Niosomes for oral drug delivery: factors affecting pharmacokinetics and intestinal transport mechanisms

Oral administration is regarded as the most common and convenient drug delivery route. However, numerous drugs face challenges such as poor solubility, limited permeability, instability, and first-pass metabolism, which hinder intestinal absorption and therefore limit their clinical application. Niosomes, vesicular structures self-assembled from non-ionic surfactants and cholesterol, offer a promising strategy for enhancing oral bioavailability. This review gathers findings from recent studies to examine how key vesicle properties, such as surfactant type and ratio, cholesterol content, particle size, and surface charge, affect the oral pharmacokinetics of drugs (area under plasma concentration-time curve, C_max, and T_max). The effect of surface modification approaches, such as PEGylation and chitosan coating, on enhancing mucosal adhesion, enzymatic resistance, and sustained release has been reviewed. The main mechanisms involved in the ability of niosomes to enhance the oral drug absorption, including enhanced endocytosis, modulation of tight junctions to improve paracellular drug absorption, and elevated lymphatic transport via chylomicron formation and M-cell transcytosis, are also outlined. Characterization of niosomes required for oral administration, including particle size measurement, drug release behavior, stability evaluation in gastrointestinal media, and complementary evaluations such as cytotoxicity and mucoadhesion, is also summarized. Furthermore, we discussed evidence of intact vesicle absorption, safety issues, and regulatory challenges. This review provides a perspective for future research and a deeper understanding of niosomes' in vivo behavior, which could be used as a comprehensive guide to design and optimize oral niosomal formulations.