs by irradiation in the near-infrared region (NIR). Results showed that the addition of LAMA and NVP increased the hydrogels’ hydrophilicity, elasticity, and VPTT. The loading of GNRDs in the hydrogels changed the release rate of 5FU when irradiated intermittently with an NIR laser. The present study reports on the preparation of a hydrogel-based platform of PNVCL-GNRDs−5FU as a potential hybrid anticancer hydrogel for chemo/photothermal therapy that could be applied against skin cancer for topical 5FU delivery. Full article
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20 pages, 6503 KiB  
Article
Montmorillonite–Rifampicin Nanohybrid for pH-Responsive Release of the Tuberculostatic
by Elmar Damasceno Junior, Raquel de Melo Barbosa, Rita de Cássia Dantas da Silva, Felipe dos Santos Costa, Djalma Ribeiro da Silva, César Viseras, Luana Perioli and Nedja Suely Fernandes
Pharmaceutics 2023, 15(2), 512; https://doi.org/10.3390/pharmaceutics15020512 - 3 Feb 2023
Cited by 2 | Viewed by 1393
Abstract
The present work describes the development of a hybrid and pH-responsive system for rifampicin using the clay mineral ‘montmorillonite’ as a nanocarrier. The influence of operational variables on the drug incorporation process was evaluated using 24 factorial designs. Under optimized conditions, the [...] Read more.
The present work describes the development of a hybrid and pH-responsive system for rifampicin using the clay mineral ‘montmorillonite’ as a nanocarrier. The influence of operational variables on the drug incorporation process was evaluated using 24 factorial designs. Under optimized conditions, the experiment allowed an incorporated drug dose equivalent to 98.60 ± 1.21 mg/g. Hybrid systems were characterized by different characterization techniques (FTIR, XRD, TGA, DSC, and SEM) to elucidate the mechanism of interaction between the compounds used. Through in vitro release studies, it was possible to verify the efficacy of the pH-dependent system obtained, with approximately 70% of the drug released after sixteen hours in simulated intestinal fluid. The adjustment of the experimental release data to the theoretical model of Higuchi and Korsmeyer–Peppas indicated that the release of rifampicin occurs in a prolonged form from montmorillonite. Elucidation of the interactions between the drug and this raw clay reinforces its viability as a novel carrier to develop an anti-TB/clay hybrid system with good physical and chemical stability. Full article
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17 pages, 4909 KiB  
Article
Design-of-Experiments (DoE)-Assisted Fabrication of Quercetin-Loaded Nanoemulgel and Its Evaluation against Human Skin Cancer Cell Lines
by Aman Chitkara, Bharti Mangla, Pankaj Kumar, Shamama Javed, Waquar Ahsan and Harvinder Popli
Pharmaceutics 2022, 14(11), 2517; https://doi.org/10.3390/pharmaceutics14112517 - 19 Nov 2022
Cited by 11 | Viewed by 1912
Abstract
Background: Quercetin (QCT) is a natural polyphenolic flavonoid showing great potential in the treatment of skin cancer. However, its use is limited owing to its poor water solubility, poor absorption, quick metabolism and excretion, as well as low stability. Preparation of nanoemulgel has [...] Read more.
