Use of PBMC Partitioning to Predict RES-Uptake of a Nanoemulsion in a Colon Cancer Xenograft
H. Devalapally, J.D. Clogston, M.M. Amiji, S. McNeil, S.T. Stern
SAIC-Frederick, National Cancer Institute at Frederick, US
Keywords: pharmacokinetics, monocytes, RES-uptake, nanocarriers, colon cancer, paclitaxel
Abstract:