(475w) Preparation of Polysuccinimide Microcapsules with pH-Response of Drug Release

Polysuccinimide (hearafter abbreviated as PSI) is biodegradable polymer, which is prepared by the polycondensation of L-aspartic acid. Hydrolysis of PSI yield poly(aspartic acid) (hearafter abbreviated as PASP), which is water-soluble and biodegradable polymer. Therefore, the dissolution in water of PSI changes by the degree of hydrolysis of PSI and the hydrolysis rate is accelerated in high pH region. To utilize the property of hydrolysis of PSI, we try to prepare the PSI microcapsules enclosing antitumor agent having a pH-response of release. PSI microcapsules enclosing Irinotecan hydrochloride (CPT-11) were prepared by solvent evaporation method via O/O emulsion system. The obtained PSI microcapsules had a smooth surface and spherical, which is approximately 30 μm of diameter. CPT-11 was successfully microencapsulated with high entrapment of above 90 %. We performed in vitro release test in an aqueous media with variety of pH. In pH 5 buffer solution, CPT-11 was released at constant for 1 week with a no initial burst. The release profile of CPT-11 in same pH was equivalent without respect to the amount of CPT-11 enclosing in PSI microcapsules. Therefore, it was considered that CPT-11 was uniformly dispersed in PSI microcapsules, exhibiting a zero-order release with a no initial burst. On the other hand, it was clearly observed the pH-dependency of release rate. That is, the higher pH of aqueous media increased the release rate. This is because of dissolution in aqueous media of PSI microcapsule by hydrolysis of PSI in higher pH. Moreover, the release mechanism of CPT-11 from PSI microcapsules was investigated by observing the diameter and surface/internal structure of PSI microcapsules from SEM images after incubation in aqueous media. The diameter of PSI microcapsules was constant after release and maintained a smooth surface. Surprisingly, it was found that the hole was observed in center of microcapsules. It is considered that the erosion of PSI microcapsule was not occurred from microcapsule surface but from inside of microcapsule.