Background: Quercetin (QCT) is a natural polyphenolic flavonoid showing great potential in the treatment of skin cancer. However, its use is limited owing to its poor water solubility, poor absorption, quick metabolism and excretion, as well as low stability. Preparation of nanoemulgel has been proven to be an effective approach to deliver the drugs topically due to various advantages associated with it. Objectives: This study aimed to prepare stable nanoemulgel of QCT using a Design-of-Experiments (DoE) tool for optimization, to characterize and to assess its in vivo toxicity and efficacy against human cancer cell lines in vitro. Methods: An ultrasonication emulsification method was used for the preparation of QCT-loaded nanoemulsion (QCT@NE). Box–Behnken design was used for the optimization of developed nanoemulgel. Then, in vitro characterization of prepared nanoemulsion was performed using Fourier Transform-Infra Red (FT-IR) spectroscopy, Scanning Electron Microscopy (SEM), particle size analysis, determination of zeta potential and entrapment efficiency (%EE). Further, the developed QCT-loaded nanoemulgel (QCT@NG) was characterized in vitro using texture profile analysis, viscosity and pH determination. Eventually, the cell cytotoxicity studies of the prepared nanoemulgel were performed on the skin cancer cell lines A431 followed by an acute toxicity and skin irritation study on male wistar rats in vivo. Results: The developed QCT@NE was found to be nanometric in size (173.1 ± 1.2 nm) with low polydispersity index (0.353 ± 0.13), zeta potential (−36.1 ± 5.9 mV), and showed good %EE (90.26%). The QCT@NG was found to be substantially more effective against the human skin carcinoma (A431) cell lines as compared to plain QCT with IC50 values of 108.5 and 579.0 µM, respectively. Skin irritation study showed no sign of toxicity and ensured safety for topical application. Hematological analysis revealed no significant differences between the treatment and control group in any biochemical parameter. In the nanoemulgel treatment group, there were no discernible differences in the liver enzymes, bilirubin, hemoglobin, total leukocyte and platelet counts as compared to the control group. Conclusions: The optimized QCT@NG was found to be an ideal and promising formulation for the treatment of skin cancer without showing skin irritation and organ toxicity. Full article
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22 pages, 7385 KiB  
Article
Bio-Hybrid Hydrogels Incorporated into a System of Salicylic Acid-pH/Thermosensitive Nanocarriers Intended for Cutaneous Wound-Healing Processes
by Katarzyna Bialik-Wąs, Małgorzata Miastkowska, Paulina Sapuła, Klaudia Pluta, Dagmara Malina, Jarosław Chwastowski and Mateusz Barczewski
Pharmaceutics 2022, 14(4), 773; https://doi.org/10.3390/pharmaceutics14040773 - 1 Apr 2022
Cited by 6 | Viewed by 2351
Abstract
In this paper, the preparation method of bio-hybrid hydrogels incorporated into a system of salicylic acid-pH/thermosensitive nanocarriers to speed up the wound-healing process was developed. This combination creates a dual drug delivery system, which releases the model hydrophobic active substance—salicylic acid—in a gradual [...] Read more.
In this paper, the preparation method of bio-hybrid hydrogels incorporated into a system of salicylic acid-pH/thermosensitive nanocarriers to speed up the wound-healing process was developed. This combination creates a dual drug delivery system, which releases the model hydrophobic active substance—salicylic acid—in a gradual and controlled manner for an extended time. Our research team has determined the various properties of bio-hybrid hydrogels based on their physicochemical (swelling degree, and degradation), structural (FT-IR), morphological (SEM), and mechanical (elongation tests) traits. Moreover, empty pH/thermosensitive nanocarriers and their salicylic acid-containing systems were characterized using the following methods: DLS, TG/DTG, and DSC. Additionally, salicylic acid release profiles directly from thermosensitive nanocarriers were compared to the bio-hybrid matrix. These studies were conducted in PBS (pH = 7.4) for 7 days using the USP4 method. To evaluate the antibacterial properties of the obtained materials, the inhibition of growth of Staphylococcus aureus, Escherichia coli, Candida albicans, and Aspergillus niger—as the main microorganisms responsible for human infections—were tested. The obtained results indicated that the pH/thermosensitive nanocarrier–salicylic acid system and bio-hybrid hydrogels are characterized by antibacterial activity against both S. aureus and E. coli. Full article
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21 pages, 1887 KiB  
Article
Polyphosphazene-Based Nanocarriers for the Release of Camptothecin and Epirubicin
by Javier Pérez Quiñones, Cornelia Roschger, Aitziber Iturmendi, Helena Henke, Andreas Zierer, Carlos Peniche-Covas and Oliver Brüggemann
Pharmaceutics 2022, 14(1), 169; https://doi.org/10.3390/pharmaceutics14010169 - 11 Jan 2022
Cited by 9 | Viewed by 1976
Abstract
The design and study of efficient polymer-based drug delivery systems for the controlled release of anticancer drugs is one of the pillars of nanomedicine. The fight against metastatic and invasive cancers demands therapeutic candidates with increased and selective toxicity towards malignant cells, long-term [...] Read more.
