PREPARATION OF pH-SENSITIVE CORE-SHELL TYPE POLYMERIC MICELLE FROM POLY(PEPTIDE-b-LACTIDE) DIBLOCK COPLYMERS AS BIODEGRADABLE MIOMEDICAL MATERIAL

The formation of polymeric micelles by the self-association of diblock copolymers consisting of hydrophilic and hydrophobic segments in aqueous medium is currently a topic of great interest. This interest is motivated by the attractive applications of polymeric micelles to various research areas such as drug delivery carrier technology and nanotechnology. In the biomedical materials field, polymeric micelles must possess several specific properties to be of use. These include biocompatibility, biodegradability, target specificity, and stability in the body. Polylactide (PLA) is one of the most commonly used relatively hydrophobic and biodegradable polyesters that possess some of the above qualities. A number of polymeric micelles formed from PLA-based amphiphilic diblock copolymers have been investigated in terms of various biomedical applications. Poly(ethylene glycol) (PEG) is frequently chosen as a hydrophilic segment to complement PLA because of its biocompatibility. Kataoka et al. reported the formation of PEG-b-PLA diblock copolymer micelles with modified PEG chains and the application of this micelle as a drug carrier for active targeting. They successfully modified the outer PEG layer of the micelles using an aldehyde group introduced at the PEG terminal. Polypeptides consisting of α-amino acids are synthetically intriguing as polymeric micelles due to their biodegradability and variation in functionality that results from the differences in side chain groups. Previously, we synthesized poly(aspartic acid)-block-polylactide (PAsp-b-PLA) diblock copolymer consisting of a hydrophilic/anionic PAsp segment and a hydrophobic PLA segment, and observed polymeric micelle formation in aqueous solution using a dialysis method. In this study, details regarding the formation of these polymeric micelles are reported. It is well known that the shape and size of polymeric micelles are affected by the ratio of the length of the hydrophilic and hydrophobic segments. To establish the relationship between this factor and polymeric micelle formation in this study, several kinds of PAsp-b-PLA copolymers having various hydrophilic/hydrophobic chain length ratios were synthesized. In addition, the sensitivity of the carboxylic acid groups of the PAsp segment to changes in the pH and the resulting effects on the PAsp-b-PLA polymeric micelles in aqueous solution were observed.