Long-term delivery of all-trans-retinoic acid using biodegradable PLLA/PEG-PLLA blended microspheres

All-trans-retinoic acid (atRA) has been proved to be effective against seve ral malignancies in human clinical trials. However, in many patients who we re treated with atRA, the cancer relapsed after a brief remission. One reas on for such relapse is that atRA is metabolized by specific P450s that are induced in the liver during prolonged atRA treatments. In order to overcome such a drawback of atRA, we prepared biodegradable microspheres to provide continuous release of atRA for a long period of time. These biodegradable microspheres were prepared by poly(L-lactide) (PLLA) and polyethylene glyco l (PEG)-PLLA diblock copolymers (PLE) in various blending ratios to control the release rate of atRA. As the PLE content in microsphere was increased, the density of the hydrophilic PEG block of PLE on microsphere surfaces in creased and the microspheres were dispersed well in PBS without any surfact ants. Various release patterns of atRA were obtained according to PLE and a tRA contents in the microspheres. Especially. the pseudo-zero-order release profiles were observed for 5 weeks when the contents of PLE and atRA in th e microspheres were above 4 wt.%. (C) 2001 Elsevier Science B.V. All rights reserved.