The design and study of efficient polymer-based drug delivery systems for the controlled release of anticancer drugs is one of the pillars of nanomedicine. The fight against metastatic and invasive cancers demands therapeutic candidates with increased and selective toxicity towards malignant cells, long-term activity and reduced side effects. In this sense, polyphosphazene nanocarriers were synthesized for the sustained release of the anticancer drugs camptothecin (CPT) and epirubicin (EPI). Linear poly(dichloro)phosphazene was modified with lipophilic tocopherol or testosterone glycinate, with antioxidant and antitumor activity, and with hydrophilic Jeffamine M1000 to obtain different polyphosphazene nanocarriers. It allowed us to encapsulate the lipophilic CPT and the more hydrophilic EPI. The encapsulation process was carried out via solvent exchange/precipitation, attaining a 9.2–13.6 wt% of CPT and 0.3–2.4 wt% of EPI. CPT-loaded polyphosphazenes formed 140–200 nm aggregates in simulated body physiological conditions (PBS, pH 7.4), resulting in an 80–100-fold increase of CPT solubility. EPI-loaded polyphosphazenes formed 250 nm aggregates in an aqueous medium. CPT and EPI release (PBS, pH 7.4, 37 °C) was monitored for 202 h, being almost linear during the first 8 h. The slow release of testosterone and tocopherol was also sustained for 150 h in PBS (pH 7.4 and 6.0) at 37 °C. The co-delivery of testosterone or tocopherol and the anticancer drugs from the nanocarriers was expected. Cells of the human breast cancer cell line MCF-7 demonstrated good uptake of anticancer-drug-loaded nanocarriers after 6 h. Similarly, MCF-7 spheroids showed good uptake of the anticancer-drug-loaded aggregates after 72 h. Almost all anticancer-drug-loaded polyphosphazenes exhibited similar or superior toxicity against MCF-7 cells and spheroids when compared to raw anticancer drugs. Additionally, cell-cycle arrest in the G2/M phase was increased in response to the drug-loaded nanocarriers. Almost no toxicity of anticancer-drug-loaded aggregates against primary human lung fibroblasts was observed. Furthermore, the aggregates displayed no hemolytic activity, which is in contrast to the parent anticancer drugs. Consequently, synthesized polyphosphazene-based nanocarriers might be potential nanomedicines for chemotherapy. Full article
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19 pages, 1989 KiB  
Article
Sustained Intra-Articular Release and Biocompatibility of Tacrolimus (FK506) Loaded Monospheres Composed of [PDLA-PEG1000]-b-[PLLA] Multi-Block Copolymers in Healthy Horse Joints
by Stefan M. Cokelaere, Wilhelmina M.G.A.C. Groen, Saskia G.M. Plomp, Janny C. de Grauw, Paul M. van Midwoud, Harrie H. Weinans, Chris H.A. van de Lest, Marianna A. Tryfonidou, P. René van Weeren and Nicoline M. Korthagen
Pharmaceutics 2021, 13(9), 1438; https://doi.org/10.3390/pharmaceutics13091438 - 10 Sep 2021
Cited by 1 | Viewed by 1934
Abstract
There is an increasing interest in controlled release systems for local therapy in the treatment of human and equine joint diseases, aiming for optimal intra-articular concentrations with no systemic side effects. In this study, the intra-articular tolerability and suitability for local and sustained [...] Read more.
