Effect of polymer degradation on prolonged release of paclitaxel from filomicelles of polylactide/poly(ethylene glycol) block copolymers.

Paclitaxel is one of the most efficient anticancer agents, but the conventional dosage formulations cause many side effects. PLA-PEG filomicelles are promising carriers of paclitaxel because high loading capacity and long term release can be achieved. Slow release of cytostatic drugs is very advantageous due to prolonged exposure of tumor cells to cytostatic over multiple cell cycles. The aim of this study was to evaluate the potential of bioresorbable PLA-PEG filomicelles for prolonged delivery of paclitaxel. Paclitaxel is encapsulated in PLLA-PEG filomicelles and PDLLA-PEG spherical micelles. Drug release was studied in PBS at 37°C at various pH values to elucidate the influence of polymer degradation on drug release. NMR, GPC and HPLC were used to follow polymer degradation and drug release. The release of paclitaxel is strongly dependent on the degradation of micelles. A biphasic drug release profile is observed for both PLLA-PEG and PDLLA-PEG micelles: slow release in the first phase and faster release in the second phase. Degradation is faster at acidic pH than at pH7.4, and PLLA-PEG filomicelles degrade less rapidly than PDLLA-PEG spherical micelles, leading to various rates of drug release. The correlation between degradation and drug release is very helpful for the development of novel drug carriers with tailored properties. Importantly, the cytotoxic activity of PLLA-PEG filomicelles was evidenced, thus showing their potential as carrier of antitumor drugs.