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Biodegradable,Drug‐Loaded Nanovectors via Direct Hydration as a New Platform for Cancer Therapeutics
Authors:Roxane Ridolfo  Benjamin C Ede  Paraskevi Diamanti  Paul B White  Adam W Perriman  Jan C M van Hest  Allison Blair  David S Williams
Affiliation:1. Biomedical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands;2. School of Cellular and Molecular Medicine, University of Bristol, Bristol, UK;3. Bristol Institute for Transfusion Sciences, NHS Blood and Transplant, Bristol, UK;4. Institute for Molecules and Materials, Radboud University, Nijmegen, The Netherlands;5. Department of Chemistry, Swansea University, Swansea, UK
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).
Keywords:acute leukemia  drug delivery  nanomedicine  parthenolide  self‐assembly
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