There is an increasing interest in controlled release systems for local therapy in the treatment of human and equine joint diseases, aiming for optimal intra-articular concentrations with no systemic side effects. In this study, the intra-articular tolerability and suitability for local and sustained release of tacrolimus (FK506) from monospheres composed of [PDLA-PEG1000]-b-PLLA multiblock copolymers were investigated. Unloaded and tacrolimus-loaded (18.4 mg tacrolimus/joint) monospheres were injected into the joints of six healthy horses, with saline and hyaluronic acid (HA) in the contralateral joints as controls. Blood and synovial fluid were analysed for the tacrolimus concentration and biomarkers for inflammation and cartilage metabolism. After an initial burst release, sustained intra-articular tacrolimus concentrations (>20 ng/mL) were observed during the 42 days follow-up. Whole-blood tacrolimus levels were below the detectable level (<0.5 ng/mL). A transient inflammatory reaction was observed for all substances, evidenced by increases of the synovial fluid white blood cell count and total protein. Prostaglandin and glycosaminoglycan release were increased in joints injected with unloaded monospheres, which was mitigated by tacrolimus. Both tacrolimus-loaded monospheres and HA transiently increased the concentration of collagen II cleavage products (C2C). A histologic evaluation of the joints at the endpoint showed no pathological changes in any of the conditions. Together, these results indicate the good biocompatibility of intra-articular applied tacrolimus-loaded monospheres combined with prolonged local drug release while minimising the risk of systemic side effects. Further evaluation in a clinical setting is needed to determine if tacrolimus-loaded monospheres can be beneficial in the treatment of inflammatory joint diseases in humans and animals. Full article
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Review

Jump to: Research

43 pages, 9037 KiB  
Review
Controlled Drug Release from Nanoengineered Polysaccharides
by Ilker S. Bayer
Pharmaceutics 2023, 15(5), 1364; https://doi.org/10.3390/pharmaceutics15051364 - 28 Apr 2023
Cited by 14 | Viewed by 2486
Abstract
Polysaccharides are naturally occurring complex molecules with exceptional physicochemical properties and bioactivities. They originate from plant, animal, and microbial-based resources and processes and can be chemically modified. The biocompatibility and biodegradability of polysaccharides enable their increased use in nanoscale synthesis and engineering for [...] Read more.
Polysaccharides are naturally occurring complex molecules with exceptional physicochemical properties and bioactivities. They originate from plant, animal, and microbial-based resources and processes and can be chemically modified. The biocompatibility and biodegradability of polysaccharides enable their increased use in nanoscale synthesis and engineering for drug encapsulation and release. This review focuses on sustained drug release studies from nanoscale polysaccharides in the fields of nanotechnology and biomedical sciences. Particular emphasis is placed on drug release kinetics and relevant mathematical models. An effective release model can be used to envision the behavior of specific nanoscale polysaccharide matrices and reduce impending experimental trial and error, saving time and resources. A robust model can also assist in translating from in vitro to in vivo experiments. The main aim of this review is to demonstrate that any study that establishes sustained release from nanoscale polysaccharide matrices should be accompanied by a detailed analysis of drug release kinetics by modeling since sustained release from polysaccharides not only involves diffusion and degradation but also surface erosion, complicated swelling dynamics, crosslinking, and drug-polymer interactions. As such, in the first part, we discuss the classification and role of polysaccharides in various applications and later elaborate on the specific pharmaceutical processes of polysaccharides in ionic gelling, stabilization, cross-linking, grafting, and encapsulation of drugs. We also document several drug release models applied to nanoscale hydrogels, nanofibers, and nanoparticles of polysaccharides and conclude that, at times, more than one model can accurately describe the sustained release profiles, indicating the existence of release mechanisms running in parallel. Finally, we conclude with the future opportunities and advanced applications of nanoengineered polysaccharides and their theranostic aptitudes for future clinical applications. Full article
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41 pages, 9114 KiB  
Review
Alginate-Based Materials Loaded with Nanoparticles in Wound Healing
by Anna Froelich, Emilia Jakubowska, Monika Wojtyłko, Barbara Jadach, Michał Gackowski, Piotr Gadziński, Olga Napierała, Yulia Ravliv and Tomasz Osmałek
Pharmaceutics 2023, 15(4), 1142; https://doi.org/10.3390/pharmaceutics15041142 - 4 Apr 2023
Cited by 12 | Viewed by 6258
Abstract
Alginate is a naturally derived polysaccharide widely applied in drug delivery, as well as regenerative medicine, tissue engineering and wound care. Due to its excellent biocompatibility, low toxicity, and the ability to absorb a high amount of exudate, it is widely used in [...] Read more.
