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Pharmaceuticals
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Progress of Hydrogel Applications in Novel Drug Delivery Platforms
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Progress of Hydrogel Applications in Novel Drug Delivery Platforms

A special issue of Pharmaceuticals (ISSN 1424-8247). This special issue belongs to the section "Pharmaceutical Technology".

Deadline for manuscript submissions: 25 August 2025 | Viewed by 4697

Special Issue Editors

Dr. Anna Drabczyk

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Guest Editor
Department of Organic Chemistry and Technology, Faculty of Chemical Engineering and Technology, Cracow University of Technology, Warszawska 24 Street, 31-155 Cracow, Poland
Interests: organic chemistry; medicinal chemistry; synthesis; pharmaceuticals; material characterization; polymers; nanomaterials
Dr. Katarzyna Bialik-Wąs

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Guest Editor
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; biopolymers; natural and synthetic active substances; nanocarriers
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Welcome to this Special Issue dedicated to “Progress of Hydrogel Applications in Novel Drug Delivery Platforms”. This Special Issue aims to provide a comprehensive overview of the latest developments and trends in the field of hydrogel-based drug delivery systems, offering valuable insights to both researchers and practitioners in the field of pharmaceutical and biomedical sciences. Hydrogels, due to their unique properties and versatile application, have gained significant attention in the field of drug delivery. Thanks to aspects like high water content, adaptive physicochemical characteristics, and biocompatibility, hydrogels have become ideal candidates for delivering a wide range of therapeutics. The ability to control drug release kinetics is one of the key advantages of hydrogel in terms of drug delivery. Hydrogels can achieve sustained and controlled release of active substances over extended periods of time by modulating the polymer composition and crosslinking density. Moreover, thanks to the sensitivity of hydrogels to various types of stimuli, such as changes in pH, temperature, or enzymatic activity, it is possible to adjust the release of drugs in the desired place. This is an extremely valuable feature when therapy requires strict drug administration or precision in dosage schedules. Thanks to the use of hydrogels, it is possible to target drug delivery by incorporating ligands such as peptides or antibodies placed in the hydrogel matrix, so they can be delivered directly to damaged tissues or cells, increasing therapeutic effectiveness while minimizing the effects of the drug on other areas. Hydrogels also play a key role in delivering not only synthetic chemicals but also biological substances such as proteins, peptides, and nucleic acids. Their moist environment helps maintain the stability and activity of delicate biomolecules, facilitating their controlled release and improving bioavailability. Additionally, hydrogel-based gene delivery systems have potential in gene therapy, enabling efficient and targeted delivery of therapeutic genes to treat genetic disorders and other diseases. In this Special Issue, we invite authors to publish their original research articles, reviews, and perspectives on the broadly understood use of hydrogels in the delivery of active substances and drugs. It is expected that introducing innovations in the engineering and use of hydrogels and popularizing research on new drug delivery systems will contribute to the invention of innovative therapeutic solutions. The purpose of this Special Issue is to bring together cutting-edge research and insights from leading experts in this field. We hope that the works published in the Special Issue will contribute to the exchange of knowledge and the establishment of research cooperation, thus contributing to the development of the field of hydrogel science.

Dr. Anna Drabczyk
Dr. Katarzyna Bialik-Wąs
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Pharmaceuticals is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • hydrogels
  • targeted drug delivery
  • drug release
  • drug delivery
  • smart hydrogels
  • stimuli-responsive hydrogels
  • controlled release
  • hydrogel-based drug delivery
  • drug carriers

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Published Papers (4 papers)

