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Recent Advances in Gels Engineering for Drug Delivery (2nd Edition)
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Recent Advances in Gels Engineering for Drug Delivery (2nd Edition)

A special issue of Gels (ISSN 2310-2861). This special issue belongs to the section "Gel Applications".

Deadline for manuscript submissions: 30 July 2025 | Viewed by 11923

Special Issue Editors

Dr. Mireia Mallandrich Miret

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Guest Editor
Department of Pharmacy, Pharmaceutical Technology and Physical Chemistry, Faculty of Pharmacy and Food Sciences, University of Barcelona, 08028 Barcelona, Spain
Interests: nanocarriers; topical drug delivery systems; dermal absorption; skin models; in vitro studies; nanomedicine; transdermal delivery; transmucosal delivery; cronocosmetic; skin biodistribution
Special Issues, Collections and Topics in MDPI journals
Dr. Francisco Fernández-Campos

E-Mail Website
Guest Editor
R&D Department, Labiana Pharmaceuticals, 08757 Corbera Llobregat, Barcelona, Spain
Interests: nanotechnology; molecular mechanism of anti-inflammatory drugs; antibiotics and antifungals; drug delivery systems; topical inflammatory diseases; pharmacokinetics
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Gels and nanogels are promising drug delivery systems for different administration routes (oral, parenteral, or topical) due to their biocompatibility and biodegradability, both of which allow for the modification of biological properties and pharmacokinetic profiles. Advances in polymer sciences and structural modifications of polymers imbue nanogels with intriguing properties; these may include responsiveness to different stimuli (pH, temperature, ionic strength, endogenous compounds, etc.), improved adhesion to biological surfaces, and improved anti-microbiological properties among others. In addition, advances in gel-manufacturing processes could improve the efficiency of these drug delivery systems and present a more realistic approach to administration to real patients.

We propose this Special Issue “Recent Advances in Gels Engineering for Drug Delivery (2nd Edition)”, to present up-to-date information about the potential use of gels and nanogels for treating different diseases and to collate novel approaches (including new manufacturing and composition properties), focusing mainly on biomedical applications. Both research articles and review manuscripts are welcome.

Dr. Mireia Mallandrich Miret
Dr. Francisco Fernández-Campos
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. Gels 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 2100 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

  • gels and nanogels
  • drug delivery
  • biomedical applications
  • topical administration
  • oral administration
  • parenteral administration
  • stimuli-responsive gels

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Related Special Issue

Published Papers (10 papers)

