Rational Design and Characterization of Hydrogels to Improve Pharmaceutical and Biomedical Applicability

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

Deadline for manuscript submissions: closed (20 May 2022) | Viewed by 34099

Special Issue Editors


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Guest Editor
Department of Chemistry and Technology of Drugs, University of Rome Sapienza, Roma, Italy
Interests: hydrogels; drug delivery; composite systems; polysaccharides; rheomechanical properties of hydrogels; micro- and nanoparticulate delivery systems
Special Issues, Collections and Topics in MDPI journals

E-Mail Website
Guest Editor
Department of Drug Chemistry and Technologies; Sapienza University of Rome, Rome, Italy
Interests: hydrogels; drug delivery; composite systems; polysaccharides; rheomechanical properties of hydrogels; micro and nanoparticulate delivery systems
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

In their pioneering 1960 work, Wichterle and Lim were the first to describe a hydrogel system for biomedical application. Since then, many other hydrogels have been proposed for application not only in the biomedical, but also in the pharmaceutical field, as drug delivery systems.

There has been a continuous effort to design innovative and smart gel-based systems to overcome the limitations of classical hydrogels, provide them with tailored features, and further extend their applicability in both pharmaceutical and biomedical fields. Significant progress has been made in improving the properties of hydrogels, but several challenges still remain to improve their clinical applicability. Many advances have derived from the more rational design and characterization of hydrogels, as it has become clear over the years that different physicochemical, biological, mechanical, and structural properties are needed depending on the final application intended for the specific hydrogel system.

This Special Issue serves to highlight and capture the contemporary progress and current landscape of three-dimensional networks made of interconnected hydrophilic polymer chains, including but not limited to hydrogels, cryogels, surgical adhesives, biomimetic hydrogels, smart hydrogels, self-healing hydrogels, composite hydrogels, bioinks, double-network and other interpenetrated and semi-interpenetrated hydrogels. We invite original and review articles on all aspects of the design, development, fabrication, characterization, and modeling of hydrogel systems for application in pharmacy and biomedicine, including tissue engineering and regenerative medicine.

Prof. Patrizia Paolicelli
Prof. Maria Antonietta Casadei
Guest Editors

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Keywords

  • hydrogels
  • cryogels
  • drug delivery
  • surgical adhesives
  • biomimetic hydrogels
  • smart hydrogels
  • self-healing hydrogels
  • bioinks
  • composite hydrogels
  • interpenetrated and semi-interpenetrated hydrogels

Published Papers (8 papers)

