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

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.

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.

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).

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.

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.

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.