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Research

Jump to: Review

29 pages, 6444 KiB  
Article
Novel Gels for Post-Piercing Care: Evaluating the Efficacy of Pranoprofen Formulations in Reducing Inflammation
by Negar Ahmadi, Maria Rincón, Mireia Mallandrich, Joaquim Suñer-Carbó, Lilian Sosa, Mireya Zelaya, Sergio Martinez-Ruiz, Cecilia Cordero and Ana C. Calpena
Gels 2025, 11(5), 334; https://doi.org/10.3390/gels11050334 - 30 Apr 2025
Viewed by 420
Abstract
Mild to moderate pain for a few hours to several days post-piercing is normal, and the pain is usually accompanied by swelling, redness, and warmth due to the inflammatory response. Cool compresses and over-the-counter analgesics (e.g., NSAIDs) can ease mild discomfort. However, oral [...] Read more.
Mild to moderate pain for a few hours to several days post-piercing is normal, and the pain is usually accompanied by swelling, redness, and warmth due to the inflammatory response. Cool compresses and over-the-counter analgesics (e.g., NSAIDs) can ease mild discomfort. However, oral NSAIDs may have systemic side effects; for this reason, we propose a topical anti-inflammatory approach. Four pranoprofen-loaded gels were created using different gelling agents: Sepigel® 305 (PF-Gel-Sep), Carbopol® 940 (PF-Gel-Car), Pluronic® F-68 (PF-Gel-Plu), and Lutrol® F-127 (PF-Gel-Lut). The gels were assessed for pH, morphology, FT-IR spectroscopy, rheological properties, spreadability, swelling and degradation, drug release kinetics, skin permeation (cow and human skin), irritation potential (HET-CAM assay), and impact on skin barrier function (TEWL and SCH). The gels exhibited varied rheological properties with PF-Gel-Car showing high viscosity and PF-Gel-Plu very low viscosity. All gels had similar spreadability with PF-Gel-Lut showing the highest. PF-Gel-Car showed the highest amounts of PF released, whereas PF-Gel-Plu led to the highest amount of pranoprofen retained in human and bovine skin. The HET-CAM assay indicated that none of the PF-Gels were irritating. Additionally, PF-Gel-Car and PF-Gel-Plu showed no cytotoxic effects on HaCaT cells. In vivo testing on mice showed that PF-Gel-Car prevented inflammation, while the rest of the gels were able to revert it in 25 min. Skin tolerance tests revealed the gels did not affect TEWL, and some gels improved SCH. The study successfully formulated and characterized four PF-loaded topical gels with potential to be used as an alternative for treating inflammation from piercings and ear tags. Full article
(This article belongs to the Special Issue Recent Advances in Gels Engineering for Drug Delivery (2nd Edition))
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13 pages, 2615 KiB  
Article
Formulation of Caffeine–Hydroxypropyl-β-Cyclodextrin Complex in Hydrogel for Skin Treatment
by Lyubomira Radeva, Eleftheria Kalampalika, Yordan Yordanov, Petar D. Petrov, Virginia Tzankova and Krassimira Yoncheva
Gels 2025, 11(5), 326; https://doi.org/10.3390/gels11050326 - 27 Apr 2025
Viewed by 389
Abstract
Caffeine is a well-known xanthine that possesses antioxidant effects that could contribute to its application in different skin disorders. In order to enhance its effects, approaches for improving its permeation and penetration through skin layers could be applied. This study emphasizes the preparation [...] Read more.
Caffeine is a well-known xanthine that possesses antioxidant effects that could contribute to its application in different skin disorders. In order to enhance its effects, approaches for improving its permeation and penetration through skin layers could be applied. This study emphasizes the preparation of caffeine–cyclodextrin complex and its formulation in carbopol hydrogel. The complex was developed at a 1:1 molar ratio between caffeine and hydroxypropyl-β-cyclodextrin. It was found that the complex enhanced the radical scavenging activity of caffeine against ABTS radical as well as the protective effects against H2O2-induced oxidative stress in L929 fibroblasts. Then, the complex was formulated in hydrogel by applying 1% carbopol. The spreadability and penetration of the loaded hydrogel were improved in comparison with the empty hydrogel. The results revealed that the system could be appropriate for therapies of skin disorders, and its wound healing abilities could be further investigated. Full article
(This article belongs to the Special Issue Recent Advances in Gels Engineering for Drug Delivery (2nd Edition))
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21 pages, 4544 KiB  
Article
Injectable Magnetic-Nanozyme Based Thermosensitive Hydrogel for Multimodal DLBCL Therapy
