Frontiers in Hydrogel-Based Drug Delivery Systems

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 (20 November 2023) | Viewed by 14719

Special Issue Editors


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Guest Editor
School of Pharmacy, Collage of Pharmacy, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
Interests: drug delivery systems; transdermal drug delivery; pharmaceutical dosage forms; microemulsion; liposome
Special Issues, Collections and Topics in MDPI journals

E-Mail Website
Guest Editor
School of Pharmacy, College of Pharmacy, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
Interests: nanomedicine; biomaterials; topical/transdermal delivery; photodynamic therapy; pharmaceutical engineering
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

This Special Issue on “Frontiers in Hydrogel-based Drug Delivery Systems” is based on recent developments, designs, characterizations, and applications of hydrogels. Hydrogels play a very important role in gene delivery, drug delivery, and tissue regeneration, etc. Due to good biocompatibility, biodegradability, and negligible toxicity, this versatile drug carrier system has attracted a number of multidisciplinary researchers, who want to utilize hydrogels as a controlled drug delivery system for the management of different disorders. Hence, multiple interlinked functions are executed by this drug carrier system.  

This Special Issue aims to highlight and overcome the challenges faced by the low-aqueous-soluble drugs while constructing versatile smart hydrogel drug-delivery systems. We invite articles based on novel hydrogel drug delivery systems that overcome the limitations concerned with drug administration and enhance the life quality of patients.

We look forward to receiving your contributions. 

Prof. Dr. Pao-Chu Wu
Dr. Yi-Ping Fang
Guest Editors

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Keywords

  • hydrogel
  • biomaterial
  • drug delivery
  • tissue engineering
  • controlled release
  • biomedical application

Published Papers (6 papers)

