Carboxylated hyperbranched poly(glycidol)s for preparation of pH-sensitive liposomes.
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.
Yuba
Eiji
E
Department of Applied Chemistry, Graduate School of Engineering, Osaka Prefecture University, 1-1 Gakuen-cho, Naka-ku, Sakai, Osaka 599-8531, Japan.
Harada
Atsushi
A
Sakanishi
Yuichi
Y
Kono
Kenji
K
D000818:Animals; D001190:Arylsulfonates / Q000008:administration & dosage / Q000737:chemistry; D002460:Cell Line; D002626:Chemistry, Pharmaceutical; D003593:Cytoplasm / Q000378:metabolism; D004337:Drug Carriers / Q000138:chemical synthesis* / Q000737:chemistry; D005434:Flow Cytometry; D016650:Fluorescein-5-isothiocyanate / Q000008:administration & dosage / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D057927:Hydrophobic and Hydrophilic Interactions; D008081:Liposomes; D015093:Meglutol / Q000031:analogs & derivatives* / Q000737:chemistry; D008561:Membrane Fusion; D051379:Mice; D018613:Microscopy, Confocal; D015394:Molecular Structure; D008970:Molecular Weight; D010047:Ovalbumin / Q000008:administration & dosage / Q000737:chemistry; D010316:Particle Size; D011409:Propylene Glycols / Q000138:chemical synthesis* / Q000737:chemistry; D012995:Solubility
D001190:Arylsulfonates; D004337:Drug Carriers; D008081:Liposomes; D011409:Propylene Glycols; C502907:polyglycidol; C033686:3-methylglutaric acid; D010047:Ovalbumin; D015093:Meglutol; D016650:Fluorescein-5-isothiocyanate; C005047:pyranine