by Min Yan, Jingcui Peng, Haoan Wu, Ming Ma and Yu Zhang
Gels 2025, 11(3), 218; https://doi.org/10.3390/gels11030218 - 20 Mar 2025
Viewed by 475
Abstract
Diffuse large B-cell lymphoma (DLBCL), accounting for 31% of non-Hodgkin lymphomas, remains recalcitrant to conventional therapies due to chemoresistance, metastatic progression, and immunosuppressive microenvironments. We report a novel injectable Fe3O4@DMSA@Pt@PLGA-PEG-PLGA hydrogel system integrating magnetothermal therapy (MHT), chemodynamic therapy (CDT), [...] Read more.
Diffuse large B-cell lymphoma (DLBCL), accounting for 31% of non-Hodgkin lymphomas, remains recalcitrant to conventional therapies due to chemoresistance, metastatic progression, and immunosuppressive microenvironments. We report a novel injectable Fe3O4@DMSA@Pt@PLGA-PEG-PLGA hydrogel system integrating magnetothermal therapy (MHT), chemodynamic therapy (CDT), and immunomodulation. Under alternating magnetic fields (AMF), the system achieves rapid therapeutic hyperthermia (50 °C within 7 min) while activating pH/temperature-dual responsive peroxidase (POD) -like activity in Fe3O4@DMSA@Pt nanoparticles. Catalytic efficiency under tumor-mimetic conditions was significantly higher than Fe3O4@DMSA controls, generating elevated reactive oxygen species (ROS). Flow cytometry revealed 75.9% apoptotic cell death in A20 lymphoma cells at 50 °C, significantly surpassing CDT alone (24.5%). Importantly, this dual mechanism induced immunogenic cell death (ICD) characterized by 4.1-fold CRT externalization, 68% HMGB1 nuclear depletion, and 40.74 nM ATP secretion. This triggered robust dendritic cell maturation (92% CD86+/CD80+ DCs comparable to LPS controls) and T cell activation (16.9% CD25+/CD69+ ratio, 130-fold baseline). Our findings validate the therapeutic potential of magnetothermal-chemodynamic synergy for DLBCL treatment, paving the way for innovative multi-mechanism therapeutic strategies against DLBCL with potential clinical translation prospects. Full article
(This article belongs to the Special Issue Recent Advances in Gels Engineering for Drug Delivery (2nd Edition))
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19 pages, 5187 KiB  
Article
Self-Healing Hydrogels with Intrinsic Antioxidant and Antibacterial Properties Based on Oxidized Hydroxybutanoyl Glycan and Quaternized Carboxymethyl Chitosan for pH-Responsive Drug Delivery
by Jae-pil Jeong, Kyungho Kim, Eunkyung Oh, Sohyun Park and Seunho Jung
Gels 2025, 11(3), 169; https://doi.org/10.3390/gels11030169 - 26 Feb 2025
Viewed by 649
Abstract
In this study, self-healing hydrogels were created using oxidized hydroxybutanoyl glycan (OHbG) and quaternized carboxymethyl chitosan (QCMCS), displaying antioxidant and antibacterial properties for pH-responsive drug delivery. The structures of the modified polysaccharides were confirmed through 1H NMR analysis. Double crosslinking in the [...] Read more.
In this study, self-healing hydrogels were created using oxidized hydroxybutanoyl glycan (OHbG) and quaternized carboxymethyl chitosan (QCMCS), displaying antioxidant and antibacterial properties for pH-responsive drug delivery. The structures of the modified polysaccharides were confirmed through 1H NMR analysis. Double crosslinking in the hydrogel occurred via imine bonds (between the aldehyde group of OHbG and the amine group of QCMCS) and ionic interactions (between the carboxyl group of OHbG and the quaternized group of QCMCS). The hydrogel exhibited self-healing properties and improved thermal stability with an increase in OHbG concentration. The OHbG/QCMCS hydrogel demonstrated high compressive strength, significant swelling, and large pore size. Drug release profiles varied between pH 2.0 (96.57%) and pH 7.4 (63.22%). Additionally, the hydrogel displayed antioxidant and antibacterial effects without compromising the polysaccharides’ inherent characteristics. No cytotoxicity was observed in any hydrogel samples. These findings indicate that the OHbG/QCMCS hydrogel is a biocompatible and stimuli-responsive drug carrier, with potential for various pharmaceutical, biomedical, and biotechnological applications. Full article
(This article belongs to the Special Issue Recent Advances in Gels Engineering for Drug Delivery (2nd Edition))
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20 pages, 2143 KiB  
Article
Thermosensitive In Situ Ophthalmic Gel for Effective Local Delivery and Antifungal Activity of Ketoconazole Nanoparticles
by Chutima Chaiwut, Sarin Tadtong, Puriputt Akachaipaibul, Jutamas Jiaranaikulwanitch, Sudarshan Singh, Siriporn Okonogi, Dwi Marlina Syukri and Chuda Chittasupho
