Development of an injectable thermosensitive chitosan-based hydrogel for localized rutin delivery optimized using Box-Behnken design.

OBJECTIVE

The objective of the present study was to develop, optimize, and evaluate a chitosan (CS)-based hydrogel incorporating rutin for localized drug-delivery.

SIGNIFICANCE: Rutin, a naturally occurring flavonoid, possesses significant antioxidant, anti-inflammatory, and anticancer properties. However, its therapeutic applications are limited due to poor solubility and low bioavailability. The development of a CS-based injectable hydrogel system offers a promising strategy for enhancing localized delivery, improving drug retention, and achieving release at the target site.

METHODS

Box-Behnken Design (BBD) was employed for optimization, where CS concentration (A) and β-Gly concentration (B) were selected as critical material attributes (CMAs), and stirring speed (C) was selected as a critical process parameter (CPP). The hydrogel formulations were evaluated based on parameters including gelation time and swelling ratio. Additionally, rheological properties and in vitro drug-release studies were performed to assess formulation performance.

RESULTS

BBD identified an optimized formulation comprising 1.8% w/v CS, 35% w/v β-Gly, and a stirring speed of 460 rpm, which produced a hydrogel with a gelation time of 148 ± 1.1 s and a swelling ratio of 134.45% ± 1.4%. The experimental responses showed close agreement with the predicted values, confirming the robustness of the optimization model. The optimized hydrogel exhibited shear-thinning behavior suitable for injection and achieved approximately 86% cumulative rutin release over 24 h. Drug-release followed the Korsmeyer-Peppas model, indicating a combined diffusion and polymer relaxation mechanism.

CONCLUSIONS

The QbD-based BBD approach enabled the efficient optimization of an injectable thermosensitive CS-based hydrogel system for localized delivery of rutin. The formulation exhibited desirable physicochemical and rheological properties along with controlled drug-release behavior. This hydrogel system represents a promising approach for enhancing the therapeutic efficacy of rutin in localized treatment applications.