Alginate is a naturally derived polysaccharide widely applied in drug delivery, as well as regenerative medicine, tissue engineering and wound care. Due to its excellent biocompatibility, low toxicity, and the ability to absorb a high amount of exudate, it is widely used in modern wound dressings. Numerous studies indicate that alginate applied in wound care can be enhanced with the incorporation of nanoparticles, revealing additional properties beneficial in the healing process. Among the most extensively explored materials, composite dressings with alginate loaded with antimicrobial inorganic nanoparticles can be mentioned. However, other types of nanoparticles with antibiotics, growth factors, and other active ingredients are also investigated. This review article focuses on the most recent findings regarding novel alginate-based materials loaded with nanoparticles and their applicability as wound dressings, with special attention paid to the materials of potential use in the treatment of chronic wounds. Full article
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35 pages, 4795 KiB  
Review
Are Natural Compounds a Promising Alternative to Synthetic Cross-Linking Agents in the Preparation of Hydrogels?
by Paulina Sapuła, Katarzyna Bialik-Wąs and Katarzyna Malarz
Pharmaceutics 2023, 15(1), 253; https://doi.org/10.3390/pharmaceutics15010253 - 11 Jan 2023
Cited by 17 | Viewed by 3685
Abstract
The main aim of this review is to assess the potential use of natural cross-linking agents, such as genipin, citric acid, tannic acid, epigallocatechin gallate, and vanillin in preparing chemically cross-linked hydrogels for the biomedical, pharmaceutical, and cosmetic industries. Chemical cross-linking is one [...] Read more.
The main aim of this review is to assess the potential use of natural cross-linking agents, such as genipin, citric acid, tannic acid, epigallocatechin gallate, and vanillin in preparing chemically cross-linked hydrogels for the biomedical, pharmaceutical, and cosmetic industries. Chemical cross-linking is one of the most important methods that is commonly used to form mechanically strong hydrogels based on biopolymers, such as alginates, chitosan, hyaluronic acid, collagen, gelatin, and fibroin. Moreover, the properties of natural cross-linking agents and their advantages and disadvantages are compared relative to their commonly known synthetic cross-linking counterparts. Nowadays, advanced technologies can facilitate the acquisition of high-purity biomaterials from unreacted components with no additional purification steps. However, while planning and designing a chemical process, energy and water consumption should be limited in order to reduce the risks associated with global warming. However, many synthetic cross-linking agents, such as N,N′-methylenebisacrylamide, ethylene glycol dimethacrylate, poly (ethylene glycol) diacrylates, epichlorohydrin, and glutaraldehyde, are harmful to both humans and the environment. One solution to this problem could be the use of bio-cross-linking agents obtained from natural resources, which would eliminate their toxic effects and ensure the safety for humans and the environment. Full article
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15 pages, 1510 KiB  
Review
Advances in Injectable In Situ-Forming Hydrogels for Intratumoral Treatment
by Gi Ru Shin, Hee Eun Kim, Jae Ho Kim, Sangdun Choi and Moon Suk Kim
Pharmaceutics 2021, 13(11), 1953; https://doi.org/10.3390/pharmaceutics13111953 - 18 Nov 2021
Cited by 20 | Viewed by 3653
Abstract
Chemotherapy has been linked to a variety of severe side effects, and the bioavailability of current chemotherapeutic agents is generally low, which decreases their effectiveness. Therefore, there is an ongoing effort to develop drug delivery systems to increase the bioavailability of these agents [...] Read more.
Chemotherapy has been linked to a variety of severe side effects, and the bioavailability of current chemotherapeutic agents is generally low, which decreases their effectiveness. Therefore, there is an ongoing effort to develop drug delivery systems to increase the bioavailability of these agents and minimize their side effects. Among these, intratumoral injections using in situ-forming hydrogels can improve drugs’ bioavailability and minimize drugs’ accumulation in non-target organs or tissues. This review describes different types of injectable in situ-forming hydrogels and their intratumoral injection for cancer treatment, after which we discuss the antitumor effects of intratumoral injection of drug-loaded hydrogels. This review concludes with perspectives on the future applicability of, and challenges for, the adoption of this drug delivery technology. Full article
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