Gels 2025, 11(1), 13; https://doi.org/10.3390/gels11010013 - 27 Dec 2024
Cited by 1 | Viewed by 1136
Abstract
Fungal keratitis is a severe ocular infection caused by pathogenic fungi, leading to potential vision loss if untreated. Current antifungal treatments face limitations such as low solubility, poor corneal penetration, and limited therapeutic options. This study aimed to develop a thermosensitive in situ [...] Read more.
Fungal keratitis is a severe ocular infection caused by pathogenic fungi, leading to potential vision loss if untreated. Current antifungal treatments face limitations such as low solubility, poor corneal penetration, and limited therapeutic options. This study aimed to develop a thermosensitive in situ gel incorporating ketoconazole nanoparticles (NPs) to enhance drug solubility, stability, and antifungal activity. Ketoconazole NPs were prepared using the solvent displacement method, achieving a particle size of 198.25 ± 27.51 nm, encapsulation efficiency of 94.08 ± 0.51%, polydispersity index of 0.42 ± 0.08, and a positive zeta potential value of +10.08 ± 0.19 mV. The NPs exhibited sustained zero-order release kinetics. The optimized NPs were incorporated into a poloxamer-based in situ gel, demonstrating a gelation temperature of 34.67 ± 0.58 °C and the shortest gelation time. The formulation provided a 5-fold increase in solubility and a 10-fold improvement in drug release compared to pure ketoconazole. Stability studies confirmed the gel retained its physicochemical and rheological properties for three months under various storage conditions. The in situ gel showed sustained release, effective antifungal activity against Malassezia furfur, and good tolerability, suggesting it as a promising alternative for treating fungal keratitis with improved bioavailability and patient compliance. Full article
(This article belongs to the Special Issue Recent Advances in Gels Engineering for Drug Delivery (2nd Edition))
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18 pages, 7511 KiB  
Article
Engineering 3D Printed Gummies Loaded with Metformin for Paediatric Use
by Karla J. Santamaría, Brayan J. Anaya, Aikaterini Lalatsa, Patricia González-Barranco, Lucía Cantú-Cárdenas and Dolores R. Serrano
Gels 2024, 10(10), 620; https://doi.org/10.3390/gels10100620 - 26 Sep 2024
Cited by 5 | Viewed by 2600
Abstract
In today’s pharmaceutical landscape, there’s an urgent need to develop new drug delivery systems that are appealing and effective in ensuring therapeutic adherence, particularly among paediatric patients. The advent of 3D printing in medicine is revolutionizing this space by enabling the creation of [...] Read more.
In today’s pharmaceutical landscape, there’s an urgent need to develop new drug delivery systems that are appealing and effective in ensuring therapeutic adherence, particularly among paediatric patients. The advent of 3D printing in medicine is revolutionizing this space by enabling the creation of precise, customizable, and visually appealing dosage forms. In this study, we produced 250 mg metformin paediatric gummies based on the semi-solid extrusion (SSE) 3D printing technique. A pharmaceutical ink containing metformin was successfully formulated with optimal flow properties suitable for room-temperature printing. Using a quality by design approach, 3D printing and casting methodologies were compared. The 3D-printed gummies exhibited better firmness and sustained release at earlier times to avoid metformin release in the oral cavity and ensure palatability. The texture and physical appearance match those of gummies commercially available. In conclusion, SSE allowed for the successful manufacture of 3D-printed sugar-free gummies for the treatment of diabetes mellitus for paediatric patients and is an easily translatable approach to clinical practice. Full article
(This article belongs to the Special Issue Recent Advances in Gels Engineering for Drug Delivery (2nd Edition))
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17 pages, 4178 KiB  
Article
Elastin-Derived Peptide-Based Hydrogels as a Potential Drug Delivery System
by Othman Al Musaimi, Keng Wooi Ng, Varshitha Gavva, Oscar M. Mercado-Valenzo, Hajira Banu Haroon and Daryl R. Williams
Gels 2024, 10(8), 531; https://doi.org/10.3390/gels10080531 - 12 Aug 2024
Cited by 1 | Viewed by 2999
Abstract
A peptide-based hydrogel sequence was computationally predicted from the Ala-rich cross-linked domains of elastin. Three candidate peptides were subsequently synthesised and characterised as potential drug delivery vehicles. The elastin-derived peptides are Fmoc-FFAAAAKAA-NH2, Fmoc-FFAAAKAA-NH2, and Fmoc-FFAAAKAAA-NH2. All three [...] Read more.
