Investigations of pectin nanostructures for enhanced percutaneous delivery of fusidic acid

Abstract

AbstractThe study aims to formulate and characterize nanoformulations produced from amphipathically‐modified pectin containing fusidic acid, making clear the importance of nanocarrier amphipathicity in boosting drug permeation through the skin. For this purpose, the amphipathically‐modified pectin (GBE‐PEC) fabrication was achieved following glycidol butyl ether modification via the nucleophilic substitution SN2 reaction, which was then characterized using thermal analysis, spectroscopic, and chromatographic tools. The materials were subsequently converted into spherical nanostructures (NSs) (size 250–290 nm; zeta potential −25 to −34 mV) via a nanoprecipitation in situ cross‐linking approach, demonstrating low viscosity and good colloidal stability under pH 4 conditions. The encapsulated fusidic acid (loading degree 14.9%) was released from GBE‐PEC NSs in a more controlled fashion, with release profiles best characterized by the Higuchi model. Interactions with HaCaT cells in vitro demonstrated no apparent cytotoxicity at application relevant conditions, with efficient cellular absorption as evidenced by flow cytometry analysis. Using Franz diffusion cells, GBE‐PEC NSs had a 2‐fold greater penetration rate through the Strat‐M® membrane than the native pectin NSs. Overall, the study has introduced new insights into the design, fabrication, characterization, and tremendous potential of NSs formulated from GBE‐PEC for percutaneous delivery of poorly penetrating actives, which merit further analysis.