POLY(2-OXAZOLINE) MICELLAR FORMULATION FOR CANCER THERAPY Public Deposited

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  • March 22, 2019
Creator
  • Wan, Xiaomeng
    • Affiliation: Eshelman School of Pharmacy, Pharmaceutical Sciences Program
Abstract
  • Most nanoparticles have a fairly low threshold for incorporation of such drugs. Previously, we have reported a nanosized polymeric micelles (PM) formulation based on highly defined amphiphilic triblock copolymers of poly(2-oxazoline)s (POx), poly(2-methyl-2-oxazoline-block-2-butyl-2-oxazoline-block-2-methyl-2-oxazoline) (P(MeOx-b-BuOx-b-MeOx)), that have greatly enhanced the solubility of single and multiple drug combinations. In particular, the POx-based PM of paclitaxel (PTX) with unprecedentedly high drug loading of nearly 45 % wt. and controllable ~30 to 40 nm size displayed reduced toxicity and superior efficacy in early and late stage breast cancer models compared to clinically approved Taxol and Abraxane. The co-delivery of drugs in a single nanofomulation remains a principal challenge since poor solubility and differential pharmacokinetics (PK) severely restricts the selection of drugs that can be translated into successful combination treatments. Critical to success is optimizing the relative doses of the drugs to obtain synergistic effects on tumors [4]. Here, we propose that co-loading of PTX and hydrophobic cisplatin prodrug at synergistic drugs ratios in the POx-based drug delivery platform significantly improve the PK profile and efficacy in both ovarian and breast cancer. We also propose that co-loading of etoposide (ETO) and platinate at synergistic drugs ratios in the POx-based drug delivery platform with “worm-like” shape micelles can safely and efficiently treat both SCLC and NSCLC lung cancer. In summary, tri-block POx copolymer is a viable and promising platform for various chemotherapeutic agents, singly and multiply, delivery in cancer therapy.
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Advisor
  • Huang, Leaf
  • Zamboni, William
  • Anders, Carey
  • Kabanov, Alexander
  • Batrakova, Elena
Degree
  • Doctor of Philosophy
Degree granting institution
  • University of North Carolina at Chapel Hill Graduate School
Graduation year
  • 2018
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