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Research

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17 pages, 4199 KiB  
Article
Injectable In-Situ Forming Depot Based on PLGA and PLGA-PEG-PLGA for Sustained-Release of Risperidone: In Vitro Evaluation and Pharmacokinetics in Rabbits
by Seyedeh Nesa Rezaeian Shiadeh, Farzin Hadizadeh, Elham Khodaverdi, Mahmoud Gorji Valokola, Saleh Rakhshani, Hossein Kamali and Ali Nokhodchi
Pharmaceutics 2023, 15(4), 1229; https://doi.org/10.3390/pharmaceutics15041229 - 13 Apr 2023
Cited by 3 | Viewed by 2103
Abstract
In the current research, novel drug delivery systems based on in situ forming gel (ISFG) (PLGA-PEG-PLGA) and in situ forming implant (ISFI) (PLGA) were developed for one-month risperidone delivery. In vitro release evaluation, pharmacokinetics, and histopathology studies of ISFI, ISFG, and Risperdal CONSTA [...] Read more.
In the current research, novel drug delivery systems based on in situ forming gel (ISFG) (PLGA-PEG-PLGA) and in situ forming implant (ISFI) (PLGA) were developed for one-month risperidone delivery. In vitro release evaluation, pharmacokinetics, and histopathology studies of ISFI, ISFG, and Risperdal CONSTA® were compared in rabbits. Formulation containing 50% (w/w %) of PLGA-PEG-PLGA triblock revealed sustained release for about one month. Scanning electron microscopy (SEM) showed a porous structure for ISFI, while a structure with fewer pores was observed in the triblock. Cell viability in ISFG formulation in the first days was more than ISFI due to the gradual release of NMP to the release medium. Pharmacokinetic data displayed that optimal PLGA-PEG-PLGA creates a consistent serum level in vitro and in vivo through 30 days, and histopathology results revealed nearly slight to moderate pathological signs in the rabbit’s organs. The shelf life of the accelerated stability test didn’t affect the results of the release rate test and demonstrated stability in 24 months. This research confirms the better potential of the ISFG system compared with ISFI and Risperdal CONSTA®, which would increase patients’ compliance and avoid problems of further oral therapy. Full article
(This article belongs to the Special Issue Frontiers in Hydrogel-Based Drug Delivery Systems)
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23 pages, 8298 KiB  
Article
Fabrication of Stimuli-Responsive Quince/Mucin Co-Poly (Methacrylate) Hydrogel Matrices for the Controlled Delivery of Acyclovir Sodium: Design, Characterization and Toxicity Evaluation
by Aysha Aslam, Muhammad Umer Ashraf, Kashif Barkat, Asif Mahmood, Muhammad Ajaz Hussain, Muhammad Farid-ul-Haq, Manar O. Lashkar and Heba A. Gad
Pharmaceutics 2023, 15(2), 650; https://doi.org/10.3390/pharmaceutics15020650 - 15 Feb 2023
Cited by 10 | Viewed by 2139
Abstract
Free-radical polymerization technique was adopted to fabricate a stimuli-responsive intelligent quince/mucin co-poly (methacrylate) hydrogel for the controlled delivery of acyclovir sodium. The developed hydrogel matrices were appraised using different parameters, such as drug loading (%), swelling kinetics, pH- and electrolyte-responsive swelling, and sol–gel [...] Read more.
Free-radical polymerization technique was adopted to fabricate a stimuli-responsive intelligent quince/mucin co-poly (methacrylate) hydrogel for the controlled delivery of acyclovir sodium. The developed hydrogel matrices were appraised using different parameters, such as drug loading (%), swelling kinetics, pH- and electrolyte-responsive swelling, and sol–gel fraction. Drug-excipient compatibility study, scanning electron microscopy, thermal analysis, powder X-ray diffraction (PXRD) analysis, in vitro drug release studies, drug release kinetics and acute oral toxicity studies were conducted. The results of drug loading revealed an acyclovir sodium loading of 63–75% in different formulations. The hydrogel discs exhibited pH-responsive swelling behavior, showing maximum swelling in a phosphate buffer with a pH of 7.4, but negligible swelling was obvious in an acidic buffer with a pH of 1.2. The swelling kinetics of the developed hydrogel discs exhibited second-order kinetics. Moreover, the hydrogel discs responded to the concentration of electrolytes (CaCl2 and NaCl). The results of the FTIR confirm the formation of the hydrogel via free-radical polymerization. However, the major peaks of acyclovir remain intact, proving drug-excipient compatibility. The results of the SEM analysis reveal the porous, rough surface of the hydrogel discs with multiple cracks and pores over the surface. The results of the PXRD disclose the amorphous nature of the fabricated hydrogel. The dissolution studies showed a minor amount of acyclovir sodium released in an acidic environment, while an extended release up to 36 h in the phosphate buffer was observed. The drug release followed Hixen–Crowell’s kinetics with Fickian diffusion mechanism. The toxicity studies demonstrated the non-toxic nature of the polymeric carrier system. Therefore, these results signify the quince/mucin co-poly (methacrylate) hydrogel as a smart material with the potential to deliver acyclovir into the intestine for an extended period of time. Full article
(This article belongs to the Special Issue Frontiers in Hydrogel-Based Drug Delivery Systems)
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23 pages, 3578 KiB  
Article
Self-Assembling Injectable Hydrogel for Controlled Drug Delivery of Antimuscular Atrophy Drug Tilorone
by Mohamed M. Abdelghafour, Ágota Deák, Tamás Kiss, Mária Budai-Szűcs, Gábor Katona, Rita Ambrus, Bálint Lőrinczi, Anikó Keller-Pintér, István Szatmári, Diána Szabó, László Rovó and László Janovák
Pharmaceutics 2022, 14(12), 2723; https://doi.org/10.3390/pharmaceutics14122723 - 6 Dec 2022
Cited by 2 | Viewed by 2636
Abstract
A two-component injectable hydrogel was suitably prepared for the encapsulation and prolonged release of tilorone which is an antimuscular atrophy drug. The rapid (7–45 s, depending on the polymer concentration) in situ solidifications of the hydrogel were evoked by the evolving Schiff-base bonds [...] Read more.
