Journal
JOURNAL OF CONTROLLED RELEASE
Volume 149, Issue 1, Pages 72-80Publisher
ELSEVIER
DOI: 10.1016/j.jconrel.2010.03.001
Keywords
pH-sensitive liposome; Cytoplasmic delivery; Hyperbranched polymer; Membrane fusion; Dendritic cell
Funding
- Ministry of Health, Labor and Welfare of Japan
- Ministry of Education, Science, Sports, and Culture in Japan
- Japan Society for the Promotion of Science
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Previous reports by the authors described intracellular delivery using liposomes modified with various carboxylated poly(glycidol) derivatives. These linear polymer-modified liposomes exhibited a pH-dependent membrane fusion behavior in cellular acidic compartments. However, the effect of the backbone structure on membrane fusion activity remains unknown. Therefore, this study specifically investigated the backbone structure to obtain pH-sensitive polymers with much higher fusogenic activity and to reveal the effect of the polymer backbone structure on the interaction with the membrane. Hyperbranched poly(glycidol) (HPG) derivatives were prepared as a new type of pH-sensitive polymer and used for the modification of liposomes. The resultant HPG derivatives exhibited high hydrophobicity and intensive interaction with the membrane concomitantly with the increasing degree of polymerization (DP). Furthermore, HPG derivatives showed a stronger interaction with the membrane than the linear polymers show. Liposomes modified with HPG derivatives of high DP delivered contents into the cytosol of DC2.4 cells, a dendritic cell line, more effectively than the linear polymer-modified liposomes do. Results show that the backbone structure of pH-sensitive polymers affected their pH-sensitivity and interaction with liposomal and cellular membranes. (C) 2010 Elsevier B.V. All rights reserved.
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