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Research

29 pages, 9610 KiB  
Article
Development and Evaluation of Hydrogel-Based Sulfasalazine-Loaded Nanosponges for Enhanced Topical Psoriasis Therapy
by Sunil Kumar, Anroop B. Nair, Varsha Kadian, Pooja Dalal, Babu Lal Jangir, Bandar Aldhubiab, Rashed M. Almuqbil, Ahmed S. Alnaim, Nouf Alwadei and Rekha Rao
Pharmaceuticals 2025, 18(3), 391; https://doi.org/10.3390/ph18030391 - 10 Mar 2025
Viewed by 470
Abstract
Background: The low solubility and poor skin permeability of sulfasalazine (SLZ) present significant challenges for its effective topical delivery. The objective of the current investigation is to formulate a hydrogel-based SLZ-loaded cyclodextrin nanosponge for topical therapy in psoriasis. Methods: SLZ-loaded nanosponges were prepared [...] Read more.
Background: The low solubility and poor skin permeability of sulfasalazine (SLZ) present significant challenges for its effective topical delivery. The objective of the current investigation is to formulate a hydrogel-based SLZ-loaded cyclodextrin nanosponge for topical therapy in psoriasis. Methods: SLZ-loaded nanosponges were prepared by the melt polymerization method and evaluated for physiochemical characteristics, drug release, and cytocompatibility. The selected nanosponges (SLZ-NS4) were transformed to hydrogel and further evaluated for rheology, texture, safety, skin permeability, and in vivo for anti-psoriatic effect in mouse tail and imiquimod-induced psoriasis-like inflammation models in mice. Results: Physiochemical data confirms nanoscale architecture, drug inclusion in nanosponges, crystalline structure, and formulation stability. The release profile of SLZ-NS4 revealed sustained release behavior (22.98 ± 2.24% in 3 h). Cytotoxicity assays indicated negligible toxicity against THP1 cells, resulting in higher viability of cells than pure SLZ (p < 0.05). The HET-CAM assay confirmed the safety, while confocal laser scanning microscopy demonstrated deeper skin permeation of SLZ. In the mouse tail model, a remarkable decline in relative epidermal thickness, potential improvement in percent orthokeratosis, and drug activity with respect to control was observed in animals treated with SLZ-NS4 hydrogel. The efficiency of the developed SLZ-NS4-loaded hydrogel in treating psoriasis was confirmed by the decline in PASI score (81.68 ± 3.61 and 84.86 ± 5.74 with 1 and 2% w/v of SLZ-NS-HG). Histopathological analysis and assessment of oxidative stress markers revealed the profound anti-psoriatic potential of the fabricated SLZ-NS4 hydrogel. Conclusions: These findings highlight the profound potential of the developed delivery system as an effective topical therapy for psoriasis. Full article
(This article belongs to the Special Issue Progress of Hydrogel Applications in Novel Drug Delivery Platforms)
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30 pages, 13089 KiB  
Article
Polylactic-Co-Glycolic Acid/Alginate/Neem Oil-Reduced Graphene Oxide as a pH-Sensitive Nanocarrier for Hesperidin Drug Delivery: Antimicrobial and Acute Otitis Media Assessments
by Saeed Abdul Kareem Saeed Al-Zuhairy, Sammar Fathy Elhabal, Mohamed Fathi Mohamed Elrefai, Sandra Hababeh, Jakline Nelson, Marwa Fady, Nahla A. Elzohairy, Tassneim M. Ewedah, Ibrahim S. Mousa and Ahmed Mohsen Elsaid Hamdan
Pharmaceuticals 2025, 18(3), 381; https://doi.org/10.3390/ph18030381 - 7 Mar 2025
Viewed by 451
Abstract
Background/Objectives: Hesperidin (HSP) is a potent phytochemical antioxidant and anti-inflammatory agent that protects against otitis media. However, due to its low solubility and bioavailability, a suitable delivery method is needed to overcome these problems. A hydrogel is a promising nanocarrier for controlled [...] Read more.
Background/Objectives: Hesperidin (HSP) is a potent phytochemical antioxidant and anti-inflammatory agent that protects against otitis media. However, due to its low solubility and bioavailability, a suitable delivery method is needed to overcome these problems. A hydrogel is a promising nanocarrier for controlled drug delivery in response to external stimuli, such as pH variations. Methods: Graphene oxide (GO)-based nanocarriers that encapsulate hesperidin (HSP) were further coated with a polylactic-co-glycolic acid/alginate (PLGA-Alg) hydrogel before being integrated into a green neem oil (N.O.) double emulsion to produce a synergistic effect and then characterized by different assays. Results: The nanocarriers exhibited a substantial particle size (168 ± 0.32 nm), with high encapsulation (89.86 ± 0.23%) and a zeta potential of 37 ± 0.43 mV. In vitro release studies conducted over 96 h indicated a sustained HSP release of 82% at pH 5.4 and 65% at pH 7.4. The GO-HSP-loaded neem oil double emulsion formulation exhibits substantial antibacterial activity, as evidenced by inhibition zones of 39 ± 0.02 mm against Staphylococcus epidermidis, and considerable antifungal activity against Candida albicans, with an inhibition zone of 43 ± 0.13 mm, along with biofilm inhibition activity. The formulation demonstrated antioxidant activity (5.21 µg/mL) and increased cell viability (90–95%) while maintaining low cytotoxicity in HSE-2 cells. A histopathological analysis confirmed that treatment with the nanocarriers reduced the levels of pro-inflammatory cytokines (IL-1β, TNF-α, TLR4, IL-6) and raised the levels of antioxidant markers (Nrf-2, SOD) in an in vivo rat model of otitis media. Conclusions: GO-based nanocarriers integrated into a neem oil double emulsion and coated with PLGA-Alg hydrogel deliver hesperidin with sustained release and enhanced antibacterial, antifungal, and antioxidant properties. This formulation may be used to treat otitis media and other oxidative stress diseases. Full article
