Design, development and evaluation of mannosylated oral Amphotericin B nanoparticles for anti-leishmanial therapy: Oral kinetics and macrophage uptake studies

Abstract

BackgroundThe aim of the present research was to develop Mannosylated Amphotericin B nanoparticles (AmB-BSA-MAN NPs) for targeting M-cells in Peyers patch to enhance drug transport across the intestinal epithelial barrier. MethodsBovine serum albumin (BSA) stabilized AmB NPs were prepared using liquid anti-solvent (LAS) precipitation technique, and different in process parameters were optimized using I-Optimal Response Surface Methodology. Lyophilized AmB-BSA NPs were crosslinked with mannose (MAN) via carbodiimide method using 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDAC). ResultsPrepared NPs were characterized using FT-IR, DSC, XRD, 1H NMR, SEM, and further evaluated for in vitro drug release, macrophage uptake and oral pharmacokinetics studies. FT-IR and 1H NMR results confirmed the compatibility as well as surface grafting of MAN. XRD studies outcomes revealed decreased crystallinity of AmB in the formulation. Fabricated AmB-BSA-MAN NPs were found to be irregular in shape; as confirmed by SEM. The particle size was found to be 303 nm and 352 nm for developed AmB-BSA NPs and AmB-BSA-MAN NPs, respectively. Further, the prepared NPs exhibited superior aqueous solubility and drug release when compared to its pure form. Further, in vitro macrophage uptake of AmB-BSA-MAN NPs in differentiated THP-1 cells was superior to AmB-BSA NPs and AmBisome®, but lesser than Fungizone®. The relative bioavailability of AmB from the prepared AmB-BSA-MAN NPs was found to be 793.2%; fairly higher in contrast to that from the plain AmB. ConclusionOur findings highlight the scope on developing new-fangled oral delivery system for passively targeting M-cells in Peyers patch for more competent and facilitated anti-leishmanial therapy.