Lipids as naturally occurring biomolecules have broad application in pharmaceutical industry. However, few attempts have been made in terms of their applications as amphiphilic block copolymers for drug delivery. In this work, a biodegradable micellar drug delivery system with a temperature-sensitive poly(N-vinylcaprolactam) shell and renewable fatty acid based polymer core was developed. A series of well-defined amphiphilic block copolymers poly(vinyl stearate)/ poly(vinyl laurate)-b-poly(N-vinylcaprolactam) (PVS/PVL-b-PNVCL) were synthesized via reversible addition fragmentation chain transfer (RAFT) polymerization under microwave irradiations in 28 min. The PVS/PVL content of the hydrophobic segment was systematically varied to explore their influence on physicochemical properties and in vitro biological performance. In aqueous media, these block copolymer micelles exhibited worm-like or spherical morphology with monodispersed size distributions of 70-140 nm and low critical micelle concentrations (CMCs) of 0.001-0.003 mg/mL. Nile Red and a hydrophobic anticancer model drug doxorubicin (DOX) were incorporated into the micelles to investigate the micellar serum stability and drug encapsulation ability. DOX-loaded micelles with a drug loading of 10.4 wt% showed temperature-triggered DOX release in simulated physiological temperature compared to ambient temperature (25 ^oC). At 37 ^oC, a sustained drug release rate was observed with ~80% release of drug within 72 h. In vitro cytotoxicity studies demonstrated that the blank block copolymer micelles are biocompatible with different cell lines, while DOX-loaded micelles showed a good anticancer efficacy against Hela cells. Cellular uptake study showed that DOX-loaded copolymer micelles were rapidly internalized by the cells. These results suggest the opportunity to further explore the utilization of renewable materials as replacements of synthetic materials for smart drug delivery nanoplatforms.

Huiqi Wang

PhD candidate, University of Alberta

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