(555h) Engineering PEO-Pdlla Nanoparticles Containing the PI3K Inhibitor LY294002

Authors: 
Fergusson, A., Virginia Tech
Davis, R. M., Virginia Tech
Jo, A., Macromolecules Innovation Institute
The PI3K pathway is critical for many cellular processes from cell cycle regulation and apoptosis to DNA repair. The PI3K pathway also happens to be one of the most consistently dysregulated signaling pathways in cancer cells (1). Targeting this pathway has the potential to create more effective therapies for a variety of neoplastic diseases. LY294002 is a PI3K inhibitor that has shown promise in in vitro models but has not successfully transitioned to in vivo models due to its poor water solubility. We hypothesized that encapsulating LY294002 into polymer nanoparticle using the Flash Nanoprecipitation (FNP) technique would lead to high drug loadings and overcome the current barrier preventing in vivo studies.

Poly(ethylene oxide)-b-poly(D,L lactic acid) (PEO-PDLLA) nanoparticles containing LY294002 loaded at > 10 wt% were fabricated using FNP with sizes ranging from ~ 150 – 250 nm and zeta potentials > -20 mV in DI water. The PEO and PDLLA molecular weights in the diblock copolymer result in PEO brush layers at the particles’ surface and steric stabilization. This drug delivery system has sufficient LY294002 loading to provide clinically relevant LY294002 dosing and allows for the translation of LY294002 into the in vivo setting. This presentation will focus on the design, synthesis, and characterization of these nanoparticles. The flexible particle fabrication methods described here can be applied to a wide range of therapeutic agents, and the use of FNP allows for future scale-up of nanoparticle production.

  1. Fruman DA, Rommel C. PI3K and cancer: lessons, challenges and opportunities. Nat Rev Drug Discov. 2014;13(2):140-56. doi: 10.1038/nrd4204. PubMed PMID: WOS:000331145900018.