NSTI Nanotech 2009

Dendrigraft Polycaprolactone Unimolecular Micelles with High Paclitaxel-Loading Capacity

Z.L. Zhong, X.J. Ling, F.J. Chen, R.X. Zhuo
Wuhan University, CN

Keywords: dendrigraft polymer, polycaprolactone, amphiphilic, unimolecular micelle, polymeric nanoparticle, PTX


Paclitaxel (PTX) is one of the most effective and widely used drugs in cancer chemotherapy. Because of its low solubility in water, standard formulation of PTX requires the use of solvents, such as polyoxyethylated castor oil and dehydrated alcohol, which contribute to most of the toxicity commonly associated with PTX-based therapy. Encapsulation in biodegradable polymeric nanoparticles represents a most promising approach to achieve an organic solvent-free PTX delivery system. We designed a novel amphiphilic PEGlated dendrigraft polycaprolactone (PEG-g-dendr-PCL) for use as drug delivery systems. Due to the dendritic structure, it forms stable unimolecular nano-sized micelles with very high drug-loading capacity. The dendrigraft PCL was prepared by a generation-wise route.PEGlation was achieved by reaction of MePEG-COCl with the pendant hydroxyl groups to give the amphphilic PEG-g-dendr-PCL. The amphiphilic polyesters readily form nanoparticles in water with narrow PDI. TEM images showed the particle size was in good accordance with the molecular weight, revealing formation of unimolecular micelles. The G1 amphiphilic dendrigraft polymer encapsulated PTX efficiently with loading capacity as high as 35% at encapsulation rate of 60%.
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