Biodegradable, Drug‐Loaded Nanovectors via Direct Hydration as a New Platform for Cancer Therapeutics. Issue 32 (12th July 2018)

• Record Type: Journal Article
• Authors: Ridolfo, Roxane; Ede, Benjamin C.; Diamanti, Paraskevi; White, Paul B.; Perriman, Adam W.; van Hest, Jan C. M.; Blair, Allison; Williams, David S.
• Is Part Of: Small. Volume 14:Issue 32(2018)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2018-07-12
• Subjects: acute leukemia -- drug delivery -- nanomedicine -- parthenolide -- self‐assembly; Nanotechnology -- Periodicals; Nanoparticles -- Periodicals; Microtechnology -- Periodicals; 620.5
• DOI: 10.1002/smll.201703774
• Languages: English
• ISSNs: 1613-6810

Abstract

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). Abstract : Direct hydration of biodegradable copolymers into well‐defined, drug‐loaded nanovectors is a new platform for the development of anticancer therapeutics. Without the use of harmful solvents and no purification process (due to complete drug encapsulation), this system is extremely robust and producible. Application toward Leukemia therapy in vitro highlights the utility and biocompatibility of this system.