Factorial Design-Based Development and Evaluation of Metformin Hydrochloride-Loaded Mucoadhesive Microspheres for Sustained Anti Hyperglycaemic and Anticancer Activity

Abstract

The present study aimed to develop and optimize Metformin Hydrochloride-loaded mucoadhesive microspheres for sustained anti-hyperglycaemic and anticancer activity using factorial experimental design. Microspheres were prepared by ionotropic gelation employing sodium alginate and chitosan as mucoadhesive polymers. A 3² full factorial design was utilized to evaluate the influence of sodium alginate concentration and calcium chloride concentration on particle size, entrapment efficiency, mucoadhesion, and drug release behaviour. The prepared microspheres were evaluated for physicochemical properties, surface morphology, swelling behaviour, in vitro drug release, release kinetics, anti-hyperglycaemic activity, and anticancer potential against MCF-7 breast cancer cell line. The optimized formulation exhibited high entrapment efficiency (88.7 ± 2.1%), excellent mucoadhesion (93.8 ± 2.6%), and sustained drug release over 12 hours. Release kinetic analysis revealed Higuchi diffusion controlled non-Fickian release behaviour. The optimized microspheres demonstrated enhanced α-amylase and α glucosidase inhibitory activity compared to free drug. In vitro anticancer evaluation showed improved cytotoxic activity with lower IC₅₀ value against MCF-7 cells. Stability studies confirmed acceptable physicochemical stability of the optimized formulation. The developed microsphere system demonstrated promising potential as a sustained oral drug delivery platform for combined anti-hyperglycaemic and anticancer applications.