Etoposide-loaded biodegradable amphiphilic methoxy (poly ethylene glycol) and poly (epsilon caprolactone) copolymeric micelles as drug delivery vehicle for cancer therapy

Abstract

Amphiphilic diblock copolymers composed of methoxy poly ethylene glycol (MePEG) and poly epsilon caprolactone (PCL) were synthesized for the formation of micelles by ring opening mechanism using stannous octoate as a catalyst. The effects of the molecular weight of MePEG and the copolymer ratio on the properties of micelles were investigated by Nuclear Magnetic Resonance (1H-NMR), Fourier Transform Infrared Spectroscopy (FT-IR), and Gel Permeation Chromatography (GPC). The diblock copolymers were self-assembled to form micelles and their hydrophobic core was used for the encapsulation of the anti-cancer drug (etoposide) in aqueous solution. The sizes of micelles were less than 250 nm with a narrow size distribution with monodispersed unimodal pattern. Differential Scanning Calorimetric (DSC) thermogram was done for etoposide-loaded micelles to understand the crystalline nature of the drug after entrapment. A drug loading capacity up to 60% (w/w) with an entrapment efficiency of 68% was achieved as determined by reverse phase high performance liquid chromatography (RP-HPLC). In vitro release kinetics showed a biphasic release pattern of etoposide for 2 weeks. The cytotoxic efficacy of the etoposide-loaded micelles demonstrated greater anti-proliferative activity (IC50 = 1.1 µg/ml) as compared to native drug (IC50 = 6.3 µg/ml) in pancreatic cancer cell line MIA-PaCa-2. Thus, etoposide-loaded MePEG/PCL block copolymeric micelles can be used as an efficient drug delivery vehicle for pancreatic cancer therapy.