A two-component injectable hydrogel was suitably prepared for the encapsulation and prolonged release of tilorone which is an antimuscular atrophy drug. The rapid (7–45 s, depending on the polymer concentration) in situ solidifications of the hydrogel were evoked by the evolving Schiff-base bonds between the aldehyde groups of modified PVA (4-formyl benzoate PVA, PVA-CHO, 5.9 mol% functionalization degree) and the amino groups of 3-mercaptopropionate chitosan (CHIT-SH). The successful modification of the initial polymers was confirmed by both FTIR and NMR measurements; moreover, a new peak appeared in the FTIR spectrum of the 10% w/v PVA-CHO/CHIT-SH hydrogel at 1647 cm−1, indicating the formation of a Schiff base (–CH=N–) and confirming the interaction between the NH2 groups of CHIT–SH and the CHO groups of PVA-CHO for the formation of the dynamic hydrogel. The reaction between the NH2 and CHO groups of the modified biopolymers resulted in a significant increase in the hydrogel’s viscosity which was more than one thousand times greater (9800 mPa·s) than that of the used polymer solutions, which have a viscosity of only 4.6 and 5.8 mPa·s, respectively. Furthermore, the initial chitosan was modified with mercaptopropionic acid (thiol content = 201.85 ± 12 µmol/g) to increase the mucoadhesive properties of the hydrogel. The thiolated chitosan showed a significant increase (~600 mN/mm) in adhesion to the pig intestinal membrane compared to the initial one (~300 mN/mm). The in vitro release of tilorone from the hydrogel was controlled with the crosslinking density/concentration of the hydrogel; the 10% w/v PVA-CHO/CHIT-SH hydrogel had the slowest releasing (21.7 h−1/2) rate, while the 2% w/v PVA-CHO/CHIT-SH hydrogel had the fastest releasing rate (34.6 h−1/2). Due to the characteristics of these hydrogels, their future uses include tissue regeneration scaffolds, wound dressings for skin injuries, and injectable or in situ forming drug delivery systems. Eventually, we hope that the developed hydrogel will be useful in the local treatment of muscle atrophy, such as laryngotracheal atrophy. Full article
(This article belongs to the Special Issue Frontiers in Hydrogel-Based Drug Delivery Systems)
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21 pages, 3481 KiB  
Article
Preparation of pH-Responsive Hydrogels Based on Chondroitin Sulfate/Alginate for Oral Drug Delivery
by Muhammad Suhail, Hamid Ullah, Quoc Lam Vu, Arshad Khan, Ming-Jun Tsai and Pao-Chu Wu
Pharmaceutics 2022, 14(10), 2110; https://doi.org/10.3390/pharmaceutics14102110 - 2 Oct 2022
Cited by 11 | Viewed by 2580
Abstract
This study investigates pH-sensitive hydrogels based on biocompatible, biodegradable polysaccharides and natural polymers such as chondroitin sulfate and alginate in combination with synthetic monomer such as acrylic acid, as controlled drug carriers. Investigations were conducted for chondroitin sulfate/alginate-graft-poly(acrylic acid) hydrogel in [...] Read more.
This study investigates pH-sensitive hydrogels based on biocompatible, biodegradable polysaccharides and natural polymers such as chondroitin sulfate and alginate in combination with synthetic monomer such as acrylic acid, as controlled drug carriers. Investigations were conducted for chondroitin sulfate/alginate-graft-poly(acrylic acid) hydrogel in various mixing ratios of chondroitin sulfate, alginate and acrylic acid in the presence of ammonium persulfate and N′,N′-Methylene bisacrylamide. Crosslinking and loading of drug were confirmed by Fourier transform infrared spectroscopy. Thermal stability of both polymers was enhanced after crosslinking as indicated by thermogravimetric analysis and differential scanning calorimeter thermogram of developed hydrogel. Similarly, surface morphology was evaluated by scanning electron microscopy, whereas crystallinity of the polymers and developed hydrogel was investigated by powder X-ray diffraction. Furthermore, swelling and drug-release studies were investigated in acidic and basic medium of pH 1.2 and 7.4 at 37 °C, respectively. Maximum swelling and drug release were detected at pH 7.4 as compared to pH 1.2. Increased incorporation of hydrogel contents led to an increase in porosity, drug loading, and gel fraction while a reduction in sol fraction was seen. The polymer volume fraction was found to be low at pH 7.4 compared to pH 1.2, indicating a prominent and greater swelling of the prepared hydrogels at pH 7.4. Likewise, a biodegradation study revealed a slow degradation rate of the developed hydrogel. Hence, we can conclude from the results that a fabricated system of hydrogel could be used as a suitable carrier for the controlled delivery of ketorolac tromethamine. Full article
(This article belongs to the Special Issue Frontiers in Hydrogel-Based Drug Delivery Systems)
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20 pages, 4380 KiB  
Article
Preparation, In Vitro Characterization, and Cytotoxicity Evaluation of Polymeric pH-Responsive Hydrogels for Controlled Drug Release
by Muhammad Suhail, Jia-Yu Liu, Ming-Chia Hung, I-Hui Chiu, Muhammad Usman Minhas and Pao-Chu Wu
Pharmaceutics 2022, 14(9), 1864; https://doi.org/10.3390/pharmaceutics14091864 - 3 Sep 2022
Cited by 9 | Viewed by 2150
Abstract
The aim of the current investigation was based on the development of pH-responsive hydrogels of chondroitin sulfate, carbopol, and polyvinyl alcohol polymerized with acrylic acid in the presence of ammonium persulfate and ethylene glycol dimethylacrylate for controlled drug delivery. A free radical polymerization [...] Read more.
The aim of the current investigation was based on the development of pH-responsive hydrogels of chondroitin sulfate, carbopol, and polyvinyl alcohol polymerized with acrylic acid in the presence of ammonium persulfate and ethylene glycol dimethylacrylate for controlled drug delivery. A free radical polymerization technique was used for the preparation of these pH-responsive hydrogels. The gel fraction of the prepared hydrogels was increased with the increase in the chondroitin sulfate, carbopol, polyvinyl alcohol, and acrylic acid content, while the sol-fraction was decreased. Swelling and drug release studies were performed in various pH conditions. Greater swelling and drug release were observed at high pH values (pH 4.6 and 7.4) as compared to low pH value (pH 1.2), representing the pH-responsive nature of the synthesized hydrogels. Porosity and drug loading were increased with the incorporation of high concentrations of hydrogel contents except polyvinyl alcohol, which showed reverse effects. Similarly, biodegradation study reported a slow degradation rate of the prepared hydrogels with the increase in hydrogel constituents. Cytotoxicity study proved the safe use of developed hydrogels as no toxic effect was shown on T84 human colon cancer cells. Similarly, various characterizations, including Fourier transform infrared spectroscopy, thermogravimetric analysis, differential scanning calorimetry, X-ray diffraction, and scanning electron microscopy, were performed for prepared hydrogels. Hence, we could demonstrate that the prepared hydrogels can be used as a promising drug carrier for the controlled delivery of drugs. Full article
(This article belongs to the Special Issue Frontiers in Hydrogel-Based Drug Delivery Systems)
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Review

