3. MODEL-BASED ENGINEERING OF POLYMERIC DRUG DELIVERY VEHICLES

Department: Bioengineering
Faculty Advisor(s): David Gough

Primary Student
Name: Lili X Peng
Email: lpeng@ucsd.edu
Phone: 617-501-2865
Grad Year: 2010

Abstract
Polymeric nanoparticles are of great interest as drug carriers due to their potential for simultaneously targeting tumors and limiting drug exposure to normal tissues. The classical method of drug carrier design invokes trial-and-error testing of chemical substances on animals and subsequently matching of effects to treatments. This procedure can be time-consuming and expensive. In our study, we are designing a nanoparticle consisting of a cancer drug, Paclitaxel (PTX), covalently bound to a biopolymer, poly-L-glutamyl-glutamine (pGGA). We use an ab initio approach involving computational modeling spanning the micro-to-mesoscale regimes as a novel alternative. It has been established that the cellular uptake of nanoparticles and depends on physicochemical properties such as size and shape. Non-spherical, disc-like, and cylindrical-shaped particles have been shown to outperform their spherical counterparts while crossing transport barriers in drug delivery. To construct these non-spherical geometries, coarse-grained models of PTX-pGGA were developed by varying the hydrophobic:hydrophilic (PTX:pGGA) mass ratio and covalent attachment sites of PTX on pGGA. These systems were then run for 200ns using the GROMACS and dissipative particle dynamics simulation packages to observe self-assembly of PTX-pGGA into specific geometries. The plan is to demonstrate molecular modeling as a novel tool that allows us to engineer a successful intravenous cancer therapeutic. With this model we expect to suggest optimal physicochemical properties of PTX-pGGA for synthesis and testing.

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