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- Title
Surface modification of liposomes using polymer-wheat germ agglutinin conjugates to improve the absorption of peptide drugs by pulmonary administration.
- Authors
Murata, Mitsutaka; Yonamine, Takashi; Tanaka, Shota; Tahara, Kohei; Tozuka, Yuichi; Takeuchi, Hirofumi
- Abstract
In this study, we investigated the feasibility of a system based on liposomal surface modification with a novel mucoadhesive polymer-lectin 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 CP-WGA surface-modified liposomes in vivo and in vitro. In association studies, CP-WGA 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 liposome-cell 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 CP-WGA-modified liposomes. Hence, surface modification of liposomes with CP-WGA has potential for effective pulmonary administration of peptides.
- Publication
Journal of pharmaceutical sciences, 2013, Vol 102, Issue 4, p1281
- ISSN
1520-6017
- Publication type
Journal Article
- DOI
10.1002/jps.23463