The continued development of a novel drug delivery vehicle for pharmacological treatment of tumors is proposed. The vehicle is a star structured polymer having lipophilic and hydrophilic segments to promote both encapsulation of poorly soluble drugs and solubility of the complex in physiological fluids. In an aqueous environment the star polymer forms a """"""""unimolecular micelle"""""""", which shields the encapsulated drug from the outer environment. The stability of the unimolecular structure will minimize early degradation of the encapsulated drug, decrease harmful side effects from premature drug release, and facilitate site-specific drug targeting to selected tissues. Each micelle will have an identical structure and molecular weight that will promote uniform drug loading levels and a predictable, well-controlled drug release rate.
The specific aims i n the Phase II program are a) to synthesize a range of star polymer structures to develop structure-property relationships, b) to use these structures to develop and optimize the drug encapsulation process for the model anticancer drug etoposide, and, c) by in vitro and in vivo testing at the University of Nebraska Medical Center, determine whether incorporation of anticancer drugs into star polymer micelle enhances therapy of cancer tumors.
| Wang, Fei; Bronich, Tatiana K; Kabanov, Alexander V et al. (2008) Synthesis and characterization of star poly(epsilon-caprolactone)-b-poly(ethylene glycol) and poly(L-lactide)-b-poly(ethylene glycol) copolymers: evaluation as drug delivery carriers. Bioconjug Chem 19:1423-9 |
