Keywords

polymeric micelles, hydrophobic drugs, cavitation

Abstract

Our research in ultrasonic activated drug delivery motivated us to develop polymeric micelles that sequester hydrophobic drugs (Fig. 1) until they are sheared open by cavitation events produced by low frequency ultrasound (Fig. 2). [1] Using this type of drug delivery system, micelles sequestering drug can circulate freely without releasing their drug until they flow through a tumor or other tissue insonated by low frequency ultrasound. There they release part of their drug (Fig. 3). [2,3] This drug delivery technology was used to reduce tumors in a rat model [4] using block copolymers of PEO and PPO. However, we are always seeking better drug-carrying micelles. This research investigated the polymerization rate kinetics for the production of block copolymers of polyethylene oxide (PEO) and poly(N-isopropylacrylamide) (NIPAAm) that form thermally-reversible self-assembled micelles. Such micelles can be used for ultrasonic-activated drug delivery.The unique polymerization kinetics involves using cerium in the +4 oxidation state, Ce4+. The cerium extracts a hydrogen atom from the end of the PEO chains (Scheme 1), which subsequently initiates free radical polymerization. Although this polymerization has been described qualitatively in the literature [5], there are no reports of the polymerization kinetics, which are needed to control the molecular weight of the resulting block copolymers. We also studied the assembly of these block copolymers into micelles. Some micelles were further stabilized by copolymerizing with a biodegradable crosslinker N,N-bis(acryloyl)cystamine (BAC).

Original Publication Citation

Pitt, W.G. and Zeng, Y., "Polymerization Kinetics of PEO-pNIPAAm Block Copolymers", Trans. Soc. for Biomaterials, 31, 283, Pittsburg, PA, April 26-29, 26