A peptide-based hydrogel sequence was computationally predicted from the Ala-rich cross-linked domains of elastin. Three candidate peptides were subsequently synthesised and characterised as potential drug delivery vehicles. The elastin-derived peptides are Fmoc-FFAAAAKAA-NH2, Fmoc-FFAAAKAA-NH2, and Fmoc-FFAAAKAAA-NH2. All three peptide sequences were able to self-assemble into nanofibers. However, only the first two could form hydrogels, which are preferred as delivery systems compared to solutions. Both of these peptides also exhibited favourable nanofiber lengths of at least 1.86 and 4.57 µm, respectively, which are beneficial for the successful delivery and stability of drugs. The shorter fibre lengths of the third peptide (maximum 0.649 µm) could have inhibited their self-assembly into the three-dimensional networks crucial to hydrogel formation. Full article
(This article belongs to the Special Issue Recent Advances in Gels Engineering for Drug Delivery (2nd Edition))
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20 pages, 4199 KiB  
Article
Porphyrin Photosensitizers into Polysaccharide-Based Biopolymer Hydrogels for Topical Photodynamic Therapy: Physicochemical and Pharmacotechnical Assessments
by Andreea Mihaela Burloiu, Emma Adriana Ozon, Adina Magdalena Musuc, Mihai Anastasescu, Radu Petre Socoteanu, Irina Atkinson, Daniela C. Culita, Valentina Anuta, Ioana Andreea Popescu, Dumitru Lupuliasa, Dragoș Paul Mihai, Cerasela Elena Gîrd and Rica Boscencu
Gels 2024, 10(8), 499; https://doi.org/10.3390/gels10080499 - 27 Jul 2024
Cited by 2 | Viewed by 1514
Abstract
Photodynamic therapy (PDT) is an emerging treatment modality that utilizes light-sensitive compounds, known as photosensitizers, to produce reactive oxygen species (ROS) that can selectively destroy malignant or diseased tissues upon light activation. This study investigates the incorporation of two porphyrin structures, 5-(4-hydroxy-3-methoxyphenyl)-10,15,20-tris-(4-acetoxy-3-methoxyphenyl) porphyrin [...] Read more.
Photodynamic therapy (PDT) is an emerging treatment modality that utilizes light-sensitive compounds, known as photosensitizers, to produce reactive oxygen species (ROS) that can selectively destroy malignant or diseased tissues upon light activation. This study investigates the incorporation of two porphyrin structures, 5-(4-hydroxy-3-methoxyphenyl)-10,15,20-tris-(4-acetoxy-3-methoxyphenyl) porphyrin (P2.2.) and 5,10,15,20-tetrakis-(4-acetoxy-3-methoxyphenyl) porphyrin (P2.1.), into hydroxypropyl cellulose (HPC) hydrogels for potential use in topical photodynamic therapy (PDT). The structural and compositional properties of the resulting hydrogels were characterized using advanced techniques such as Fourier-transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD), thermogravimetric analysis (TGA), atomic force microscopy (AFM), UV-Visible (UV-Vis) spectroscopy, and fluorescence spectroscopy. FTIR spectra revealed a slight shift of the main characteristic absorption bands corresponding to the porphyrins and their interactions with the HPC matrix, indicating successful incorporation and potential hydrogen bonding. XRD patterns revealed the presence of crystalline domains within the HPC matrix, indicating partial crystallization of the porphyrins dispersed within the amorphous polymer structure. TGA results indicated enhanced thermal stability of the HPC–porphyrin gels compared to 10% HPC gel, with additional weight loss stages corresponding to the thermal degradation of the porphyrins. Rheological analysis showed that the gels exhibited pseudoplastic behavior and thixotropic properties, with minimal impact on the flow properties of HPC by P2.1., but notable changes in viscosity and shear stress with P2.2. incorporation, indicating structural modifications. AFM imaging revealed a homogeneous distribution of porphyrins, and UV-Vis and fluorescence spectroscopy confirmed the retention of their photophysical properties. Pharmacotechnical evaluations showed that the hydrogels possessed suitable mechanical properties, optimal pH, high swelling ratios, and excellent spreadability, making them ideal for topical application. These findings suggest that the porphyrin-incorporated HPC hydrogels have significant potential as effective therapeutic agents for topical applications. Full article
(This article belongs to the Special Issue Recent Advances in Gels Engineering for Drug Delivery (2nd Edition))
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Review