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Research

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18 pages, 8399 KiB  
Article
Tissue Adhesive, Self-Healing, Biocompatible, Hemostasis, and Antibacterial Properties of Fungal-Derived Carboxymethyl Chitosan-Polydopamine Hydrogels
by Kummara Madhusudana Rao, Kannan Badri Narayanan, Uluvangada Thammaiah Uthappa, Pil-Hoon Park, Inho Choi and Sung Soo Han
Pharmaceutics 2022, 14(5), 1028; https://doi.org/10.3390/pharmaceutics14051028 - 10 May 2022
Cited by 25 | Viewed by 3436
Abstract
In this work, fungal mushroom-derived carboxymethyl chitosan-polydopamine hydrogels (FCMCS-PDA) with multifunctionality (tissue adhesive, hemostasis, self-healing, and antibacterial properties) were developed for wound dressing applications. The hydrogel is obtained through dynamic Schiff base cross-linking and hydrogen bonds between FCMCS-PDA and covalently cross-linked polyacrylamide (PAM) [...] Read more.
In this work, fungal mushroom-derived carboxymethyl chitosan-polydopamine hydrogels (FCMCS-PDA) with multifunctionality (tissue adhesive, hemostasis, self-healing, and antibacterial properties) were developed for wound dressing applications. The hydrogel is obtained through dynamic Schiff base cross-linking and hydrogen bonds between FCMCS-PDA and covalently cross-linked polyacrylamide (PAM) networks. The FCMCS-PDA-PAM hydrogels have a good swelling ratio, biodegradable properties, excellent mechanical properties, and a highly interconnected porous structure with PDA microfibrils. Interestingly, the PDA microfibrils were formed along with FCMCS fibers in the hydrogel networks, which has a high impact on the biological performance of hydrogels. The maximum adhesion strength of the hydrogel to porcine skin was achieved at about 29.6 ± 2.9 kPa. The hydrogel had good self-healing and recoverable properties. The PDA-containing hydrogels show good antibacterial properties on Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) bacteria. Moreover, the adhesive hydrogels depicted good viability and attachment of skin fibroblasts and keratinocyte cells. Importantly, FCMCS and PDA combined resulted in fast blood coagulation within 60 s. Hence, the adhesive hydrogel with multifunctionality has excellent potential as a wound dressing material for infected wounds. Full article
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18 pages, 2607 KiB  
Article
Modulation of Conductivity of Alginate Hydrogels Containing Reduced Graphene Oxide through the Addition of Proteins
by Ahmed Raslan, Jesús Ciriza, Ana María Ochoa de Retana, María Luisa Sanjuán, Muhammet S. Toprak, Patricia Galvez-Martin, Laura Saenz-del-Burgo and Jose Luis Pedraz
Pharmaceutics 2021, 13(9), 1473; https://doi.org/10.3390/pharmaceutics13091473 - 15 Sep 2021
Cited by 5 | Viewed by 2398
Abstract
Modifying hydrogels in order to enhance their conductivity is an exciting field with applications in cardio and neuro-regenerative medicine. Therefore, we have designed hybrid alginate hydrogels containing uncoated and protein-coated reduced graphene oxide (rGO). We specifically studied the adsorption of three different proteins, [...] Read more.
Modifying hydrogels in order to enhance their conductivity is an exciting field with applications in cardio and neuro-regenerative medicine. Therefore, we have designed hybrid alginate hydrogels containing uncoated and protein-coated reduced graphene oxide (rGO). We specifically studied the adsorption of three different proteins, BSA, elastin, and collagen, and the outcomes when these protein-coated rGO nanocomposites are embedded within the hydrogels. Our results demonstrate that BSA, elastin, and collagen are adsorbed onto the rGO surface, through a non-spontaneous phenomenon that fits Langmuir and pseudo-second-order adsorption models. Protein-coated rGOs are able to preclude further adsorption of erythropoietin, but not insulin. Collagen showed better adsorption capacity than BSA and elastin due to its hydrophobic nature, although requiring more energy. Moreover, collagen-coated rGO hybrid alginate hydrogels showed an enhancement in conductivity, showing that it could be a promising conductive scaffold for regenerative medicine. Full article
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16 pages, 5684 KiB  
Article
Thermosensitive Bioadhesive Hydrogels Based on Poly(N-isopropylacrilamide) and Poly(methyl vinyl ether-alt-maleic anhydride) for the Controlled Release of Metronidazole in the Vaginal Environment
by Ana V. Torres-Figueroa, Cinthia J. Pérez-Martínez, J. Carmelo Encinas, Silvia Burruel-Ibarra, María I. Silvas-García, Alejandro M. García Alegría and Teresa del Castillo-Castro
Pharmaceutics 2021, 13(8), 1284; https://doi.org/10.3390/pharmaceutics13081284 - 17 Aug 2021
Cited by 8 | Viewed by 2763
Abstract
The development of thermosensitive bioadhesive hydrogels as multifunctional platforms for the controlled delivery of microbicides is a valuable contribution for the in situ treatment of vagina infections. In this work, novel semi-interpenetrating network (s-IPN) hydrogels were prepared by the entrapment of linear poly(methyl [...] Read more.
