Docetaxel-Loaded Mixed Micelles and Polymersomes Composed of Poly (caprolactone)-Poly (ethylene glycol) (PEG-PCL) and Poly (lactic acid)-Poly (ethylene glycol) (PEG-PLA): Preparation and In-Vitro Characterization

Document Type: Research article

Authors

1 Targeted Drug Delivery Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.

2 Department of Pharmacolgy, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.

3 Targeted Drug Delivery Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, , Iran.

4 Pharmaceutical Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.

5 Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.

Abstract

Microwave irradiation was used to synthesize PEG-PCL and PEG-PLA copolymers that are composed of biodegradable polymers including PEG, PLA, and PCL. These copolymers were used for loading docetaxel in nanoparticles. Single emulsion-solvent evaporation technique was applied for preparing the PEG-PLA and PEG-PCL mixed nanoparticles (micelles and polymersomes) with different proportions, including 0:1, 1:1, 3:1, 1:3, and 1:0. The unimodal gel permeation chromatography curve showed low polydispersity of the di-block copolymers. The in vitro drug release curves of formulations were compared. Micelles and polymersomes of 75% PEG-PCL and 25% PEG-PLA (P5 and M5) have the lowest burst release (5%) at the same period compared to other copolymers. The dynamic light scattering and TEM results clarified that the size and shape of the formulations are uniform. The cytotoxicity effect of P5 and M5 was evaluated in different cell lines. The best one was found to P5 with IC50 between 1.48-11.79 g/ml. The pro-apoptotic effect of P5 was confirmed with flow cytometry study. These mixed micelles (M5) and polymersomes (P5) was found to be superior formulations than non-mixed ones.

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