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25 pages, 8684 KiB  
Review
Applications of Stimuli-Responsive Hydrogels in Bone and Cartilage Regeneration
by Xiaoqi Ni, Xin Xing, Yunfan Deng and Zhi Li
Pharmaceutics 2023, 15(3), 982; https://doi.org/10.3390/pharmaceutics15030982 - 18 Mar 2023
Cited by 11 | Viewed by 2335
Abstract
Bone and cartilage regeneration is an area of tremendous interest and need in health care. Tissue engineering is a potential strategy for repairing and regenerating bone and cartilage defects. Hydrogels are among the most attractive biomaterials in bone and cartilage tissue engineering, mainly [...] Read more.
Bone and cartilage regeneration is an area of tremendous interest and need in health care. Tissue engineering is a potential strategy for repairing and regenerating bone and cartilage defects. Hydrogels are among the most attractive biomaterials in bone and cartilage tissue engineering, mainly due to their moderate biocompatibility, hydrophilicity, and 3D network structure. Stimuli-responsive hydrogels have been a hot topic in recent decades. They can respond to external or internal stimulation and are used in the controlled delivery of drugs and tissue engineering. This review summarizes current progress in the use of stimuli-responsive hydrogels in bone and cartilage regeneration. The challenges, disadvantages, and future applications of stimuli-responsive hydrogels are briefly described. Full article
(This article belongs to the Special Issue Frontiers in Hydrogel-Based Drug Delivery Systems)
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