The development of thermosensitive bioadhesive hydrogels as multifunctional platforms for the controlled delivery of microbicides is a valuable contribution for the in situ treatment of vagina infections. In this work, novel semi-interpenetrating network (s-IPN) hydrogels were prepared by the entrapment of linear poly(methyl vinyl ether-alt-maleic anhydride) (PVME-MA) chains within crosslinked 3D structures of poly(N-isopropylacrylamide) (PNIPAAm). The multifunctional platforms were characterized by Fourier transform infrared spectroscopy, scanning electron microscopy, thermal techniques, rheological analysis, swelling kinetic measurements, and bioadhesion tests on porcine skin. The hydrogels exhibited an interconnected porous structure with defined boundaries. An elastic, solid-like behavior was predominant in all formulations. The swelling kinetics were strongly dependent on temperature (25 °C and 37 °C) and pH (7.4 and 4.5) conditions. The s-IPN with the highest content of PVME-MA displayed a significantly higher detachment force (0.413 ± 0.014 N) than the rest of the systems. The metronidazole loading in the s-IPN improved its bioadhesiveness. In vitro experiments showed a sustained release of the antibiotic molecules from the s-IPN up to 48 h (94%) in a medium simulating vaginal fluid, at 37 °C. The thermosensitive and bioadhesive PNIPAAm/PVME-MA systems showed a promising performance for the controlled release of metronidazole in the vaginal environment. Full article
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24 pages, 4015 KiB  
Article
Hybrid 3D Printing of Advanced Hydrogel-Based Wound Dressings with Tailorable Properties
by Marko Milojević, Gregor Harih, Boštjan Vihar, Jernej Vajda, Lidija Gradišnik, Tanja Zidarič, Karin Stana Kleinschek, Uroš Maver and Tina Maver
Pharmaceutics 2021, 13(4), 564; https://doi.org/10.3390/pharmaceutics13040564 - 16 Apr 2021
Cited by 46 | Viewed by 4615
Abstract
Despite the extensive utilization of polysaccharide hydrogels in regenerative medicine, current fabrication methods fail to produce mechanically stable scaffolds using only hydrogels. The recently developed hybrid extrusion-based bioprinting process promises to resolve these current issues by facilitating the simultaneous printing of stiff thermoplastic [...] Read more.
Despite the extensive utilization of polysaccharide hydrogels in regenerative medicine, current fabrication methods fail to produce mechanically stable scaffolds using only hydrogels. The recently developed hybrid extrusion-based bioprinting process promises to resolve these current issues by facilitating the simultaneous printing of stiff thermoplastic polymers and softer hydrogels at different temperatures. Using layer-by-layer deposition, mechanically advantageous scaffolds can be produced by integrating the softer hydrogel matrix into a stiffer synthetic framework. This work demonstrates the fabrication of hybrid hydrogel-thermoplastic polymer scaffolds with tunable structural and chemical properties for applications in tissue engineering and regenerative medicine. Through an alternating deposition of polycaprolactone and alginate/carboxymethylcellulose gel strands, scaffolds with the desired architecture (e.g., filament thickness, pore size, macro-/microporosity), and rheological characteristics (e.g., swelling capacity, degradation rate, and wettability) were prepared. The hybrid fabrication approach allows the fine-tuning of wettability (approx. 50–75°), swelling (approx. 0–20× increased mass), degradability (approx. 2–30+ days), and mechanical strength (approx. 0.2–11 MPa) in the range between pure hydrogels and pure thermoplastic polymers, while providing a gradient of surface properties and good biocompatibility. The controlled degradability and permeability of the hydrogel component may also enable controlled drug delivery. Our work shows that the novel hybrid hydrogel-thermoplastic scaffolds with adjustable characteristics have immense potential for tissue engineering and can serve as templates for developing novel wound dressings. Full article
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22 pages, 6042 KiB  
Article
Semi-Crystalline Copolymer Hydrogels as Smart Drug Carriers: In Vitro Thermo-Responsive Naproxen Release Study
by Snežana Ilić-Stojanović, Ljubiša Nikolić, Vesna Nikolić, Slobodan Petrović, Violeta Oro, Žarko Mitić and Stevo Najman
Pharmaceutics 2021, 13(2), 158; https://doi.org/10.3390/pharmaceutics13020158 - 26 Jan 2021
Cited by 18 | Viewed by 2400
Abstract
In this study, poly(N-isopropylacrylamide-co-2-hydroxypropyl methacrylate) hydrogels were synthesized using free radical initiated copolymerization method. Four hydrogels with different cross-linker concentrations were prepared. Semi-crystalline, cross-linked copolymer networks were confirmed by FTIR, SEM and XRD analysis. Variation of swelling behaviour was [...] Read more.
In this study, poly(N-isopropylacrylamide-co-2-hydroxypropyl methacrylate) hydrogels were synthesized using free radical initiated copolymerization method. Four hydrogels with different cross-linker concentrations were prepared. Semi-crystalline, cross-linked copolymer networks were confirmed by FTIR, SEM and XRD analysis. Variation of swelling behaviour was monitored gravimetrically and thermo-responsiveness has been noticed. An application of synthesized thermo-responsive hydrogels as carriers for the modulated release of anti-inflammatory model drug was investigated. Moreover, naproxen loading into these hydrogels was also determined using FTIR, SEM and XRD techniques and release was analyzed using HPLC method at simulated physiological conditions. Swelling kinetic and mechanism of water transport, as well as diffusion of naproxen through the hydrogels were analyzed. Thus, the aim of this work was to study various compositions of obtained hydrogels and their possibility of application as a thermo-responsive carrier for prolonged naproxen release in order to evaluate as a potential candidate for drug carrier in future pharmaceutical applications. Full article
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Review

