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Clickable polyoxetane carrier for drug delivery
Patent Number: US9421276

Executive Summary:
  • Invention Type: Diagnostic/Therapeutic
  • Patent Status: Active (US grant)
  • Patent Link: https://patents.google.com/patent/US9421276/
  • Research Institute: Virginia Commonwealth University
  • Disease Focus: Cancer
  • Lead Challenge Inventor: Hu Yang
  • Inventors: Hu Yang, Olga Zolotarskaya, Kenneth J. Wynne, Kristoffer Valerie 
  • Development Stage: In vitro data in human cancer cells
  • Novelty:
    • High efficiency of camptothecin covalent coupling to polyoxetane carrier
    • Low toxicity and immunogenicity of a polyoxetane carrier
  • Clinical Applications:
    • Drug delivery system to treat cancer
    • Medical imaging for diagnostics

General Description:
Polymeric carriers are an important class of vehicles for delivery of drugs and imaging agents. An ideal carrier should be non-toxic and non-immunogenic and possess a high cargo capacity. In this invention, PEG-grafted polyoxetane brush polymers are characterized as a modular platform for efficient delivery of anticancer drugs. Camptothecin delivery to cancer cells is used as a proof of principle for use of copper (I)-catalyzed azide-alkyne cycloaddition (CuAAC) click chemistry. It demonstrates high coupling efficiency and allows precise control of compositions and functionalization. Application of CuAAC to PEG-based polymers for camptothecin delivery is novel and potentially increases bioavailability and specificity of this popular anti-cancer agent.

Scientific Progress:
Branched polymers and dendrimers carrying CPT were synthesized using similar approaches (refs 2 and 3). In the latter case, a 185-fold increase of cytotoxic activity relative to free CPT (ref. 3).

Future Directions:
  • Pre-clinical studies in vivo

Strengths:
  • Potentially general approach with a variety of drug delivery applications

Weaknesses:
  • Lack of in vivo data

Patent Status:
  • Priority date: 2012-08-31
  • Filing date: 2015-09-17
  • Publication date: 2016-08-23
  • Grant date: 2016-08-23

Publications:
1: Zolotarskaya OY, Wagner AF, Beckta JM, Valerie K, Wynne KJ, Yang H. Synthesis of water-soluble camptothecin-polyoxetane conjugates via click chemistry. Mol Pharm. 2012 Nov 5;9(11):3403-8. doi: 10.1021/mp3005066. Epub 2012 Oct 23. PubMed PMID: 23051100; PubMed Central PMCID: PMC3496795.
 
2: Sharma K, Zolotarskaya OY, Wynne KJ, Yang H. Poly (ethylene glycol)-armed hyperbranched polyoxetanes for anticancer drug delivery. J Bioact Compat Polym. 2012 Nov;27(6):525-539. PubMed PMID: 23226692; PubMed Central PMCID: PMC3513288.
 
3: Zolotarskaya OY, Xu L, Valerie K, Yang H. Click synthesis of a polyamidoamine dendrimer-based camptothecin prodrug. RSC Adv. 2015;5(72):58600-58608. Epub 2015 Jun 29. PubMed PMID: 26640689; PubMed Central PMCID: PMC4669072.
 
Inventor Bio: Hu Yang
http://www.egr.vcu.edu/directory/huyang/
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