Title
Synthesis and Characterization of Novel Silicate Prodrugs and Block Copolymers for Use into Nanoparticle Drug Delivery
Abstract
Silicate ester prodrugs are a novel family of labile prodrugs by which both physical (i.e., solubility) and chemical (i.e., rates of hydrolysis back to the parent drug) characteristics may be easily tuned. Block co-polymers of well-defined composition, namely poly(ethylene glycol)-b-poly(lactic-co-glycolic acid) (PEG-b- PLGA), were synthesized to serve as the drug carrier. These innovative drugs and FDA approved polymers have been effectively coupled with a formulation technique known as flash nanoprecipitation (FNP). FNP of a selected silicate ester prodrug of paclitaxel and PEG-b-PLGA yields nanoparticles of ca. 120 nm diameter and consisting of ca. 50 wt% of the paclitaxel silicate prodrug. An MDA- MB-231 (breast cancer) cell culture assay was used to demonstrate in vitro efficacy of both taxane silicate prodrugs themselves as well as the loaded nanoparticles from FNP. Upon administration to tumor-bearing mice the silicate prodrugs hydrolyze in the tumor microenvironment, thereby releasing the cytotoxic parent drug. Tumor size was monitored via bioluminescence, and the silicate prodrug-containing nanoparticles showed statistically equivalent efficacy (and minimal associated side effects) when compared to equivalent dosings of the commercially used Taxol® and Abraxane®. The silicate chemistry is not specific to the taxane family of drugs. In the second part of thesis I will present recent findings on this front. The scope of the functional groups selected was based upon the availability of the drugs and the novelty of the subsequent silicate functionalization. The general background of each drug and utility will also be discussed.
Description
University of Minnesota Ph.D. dissertation. October 2015. Major: Chemistry. Advisor: Thomas Hoye. 1 computer file (PDF); xxix, 372 pages.
Suggested Citation
Michel, Andrew.
(2015).
Synthesis and Characterization of Novel Silicate Prodrugs and Block Copolymers for Use into Nanoparticle Drug Delivery.
Retrieved from the University of Minnesota Digital Conservancy,
https://hdl.handle.net/11299/175688.