Enhanced permeability across Caco-2 cell monolayers by specific mannosylating ligand of buserelin acetate proliposomes

Context: Oral delivery of peptide and protein drugs still remains the area of challenges due to their low stability and permeability across GI tract. Among numerous attempts, the receptor-mediated drug targeting is a promising approach to enhance GI permeability. Objective: The aim of this study was to prepare mannosylated buserelin acetate (MANS-BA) proliposome powders grafted with N-octadecyl-D-mannopyranosylamine (SAMAN) as targeting moiety and evaluate their permeability across Caco-2 cell monolayers. Materials and methods: The MANS-BA proliposome powders were prepared by coprecipitation method. The targeting moiety SAMAN was synthesized in-house and confirmed by characterization using Fourier transform infrared (FTIR) and differential scanning calorimeter (DSC). Results: The MANS-BA liposomes reconstituted from proliposome powders exhibited the oligolamellar vesicular structure of phospholipid bilayer. Their size, zeta potential and entrapment efficiency were in the ranges of 93.11-218.95 nm, -24.03 to -37.15 mV and 21.12-33.80%, respectively. The permeability of reconstituted MANS-BA liposomes across Caco-2 cell monolayers was significantly enhanced to about 1.2- and 2.2-fold over those of conventional BA liposomes and solution, respectively.Discussion: Increase in dicetylphosphate, cholesterol and SAMAN contents resulted in significant increase in size and zeta potential of reconstituted MAN-BA liposomes. The entrapment efficiency was increased with increasing dicetylphosphate and mannitol contents in liposomes containing cholesterol. Conclusions: The significantly enhanced permeability across Caco-2 cell monolayers of MANS-BA liposomes might be due to the role of mannose receptor on intestinal enterocytes.