Transport mechanism of hydroxy-propyl-beta-cyclodextrin modified solid lipid nanoparticles across human epithelial cells for the oral absorption of antileishmanial drugs

Abstract

BackgroundIn this study, the transport mechanism of fluorescently labeled hydroxypropyl beta-cyclodextrin (HPβ-CD) modified SLNs loaded with Amphotericin B (AmB) and Paromomycin (PM) have been investigated by using in vitro human epithelial cell model of a human colonic adenocarcinoma cell line (Caco-2). MethodsFabrication of HPβ-CD modified fluorescently labeled AmB and PM-loaded SLNs (HPꞵ-CD-FITC-DDSLNs) was performed by using the emulsion solvent evaporation method. Caco-2 cells were used to investigate different endocytosis and exocytosis pathways to be followed by the nanoparticles. Intracellular co-localization of nanoformulation with different organelles was investigated. ResultsThe toxicity studies have shown the biocompatible nature of the modified lipid nanoparticles. The average particle size and PDI of HPꞵ-CD-FITC-DDSLNs were found to be 187 ± 2.3 nm and 0.31 respectively. The most prevalent endocytosis mechanisms were shown to be macropinocytosis and caveolae (lipid raft) dependent pathways. The Golgi complex and endoplasmic reticulum are the confirmed destinations of HPꞵ-CD-FITC-DDSLNs in the Caco-2 cell monolayer, even though lysosomes have been shown to escape and play a minimal role during nanoparticle transport. ConclusionHPꞵ-CD-DDSLNs were found to be biocompatible and safe for delivering hydrophobic as well as hydrophilic drugs through an oral route to target the RES system for the treatment of visceral leishmania. General significanceUnderstanding the process underlying the transport of modified solid lipid nanoparticles for oral drug delivery could be useful for many medicines with low solubility, permeability, and stability.