Biodegradable brush copolymer nanomicelles for smart release of doxorubicin

Background and objective: In cancer therapy, smart and biocompatible nanocarriers are the most important features of therapeutic agents. pH-sensitive drug delivery nanocarriers which can be remotely prompted are attractive for patients management  and therapeutic purposes. In this paper, a novel nanocarrier was fabricated and investigated for controlled release of Doxorubicin (DOX). Materials and methods: Self-assembled nanomicelles containing a hydrophilic core and a hydrophobic shell were successfully prepared using poly(2-hydroxyethyl methacrylate-graft-ε-caprolactone)-block-poly (methacrylic acid) [P(HEMA-g-CL)-b-(PMAAc)] brush copolymer by combining reversible addition-fragmentation chain transfer polymerization (RAFT) and ring open polymerization (ROP). Morphology, micelles properties, and pH-sensitive behavior were studied by field emission scanning electron microscopy (FESEM), transmission electron microscope (TEM) and distribution laser-scattering (DLS) analysis. Results and conclusion: Molecular weight of P(HEMA-g-CL) and [P(HEMA-g-CL)-b-PMAAc] samples was obtained as 15117 g mol-1 and 25887 g mol-1, respectively. The polydispersity index (PDI) of P(HEMA-g-CL) (PDI = 1.14) and [P(HEMA-g-CL)-b-PMAAc] (PDI = 1.19) synthesized byRAFT polymerization were relatively low, suggesting good control of the technique over the process. The self-assembled micelles were pH-sensitive and showed low critical concentration in water. TEM showed that the micelles had nanosized spherical shape with average size of 35 nm. The critical micelle concentration (CMC) value of [P(HEMA-g-CL)-b-PMAAc] micelle was 0.025 g l-1. Encapsulation efficacy of the nanomicelle was 94.3%. Release behavior of DOX from the nanomicelles revealed that rate of core release could be efficiently controlled by body temperature and pH. In this regard, the release rate at pH of 7.4 and 5.4 was 54.73% and 36.52%, respectively. As a conclusion, structure of the nanocarrier and its controllable characteristics introduced it as appropriate vehicle in drug delivery.

Keywords:

Cancer therapy , doxorubicin , Nanomicelle , pH-sensitive