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19 pages, 3793 KiB  
Review
Immunomodulating Hydrogels as Stealth Platform for Drug Delivery Applications
by Zahra Rezaei, Dilara Yilmaz-Aykut, Fatima Mumtaza Tourk, Nicole Bassous, Margot Barroso-Zuppa, Asif Iqbal Shawl, Syed Salman Ashraf, Huseyin Avci and Shabir Hassan
Pharmaceutics 2022, 14(10), 2244; https://doi.org/10.3390/pharmaceutics14102244 - 21 Oct 2022
Cited by 4 | Viewed by 2201
Abstract
Non-targeted persistent immune activation or suppression by different drug delivery platforms can cause adverse and chronic physiological effects including cancer and arthritis. Therefore, non-toxic materials that do not trigger an immunogenic response during delivery are crucial for safe and effective in vivo treatment. [...] Read more.
Non-targeted persistent immune activation or suppression by different drug delivery platforms can cause adverse and chronic physiological effects including cancer and arthritis. Therefore, non-toxic materials that do not trigger an immunogenic response during delivery are crucial for safe and effective in vivo treatment. Hydrogels are excellent candidates that can be engineered to control immune responses by modulating biomolecule release/adsorption, improving regeneration of lymphoid tissues, and enhancing function during antigen presentation. This review discusses the aspects of hydrogel-based systems used as drug delivery platforms for various diseases. A detailed investigation on different immunomodulation strategies for various delivery options and deliberate upon the outlook of such drug delivery platforms are conducted. Full article
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57 pages, 5979 KiB  
Review
Advanced Functional Materials Based on Nanocellulose for Pharmaceutical/Medical Applications
by Raluca Nicu, Florin Ciolacu and Diana E. Ciolacu
Pharmaceutics 2021, 13(8), 1125; https://doi.org/10.3390/pharmaceutics13081125 - 23 Jul 2021
Cited by 41 | Viewed by 5028
Abstract
Nanocelluloses (NCs), with their remarkable characteristics, have proven to be one of the most promising “green” materials of our times and have received special attention from researchers in nanomaterials. A diversity of new functional materials with a wide range of biomedical applications has [...] Read more.
Nanocelluloses (NCs), with their remarkable characteristics, have proven to be one of the most promising “green” materials of our times and have received special attention from researchers in nanomaterials. A diversity of new functional materials with a wide range of biomedical applications has been designed based on the most desirable properties of NCs, such as biocompatibility, biodegradability, and their special physicochemical properties. In this context and under the pressure of rapid development of this field, it is imperative to synthesize the successes and the new requirements in a comprehensive review. The first part of this work provides a brief review of the characteristics of the NCs (cellulose nanocrystals—CNC, cellulose nanofibrils—CNF, and bacterial nanocellulose—BNC), as well as of the main functional materials based on NCs (hydrogels, nanogels, and nanocomposites). The second part presents an extensive review of research over the past five years on promising pharmaceutical and medical applications of nanocellulose-based materials, which have been discussed in three important areas: drug-delivery systems, materials for wound-healing applications, as well as tissue engineering. Finally, an in-depth assessment of the in vitro and in vivo cytotoxicity of NCs-based materials, as well as the challenges related to their biodegradability, is performed. Full article
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36 pages, 2641 KiB  
Review
Emerging Role of Hydrogels in Drug Delivery Systems, Tissue Engineering and Wound Management
by Shery Jacob, Anroop B. Nair, Jigar Shah, Nagaraja Sreeharsha, Sumeet Gupta and Pottathil Shinu
Pharmaceutics 2021, 13(3), 357; https://doi.org/10.3390/pharmaceutics13030357 - 08 Mar 2021
Cited by 144 | Viewed by 9985
Abstract
The popularity of hydrogels as biomaterials lies in their tunable physical properties, ability to encapsulate small molecules and macromolecular drugs, water holding capacity, flexibility, and controllable degradability. Functionalization strategies to overcome the deficiencies of conventional hydrogels and expand the role of advanced hydrogels [...] Read more.
The popularity of hydrogels as biomaterials lies in their tunable physical properties, ability to encapsulate small molecules and macromolecular drugs, water holding capacity, flexibility, and controllable degradability. Functionalization strategies to overcome the deficiencies of conventional hydrogels and expand the role of advanced hydrogels such as DNA hydrogels are extensively discussed in this review. Different types of cross-linking techniques, materials utilized, procedures, advantages, and disadvantages covering hydrogels are tabulated. The application of hydrogels, particularly in buccal, oral, vaginal, and transdermal drug delivery systems, are described. The review also focuses on composite hydrogels with enhanced properties that are being developed to meet the diverse demand of wound dressing materials. The unique advantages of hydrogel nanoparticles in targeted and intracellular delivery of various therapeutic agents are explained. Furthermore, different types of hydrogel-based materials utilized for tissue engineering applications and fabrication of contact lens are discussed. The article also provides an overview of selected examples of commercial products launched particularly in the area of oral and ocular drug delivery systems and wound dressing materials. Hydrogels can be prepared with a wide variety of properties, achieving biostable, bioresorbable, and biodegradable polymer matrices, whose mechanical properties and degree of swelling are tailored with a specific application. These unique features give them a promising future in the fields of drug delivery systems and applied biomedicine. Full article
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