Biodegradable, Drug-Loaded Nanovectors via Direct Hydration as a New Platform for Cancer Therapeutics

Roxane Ridolfo, Benjamin C. Ede, Paraskevi Diamanti, Paul B. White, Adam W. Perriman, Jan C.M. van Hest*, Allison Blair, David S Williams

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)

7 Citations (Scopus)
257 Downloads (Pure)

Abstract

The stabilization and transport of low-solubility drugs, by encapsulation in nanoscopic delivery vectors (nanovectors), is a key paradigm in nanomedicine. However, the problems of carrier toxicity, specificity, and producibility create a bottleneck in the development of new nanomedical technologies. Copolymeric nanoparticles are an excellent platform for nanovector engineering due to their structural versatility; however, conventional fabrication processes rely upon harmful chemicals that necessitate purification. In engineering a more robust (copolymeric) nanovector platform, it is necessary to reconsider the entire process from copolymer synthesis through self-assembly and functionalization. To this end, a process is developed whereby biodegradable copolymers of poly(ethylene glycol)-block-poly(trimethylene carbonate), synthesized via organocatalyzed ring-opening polymerization, undergo assembly into highly uniform, drug-loaded micelles without the use of harmful solvents or the need for purification. The direct hydration methodology, employing oligo(ethylene glycol) as a nontoxic dispersant, facilitates rapid preparation of pristine, drug-loaded nanovectors that require no further processing. This method is robust, fast, and scalable. Utilizing parthenolide, an exciting candidate for treatment of acute lymphoblastic leukemia (ALL), discrete nanovectors are generated that show strikingly low carrier toxicity and high levels of specific therapeutic efficacy against primary ALL cells (as compared to normal hematopoietic cells).

Original languageEnglish
Article number1703774
Number of pages10
JournalSmall
Volume14
Issue number32
Early online date12 Jul 2018
DOIs
Publication statusPublished - 9 Aug 2018

Keywords

  • acute leukemia
  • drug delivery
  • nanomedicine
  • parthenolide
  • self-assembly

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