Preparation and characterization of poly(3‐hydroxybutyrate‐co‐3‐hydroxyvalerate) microspheres for the sustained release of 5‐fluorouracil

Abstract

Biodegradable microspheres were prepared with poly(3‐hydroxybutyrate‐co‐3‐hydroxyvalerate) (PHBV, 85:15 by mole ratio of hydroxybutyrate to hydroxyvalerate) by an water‐in‐oil‐in‐water (W/O/W), oil‐in‐water (O/W) and oil‐in‐oil (O/O) solvent evaporation method for the sustained release of anti‐cancer drug, 5‐fluorouracil (5‐FU) with controlling the fabrication conditions. The shape of microspheres prepared was relatively rough due to highly crystalline property of PHBV and spherical. The efficiency of 5‐FU loading into the PHBV microsphere with O/O method was over 80% compared to that 7% for microspheres by O/W method and below 1% for microspheres by a conventional W/O/W method. However, the most desirable release pattern can be achieved from the O/W method due to the cosolvent effect. The effects of preparation conditions such as the type and amount of surfactant, initial amount of loaded drug, the temperature of solvent evaporation, and etc. on the morphology for W/O/W method were investigated. Possible mechanisms of the desirable sustained release pattern for O/W system have been proposed.