A bioinspired, pH-responsive microsphere matrix of cold-water extracted Colocasia esculenta mucilage and alginate: a new approach for sustained oral delivery of tramadol

Abstract

Natural polymers derived from plant mucilages are increasingly explored as release-modifying agents in advanced drug delivery systems. This study presents an innovative approach utilizing cold-water extraction and ethanol precipitation to obtain Colocasia esculenta mucilage (CEM), which was then used to fabricate Tramadol hydrochloride-loaded microspheres via ionic gelation. A three-level, two-factor central composite design was employed to optimize a cross-linked CEM–alginate matrix, using polymer concentrations as independent variables, and particle size and encapsulation efficiency as response parameters. The optimized formulation exhibited stable, spherical microspheres with pH-responsive swelling and degradation behavior, high encapsulation efficiency (90.10%), and an average particle size of 726 μm. Characterization by FTIR, DSC, and XRD confirmed drug–polymer compatibility, while SEM analysis revealed a rough, wrinkled surface with fine pores. In vitro studies demonstrated pH-dependent drug release, achieving 67.30% release over 12 hours. In vivo evaluations in rabbits confirmed the formulation's safety, improved bioavailability, and prolonged gastrointestinal residence time. These results highlight the potential of cold-extracted CEM–alginate microspheres as a biocompatible, pH-responsive platform for sustained oral delivery of Tramadol. Furthermore, the simplicity and reproducibility of the ionic gelation method indicate good potential for formulation scalability, and future studies may explore the applicability of this CEM–alginate platform for other therapeutic agents requiring sustained oral delivery.