(This article belongs to the Special Issue Progress of Hydrogel Applications in Novel Drug Delivery Platforms)
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18 pages, 4157 KiB  
Article
Hot Melt Extrusion as Continuous Manufacturing Technique to Produce Bilayer Films Loaded with Paracetamol or Lactase
by Friederike Brokmann, Katharina Luthe, Jonas Hartmann, Laura Müller, Friederike Klammt, Carla Hoffmann, Werner Weitschies and Christoph Rosenbaum
Pharmaceuticals 2025, 18(3), 310; https://doi.org/10.3390/ph18030310 - 24 Feb 2025
Viewed by 736
Abstract
Background/Objectives: The oral delivery of large-molecule drugs remains challenging due to poor solubility, perdemeability, and stability in the gastrointestinal tract, resulting in low bioavailability. In this study, hot melt extrusion (HME) was investigated as a solvent-free manufacturing technique for mucoadhesive bilayer films [...] Read more.
Background/Objectives: The oral delivery of large-molecule drugs remains challenging due to poor solubility, perdemeability, and stability in the gastrointestinal tract, resulting in low bioavailability. In this study, hot melt extrusion (HME) was investigated as a solvent-free manufacturing technique for mucoadhesive bilayer films to improve drug absorption. Methods: Polyvinyl alcohol (PVA) and polyethylene oxide (PEO) were evaluated as mucoadhesive film-forming polymers, in conjunction with Eudragit® RS as a water-insoluble backing layer. Paracetamol and lactase were utilized as small and large molecule APIs, respectively. The resulting films were assembled into bilayer film samples and examined for mechanical properties, mucoadhesion, and dissolution behavior. A novel dissolution model was developed to evaluate unidirectional drug transport. Results: The results showed that bilayer films could be successfully fabricated using HME, with different mechanical properties depending on the polymer and drug content. Tests with the newly developed dissolution model showed a unidirectional drug release. The model also confirmed the need for biorelevant dissolution test systems because of a better differentiation between polymers compared to standard test methods such as the paddle-over-disk method. Furthermore, the investigation revealed that the activity of enzymes was retained after extrusion, thus indicating the feasibility of processing biologics. Conclusions: This study highlights the potential of HME to produce bilayer films as an innovative drug delivery platform offering improved bioavailability for both small and large molecules. Full article
(This article belongs to the Special Issue Progress of Hydrogel Applications in Novel Drug Delivery Platforms)
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19 pages, 8091 KiB  
Article
The Role of Freeze-Drying as a Multifunctional Process in Improving the Properties of Hydrogels for Medical Use
by Kacper Odziomek, Anna K. Drabczyk, Paulina Kościelniak, Patryk Konieczny, Mateusz Barczewski and Katarzyna Bialik-Wąs
Pharmaceuticals 2024, 17(11), 1512; https://doi.org/10.3390/ph17111512 - 10 Nov 2024
Cited by 2 | Viewed by 2564
Abstract
Background/Objectives: Freeze-drying is a dehydration method that extends the shelf life and stability of drugs, vaccines, and biologics. Recently, its role has expanded beyond preservation to improve novel pharmaceuticals and their carriers, such as hydrogels, which are widely studied for both drug delivery [...] Read more.
Background/Objectives: Freeze-drying is a dehydration method that extends the shelf life and stability of drugs, vaccines, and biologics. Recently, its role has expanded beyond preservation to improve novel pharmaceuticals and their carriers, such as hydrogels, which are widely studied for both drug delivery and wound healing. The main aim of this study was to explore the multifunctional role of freeze-drying in improving the physicochemical properties of sodium alginate/poly(vinyl alcohol)-based hydrogels for medical applications. Methods: The base matrix and hydrogels containing a nanocarrier-drug system, were prepared by chemical cross-linking and then freeze-dried for 24 h at −53 °C under 0.2 mBa. Key analyses included determination of gel fraction, swelling ratio, FT-IR, SEM, TG/DTG, in vitro drug release and kinetics, and cytotoxicity assessment. Results: Freeze-drying caused an increase in the gel fraction of the hydrogel with the dual drug delivery system from 55 ± 1.6% to 72 ± 0.5%. Swelling ability was pH-dependent and remained in the same range (175–282%). Thermogravimetric analysis showed that freeze-dried hydrogels exhibited higher thermal stability than their non-freeze-dried equivalents. The temperature at 10% weight loss increased from 194.0 °C to 198.9 °C for the freeze-dried drug-loaded matrix, and from 188.4 °C to 203.1 °C for the freeze-dried drug-free matrix. The average pore size of the freeze-dried hydrogels was in the range of 1.07 µm ± 0.54 to 1.74 µm ± 0.92. In vitro drug release revealed that active substances were released in a controlled and prolonged way, according to the Korsmeyer–Peppas model. The cumulative amount of salicylic acid released at pH = 9.0 after 96 h was 63%, while that of fluocinolone acetonide reached 73%. Both hydrogels were non-toxic to human fibroblast cells, maintaining over 90% cell viability after 48 h of incubation. Conclusions: The results show a high potential for commercialisation of the obtained hydrogels as medical dressings. Full article
(This article belongs to the Special Issue Progress of Hydrogel Applications in Novel Drug Delivery Platforms)
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