Surface modification of liposomes using polymerwheat germ agglutinin conjugates to improve the absorption of peptide drugs by pulmonary administration

In this study, we investigated the feasibility of a system based on liposomal surface modification with a novel mucoadhesive polymerlectin conjugate for the pulmonary delivery of therapeutic peptides and proteins. We covalently attached wheat germ agglutinin (WGA), a ligand that specifically interacts with alveolar epithelial cells, to carbopol (CP), a mucoadhesive polymer, using the carbodiimide method and then evaluated the efficacy and potential toxicity of CPWGA surface-modified liposomes in vivo and in vitro. In association studies, CPWGA modification enhanced the interaction with A549 lung epithelial cells compared with unmodified or CP-modified liposomes. This increased association was dependent on temperature and the surface concentration of free WGA. These results suggested synergy of WGA and CP, and retention of the biological cell binding activity of WGA, leading to improved liposomecell interactions. Moreover, improvement of liposomal bioadhesion to lung epithelia significantly enhanced and prolonged the therapeutic efficacy of calcitonin, a model peptide drug, without any evidence of toxicity, following administration of calcitonin-loaded CPWGA-modified liposomes. Hence, surface modification of liposomes with CPWGA has potential for effective pulmonary administration of peptides. (c) 2013 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 102:12811289, 2013