Atopic dermatitis (AD) is a common disease-causing skin inflammation, redness, and irritation, which can eventually result in infection that drastically impacts patient quality of life. Resveratrol (Res) is a natural phytochemical famed for its excellent anti-inflammatory and antioxidant activities. However, it is poorly bioavailable. Thus, a drug delivery system is needed to enhance in vivo bioactivity. Herein, we report the preparation of hyaluronic acid (HA) hydrogels containing resveratrol-loaded chitosan (CS) nanoparticles, their physicochemical analysis, and their potential therapeutic effects in the treatment of AD. Positively charged CS nanoparticles prepared by tripolyphosphate (TPP) gelation showed sizes ranging from 120 to around 500 nm and Res encapsulation efficiency as high as 80%. Embedding the nanoparticles in HA retarded their hydrolytic degradation and also slowed resveratrol release. Resveratrol released from nanoparticle-loaded hydrogel counteracted the oxidative damage induced by ROS generation in TNF-α/INF-γ-treated human keratinocytes (HaCaT) used as an AD in vitro model. Moreover, pre-treatment with Res@gel reduced secretion and gene expression of proinflammatory cytokines in HaCaT cells. The physicochemical analysis and in vitro assay confirmed that the formulated hydrogel could be considered an efficient and sustained resveratrol delivery vector in AD treatment.

Polysaccharide-based hydrogels have emerged as indispensable materials in tissue engineering and wound healing, offering a unique combination of biocompatibility, biodegradability, and structural versatility. Indeed, their three-dimensional polymeric network and high water content closely resemble the natural extracellular matrix, creating a microenvironment for cell growth, differentiation, and tissue regeneration. Moreover, their intrinsic biodegradability, tunable chemical structure, non-toxicity, and minimal immunogenicity make them optimal candidates for prolonged drug delivery systems. Notwithstanding numerous advantages, these polysaccharide-based hydrogels are confronted with setbacks such as variability in material qualities depending on their source, susceptibility to microbial contamination, unregulated water absorption, inadequate mechanical strength, and unpredictable degradation patterns which limit their efficacy in real-world applications. This review summarizes recent advancements in the application of polysaccharide-based hydrogels, including cellulose, starch, pectin, zein, dextran, pullulan and hyaluronic acid as innovative solutions in wound healing, drug delivery, tissue engineering, and regenerative medicine. Future research should concentrate on optimizing hydrogel formulations to enhance their effectiveness in regenerative medicine and antimicrobial therapy.

Although osteoarthritis (OA) is a chronic inflammatory degenerative disease affecting millions of people worldwide, the current therapies are limited to palliative care and do not eliminate the necessity of surgical intervention in the most severe cases. Several dietary and nutraceutical factors, such as hydroxytyrosol (Hyt), have demonstrated beneficial effects in the prevention or treatment of OA both in vitro and in animal models. However, the therapeutic application of Hyt is limited due to its poor bioavailability following oral administration. In the present study, a localized drug delivery platform containing a combination of Hyt-loading chitosan nanoparticles (Hyt-NPs) and in situ forming hydrogel have been developed to obtain the benefits of both hydrogels and nanoparticles. This thermosensitive formulation, based on Pluronic F-127 (F-127), hyaluronic acid (HA) and Hyt-NPs (called Hyt@tgel) presents the unique ability to be injected in a minimally invasive way into a target region as a freely flowing solution at room temperature forming a gel at body temperature. The Hyt@tgel system showed reduced oxidative and inflammatory effects in the chondrocyte cellular model as well as a reduction in senescent cells after induction with H₂O₂. In addition, Hyt@tgel influenced chondrocytes gene expression under pathological state maintaining their metabolic activity and limiting the expression of critical OA-related genes in human chondrocytes treated with stressors promoting OA-like features. Hence, it can be concluded that the formulated hydrogel injection could be proposed for the efficient and sustained Hyt delivery for OA treatment. The next step would be the extraction of “added-value” bioactive polyphenols from by-products of the olive industry, in order to develop a green delivery system able not only to enhance the human wellbeing but also to promote a sustainable environment.

Marine polysaccharide hydrogels have emerged as an innovative platform for regulating the in vivo release of natural bioactive compounds for medical purposes. These hydrogels, which have exceptional biocompatibility, biodegradability, and high water absorption capacity, create effective matrices for encapsulating different bioactive molecules. In addition, by modifying the physical and chemical properties of marine hydrogels, including cross-linking density, swelling behavior, and response to external stimuli like pH, temperature, or ionic strength, the release profile of encapsulated bioactive compounds is strictly regulated, thus maximizing therapeutic efficacy and minimizing side effects. Finally, by using naturally sourced polysaccharides in hydrogel formulations, sustainability is promoted by reducing dependence on synthetic polymers, meeting the growing demand for eco-friendly materials. This review analyzes the interaction between marine polysaccharide hydrogels and encapsulating compounds and offers examples of how bioactive molecules can be encapsulated, released, and stabilized.

Stimuli-responsive nanocomposite gels combine the unique properties of hydrogels with those of nanoparticles, thus avoiding the suboptimal results of single components and creating versatile, multi-functional platforms for therapeutic and diagnostic applications. These hybrid materials are engineered to respond to various internal and external stimuli, such as temperature, pH, light, magnetic fields, and enzymatic activity, allowing precise control over drug release, tissue regeneration, and biosensing. Their responsiveness to environmental cues permits personalized medicine approaches, providing dynamic control over therapeutic interventions and real-time diagnostic capabilities. This review explores recent advances in stimuli-responsive hybrid gels’ synthesis and application, including drug delivery, tissue engineering, and diagnostics. Overall, these platforms have significant clinical potential, and future research is expected to lead to unique solutions to address unmet medical needs.

Extracellular vesicles (EVs) have gained increasing attention in recent years as a valuable focus of scientific investigation, owing to their potential therapeutic properties and wide-ranging uses in medicine. EVs are a heterogeneous population of membrane-enclosed vesicles with lipid bilayers, released by cells from both animal and plant origins. These widespread vesicles play a crucial role in cell-to-cell communication and serve as carriers for a variety of biomolecules such as proteins, lipids, and nucleic acids. The most common method of classifying EVs is based on their biogenesis pathway, distinguishing exosomes, microvesicles, and apoptotic bodies as the major types. In recent years, there has been a growing interest in PDEs, as they offer a practical and eco-friendly alternative to exosomes sourced from mammals. Mounting data from both laboratory-based and animal model experiments indicate that PDEs have natural therapeutic properties that modulate biological activities within cells, demonstrating properties such as anti-inflammatory, antioxidant, and anticancer effects that may aid in treating diseases and enhancing human well-being. Moreover, PDEs hold promise as reliable and biologically compatible carriers for drug delivery. Although studies conducted before clinical trials have yielded encouraging results, numerous unresolved issues and gaps in understanding remain, which must be resolved to facilitate the effective advancement of PDEs toward medical use in human patients. A key concern is the absence of unified procedures for processing materials and for obtaining PDEs from different botanical sources. This article provides a comprehensive summary of existing findings on PDEs, critically examining the hurdles they face, and highlighting their substantial promise as a novel class of therapeutic tools for a range of illnesses.