Enhanced intestinal permeation of novel sulpiride electrospun nanofibers: formulation, optimization, and ex vivo evaluation of drug absorption.

Abstract

Significance: Electrospinning presents a promising avenue for drug delivery applications by integrating traditional solid dispersion methods with nano-medicinal strategies. Electrospun nanofibers (NFs) can be tailored to control the composition, diameter, and orientation of the NFs based on the intended application.

Objectives: Herein, we aim to fabricate novel polymeric NFs loaded with sulpiride (SUL) utilizing Eudragit L100-55 (EL100-55) polymers to improve the dissolution and permeability of a model class IV drug.

Methods: Various factors were assessed to optimize the electrospun NF formulation, including polymer concentrations, flow rate, and drug amount.

Results: The electrospinning process yielded defect-free SUL-loaded EL100-55 NFs. The physicochemical analysis demonstrated favorable attributes in all formulations, encompassing high drug loading, encapsulation efficiency, and rapid drug release. Nanofiber formulations exhibited superior dissolution due to their extensive surface area. Modified non-everted sac experiments revealed a twofold increase in SUL permeation through the intestinal membrane upon EL100-55 encapsulation, emphasizing its impact on tight junction modulation in both NF and solid dispersion formulations. Enhanced drug permeation in the NF formulation involved dual mechanisms: transcellular diffusion and widening of the paracellular pathway. In contrast, the solid dispersion formulation prepared via solvent evaporation predominantly widened the paracellular pathway. Visualization techniques illustrated the NFs' robust affinity for the transcellular pathway.

Conclusion: Sulpiride encapsulation into EL100-55-NF is a promising solution for BCS class IV drugs facing solubility and permeability challenges.