Disease-Adaptive Drug Delivery to the Inflamed Intestinal Mucosa Using Poly(Lactic-Co-Glycolic Acid)-cyclodextrin Hybrid Nanocarriers

Abstract

Fluctuating severity of symptoms is a common hallmark of many inflammatory disorders, including inflammatory bowel disease (IBD). Addressing the pH changes during active and resting phases in IBD-affected tissue, a disease-adaptive nanocarrier system is designed for oral administration, enabling pH-dependent local drug release. The hybrid carrier combines poly(lactic-co-glycolic acid) and an amphiphilic cyclodextrin derivative, with physicochemical properties and drug release kinetics controlled by adjusting polymer ratios. The systems exhibited baseline drug release at pH 5 with increased rates at pH 2, which is characteristic of actively inflamed IBD tissue. Assessing the impact of biomolecule adhesion, biocorona formation was studied using ex vivo human intestinal fluids. Corona composition highly depended on the patient's prandial state and the nanocarrier matrix, with proteins predominating in the fasted state and lipids in the fed state. Notably, differences in the attachment of proteins and free fatty acids are detected in the latter. Transport studies using human in vitro models of the inflamed intestine revealed mucosal accumulation, facilitating localized drug delivery and effectively reducing cytokine levels to basal concentrations. This hybrid system highlights the potential of disease-adaptive drug release for inflammatory disease treatment and underscores the impact of biocorona formation on therapeutic performance in the gastrointestinal tract.