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26 pages, 2841 KiB  
Review
Modified Phospholipid Vesicular Gel for Transdermal Drug Delivery: The Influence of Glycerin and/or Ethanol on Their Lipid Bilayer Fluidity and Penetration Characteristics
by Marwa H. Abdallah, Mona M. Shahien, Hemat El-Sayed El-Horany and Enas Haridy Ahmed
Gels 2025, 11(5), 358; https://doi.org/10.3390/gels11050358 - 13 May 2025
Viewed by 252
Abstract
This review explores the enhanced transdermal therapy of several skin disorders with the application of carriers comprising phospholipid vesicular gel systems. Topical drug delivery has several advantages compared to other administration methods, including enhanced patient compliance, the avoidance of the first-pass impact associated [...] Read more.
This review explores the enhanced transdermal therapy of several skin disorders with the application of carriers comprising phospholipid vesicular gel systems. Topical drug delivery has several advantages compared to other administration methods, including enhanced patient compliance, the avoidance of the first-pass impact associated with oral administration, and the elimination of the need for repeated doses. Nonetheless, the skin barrier obstructs the penetration of drugs, hence affecting its therapeutic efficacy. Carriers with phospholipid soft vesicles comprise a novel strategy used to augment drug delivery into the skin and boost therapeutic efficacy. These vesicles encompass chemicals that possess the ability to fluidize phospholipid bilayers, producing a pliable vesicle that facilitates penetration into the deeper layers of the skin. Phospholipid-based vesicular carriers have been extensively studied for improved drug delivery through dermal and transdermal pathways. Traditional liposomes are limited to the stratum corneum of the skin and do not penetrate the deeper layers. Ethosomes, glycerosomes, and glycethosomes are nanovesicular systems composed of ethanol, glycerol, or a combination of ethanol and glycerol, respectively. Their composition produce pliable vesicles by fluidizing the phospholipid bilayers, facilitating deeper penetration into the skin. This article examines the impact of ethanol and glycerol on phospholipid vesicles, and outlines their respective manufacturing techniques. Thus far, these discrepancies have not been analyzed comparatively. The review details several active compounds integrated into these nanovesicular gel systems and examined through in vitro, in vivo, or clinical human trials involving compositions with various active molecules for the treatment of various dermatological conditions. Full article
(This article belongs to the Special Issue Recent Advances in Gels Engineering for Drug Delivery (2nd Edition))
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30 pages, 1375 KiB  
Review
Post-Stroke Recovery: A Review of Hydrogel-Based Phytochemical Delivery Systems
by Irina Musa, Alexandra Daniela Rotaru-Zavaleanu, Veronica Sfredel, Madalina Aldea, Andrei Gresita and Daniela Gabriela Glavan
Gels 2025, 11(4), 260; https://doi.org/10.3390/gels11040260 - 1 Apr 2025
Viewed by 758
Abstract
Stroke remains a leading cause of disability worldwide, underscoring the urgent need for novel and innovative therapeutic strategies to enhance neuroprotection, support regeneration, and improve functional recovery. Previous research has shown that phytochemicals such as curcumin, tannic acid, gallic acid, ginsenosides, resveratrol, and [...] Read more.
Stroke remains a leading cause of disability worldwide, underscoring the urgent need for novel and innovative therapeutic strategies to enhance neuroprotection, support regeneration, and improve functional recovery. Previous research has shown that phytochemicals such as curcumin, tannic acid, gallic acid, ginsenosides, resveratrol, and isorhamnetin display extensive neuroprotective properties, including antioxidant, anti-inflammatory, and anti-apoptotic effects. These natural compounds could also promote neurogenesis, angiogenesis, and the preservation of the blood–brain barrier. Despite their promising bioactivities, clinical application is often limited by poor solubility, bioavailability, and suboptimal pharmacokinetics. Hydrogels offer a promising solution by encapsulating and controlling the gradual release of these phytochemicals directly at the site of injury. Recent advancements in hydrogel formulations, constructed from biopolymers and functionalized using nanotechnological approaches, could significantly improve the solubility, stability, and targeted delivery of phytochemicals. Controlled release profiles from pH-sensitive and environment-responsive hydrogels could ensure that the compounds’ therapeutic effects are optimally timed with individual and critical stages of post-stroke repair. Moreover, hydrogel scaffolds with tailored material properties and biocompatibility can create a favorable microenvironment, reducing secondary inflammation, enhancing tissue regeneration, and potentially improving functional and cognitive outcomes following stroke. This review explores the potential of integrating phytochemicals within hydrogel-based delivery systems specifically designed for post-stroke recovery. The design and synthesis of biocompatible, biodegradable hydrogels functionalized especially with phytochemicals and their applications are also discussed. Lastly, we emphasize the need for additional robust and translatable preclinical studies. Full article
(This article belongs to the Special Issue Recent Advances in Gels Engineering for Drug Delivery (2nd Edition))
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