Dual-Triggered PLGA Microspheres of Dapagliflozin: Ph + Enzyme Responsive for Colon-Targeted Delivery in IBD + Type 2 Diabetes Mellitus Patients

Abstract

Inflammatory bowel disease (IBD) and type 2 diabetes mellitus (T2DM) are chronic disorders that may coexist, making long-term oral drug therapy challenging because of altered gastrointestinal physiology and reduced drug bioavailability. Dapagliflozin, a sodium-glucose cotransporter-2 (SGLT2) inhibitor, has demonstrated antihyperglycemic and anti-inflammatory potential; however, conventional oral formulations release the drug in the upper gastrointestinal tract, which may limit its therapeutic effectiveness in patients with intestinal inflammation. The present study proposes the development of dual-triggered poly(lactic-co-glycolic acid) (PLGA) microspheres for colon-targeted delivery of dapagliflozin using a pH- and enzyme-responsive approach. PLGA microspheres are prepared by the solvent evaporation technique and further coated with a pH-sensitive polymer to protect the formulation during gastric transit. Drug release is designed to remain minimal in the stomach and small intestine and to increase in the colonic environment, where alkaline pH and bacterial enzymes promote polymer degradation and drug release. The prepared microspheres are evaluated for particle size, morphology, encapsulation efficiency, drug loading, swelling behavior, in vitro release, enzyme-responsive release, stability, and release kinetics. The dual-triggered system is expected to provide site-specific drug delivery, minimize premature drug release, enhance therapeutic efficacy, reduce systemic adverse effects, and improve patient compliance. This novel colon-targeted PLGA microsphere formulation may represent a promising strategy for managing patients with IBD and coexisting type 2 diabetes mellitus.