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).
Highlights
The stabilization and transport of low-solubility drugs, by encapsulation in therapeutic nanovectors there are, a number of issues that cause connanoscopic delivery vectors, is a key paradigm in nanomedicine. tention: (1) the use of harmful substances
Block copolymers comprising varying lengths of PTMC with 1 kDa poly(ethylene glycol) (PEG) (Table S1, Supporting Information) were synthesized utilizing the nontoxic organocatalyst methanesulfonic acid according to literature protocols.[31,32]
Self-assembly of PEG–PTMC copolymers was accomplished by dissolution at 50 wt% in viscous oligo(ethylene glycol) (OEG) (Mw = 350 Da, ρ = 1.09 g mL−1) and subsequent hydration through stirring with buffer
Summary
The stabilization and transport of low-solubility drugs, by encapsulation in therapeutic nanovectors there are, a number of issues that cause connanoscopic delivery vectors (nanovectors), is a key paradigm in nanomedicine. tention: (1) the use of harmful substances. (copolymeric) nanovector platform, it is necessary to reconsider the entire tinent because so many nanomedical 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 formulations fail to reach the clinic due to unforeseen complications.[7] For this reason, structures generated by the selfassembly of amphiphilic block copolymers have received much attention due to their uniform, drug-loaded micelles without the use of harmful solvents or the need excellent versatility and physical properfor purification. The direct hydration methodology, employing oligo(ethylene ties.[8,9,10,11,12,13,14] In particular, the implementation glycol) as a nontoxic dispersant, facilitates rapid preparation of pristine, drugloaded nanovectors that require no further processing This method is robust, fast, and scalable. Introduction rate picture of the size and shape of the drug nanovectors so that performance in vitro and in vivo can be concisely related to Nanomedicine has gained much interest over the years because these parameters.[19,20,21,22,23,24,25,26,27]
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