Reverse polymeric micelles for pharmaceutical applications.
writer：M.-C. Jones, H. Gao, J.-C. Leroux,
keywords：poly(glycidyl methacrylate)s, star-shaped polymers, reverse micelles, water-free formulation, peptide
source：期刊
specific source：J. Controlled release , 2008;132:208-215.
Issue time：2008年
Star-shaped (4- to 8-arms) and linear poly(glycidyl methacrylate)s were synthesized by atom transfer radical polymerization as precursors of poly(glycerol methacrylate)s (PGOHMAs). The water-soluble PGOHMA backbones were modified through the esterification of pendant hydroxyl functions with acyl chlorides (12 to 18 carbons). Alkyated PGOHMAs were shown to self-assemble into reverse micelles (RMs) in organic solvents and/or oil. The resulting nanosized aggregates (20–60 nm) were able to reversibly extract anionic dyes from water and solubilise them in an organic phase. Furthermore, the encapsulation of vasopressin, a model peptide, in RMs significantly improved its solubility in an oily vehicle. This observation led to the
development of water-free peptide formulations. In vitro release studies showed that the entrapped peptide slowly diffused out of an oily RM solution (b15% in 7 days). The release rate could be significantly increased upon emulsification of the oleaginous phase. In vivo, the subcutaneous administration of loaded RMs to rats
significantly prolonged the pharmacological effect of vasopressin (N48 h vs. 8–10 h for an aqueous solution). These results highlight the ability of RMs to act as solubilizers for hydrophilic solutes in organic media, a property that may be exploited for applications in organic chemistry and pharmaceutical technology.