Stimuli-responsive chitosan hydrogels for localized anti-inflammatory and wound healing therapies
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This research focuses on the design and development of injectable, stimuli-responsive chitosan hydrogels as smart delivery platforms for both synthetic anti-inflammatory drugs and natural plant extracts. The work builds on thermosensitive chitosan/β-glycerophosphate (CS/GP) systems, whose sol–gel transition at physiological temperature enables in situ gelation at the target site, and adapts this chemistry into a tunable carrier for localized, sustained therapy in infected, inflamed, or otherwise inaccessible regions.
A defining feature of the research is the systematic examination of how loading strategy, polymer composition, and environmental stimuli jointly govern release behavior. Parallel investigations of post-loading and in situ encapsulation demonstrate that a single chitosan platform can be tuned to deliver diclofenac sodium across a broad therapeutic window - from rapid burst release within five hours for acute pain relief to prolonged release over seven days for chronic inflammation management. This direct comparison provides a clear design rationale for matching release kinetics to clinical need without altering the underlying polymer chemistry.
The platform is further extended to natural phytochemicals, addressing the long-standing challenge of poor bioavailability and rapid metabolic degradation that limits the clinical utility of plant-derived bioactives. Antibacterial and anti-inflammatory ethanolic extracts derived from botanical plants, e.g. Triphasia trifolia (limeberry) and Piper betle (betel leaf), were successfully encapsulated in the thermosensitive chitosan-based hydrogels via an in situ loading strategy. The resulting systems exhibited dual pH and temperature responsiveness, controlled release governed by Fickian or quasi-Fickian diffusion mechanisms, biodegradation under simulated physiological conditions, and retained inherent bioactivities of the plant extracts. This line of work bridges traditional herbal medicine and modern controlled-release engineering, supporting plant extracts as quantifiable, well-characterized cargoes in smart material design.
To address the mechanical fragility that limits the practical injectability of pure chitosan hydrogels, a composite system reinforced with polyvinyl alcohol (PVA) was developed. The composite hydrogels retained full thermo-sensitivity, swelling capacity, and pH- and temperature-responsive release while achieving a soft-tissue-mimetic elastic modulus for injection into inflamed regions. This iterative process of identifying structural limitations and resolving them through rational composite design, without compromising functional performance, reflects a coherent materials engineering progression across the research program.
Building on this foundation, the research extends to topical delivery through a crosslinker-free PVA/CS hydrogel patch formed via repeated freeze-thaw cycling. pH-sensitivity of chitosan governs BLE release, as acidic wound conditions trigger network expansion and a rapid burst of betel leaf extract for immediate antibacterial and anti-inflammatory action, followed by sustained release as the wound heals toward neutral pH. Tuning polymer composition, freeze-thaw cycles, and extract loading allows the resulting hydrogel to achieve both high gel fraction and swelling capacity as well as wound-conformable mechanical strength, reinforcing the research's central theme of engineering stimuli-responsive carriers that deliver natural bioactives effectively.
The unifying direction of this research is to build a versatile and modular hydrogel platform in which the release window can be tailored from hours to days, responsiveness can be layered across temperature, pH, and enzymatic triggers, and the cargo scope can extend across both pharmaceutical and phytochemical agents. This direction aims to provide a reproducible design framework for smart, functional biomaterials that respond to the physiological cues of the wound microenvironment, supporting the continued advancement of therapeutic systems for localized inflammation and wound healing.
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