Preparation of a PLA-PEG block copolymer using a PLA derivative with a formyl terminal group and its application to nanoparticulate formulation.
A novel poly(DL-lactic acid) (PLA) derivative with a diethoxy propanol ester at the end, named PLA-acetal, was synthesized by ring opening polymerization using DL-lactide and 3,3-diethoxy propanol. PLA-acetal was hydrolyzed to a PLA derivative with a formyl group, named PLA-aldehyde, by acid treatment. Reductive amination between PLA-aldehyde and methoxypolyethylene glycol amine (MeO-PEG(N)) gave the block copolymer (PLA-(MeO-PEG(N))). Nanoparticles were prepared by emulsification-solvent evaporation or solvent diffusion using PLA-(MeO-PEG(N)) or a conventional methoxypolyethylene glycol-PLA block copolymer, PLA-(MeO-PEG(O)). PLA-(MeO-PEG(N)) nanoparticles had a particle size of 60-340 nm, dependent on the preparative procedure, while PLA-(MeO-PEG(O)) nanoparticles prepared by solvent diffusion showed a particle size of 60 nm. The PLA-(MeO-PEG) nanoparticles with a smaller PEG introduction degree exhibited a more negative zeta potential. 1,1'-Dioctadecyl-3,3,3',3'-tetramethylindodicarbocyanine perchlorate (DiD) could be incorporated efficiently in PLA-(MeO-PEG(N)) nanoparticles. It is suggested that PLA-aldehyde should be useful as a functional intermediate for derivatization of PLA, and PLA-(MeO-PEG(N)) can be used for the preparation of PEG-coated PLA nanoparticles.
Sasatsu
Masanaho
M
Department of Drug Delivery Research, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 142-8501, Japan.
Onishi
Hiraku
H
Machida
Yoshiharu
Y
D002626:Chemistry, Pharmaceutical; D007773:Lactates / Q000138:chemical synthesis*; D049329:Nanostructures / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000138:chemical synthesis*
D007773:Lactates; C088513:poly(lactic acid-ethylene glycol); D011092:Polyethylene Glycols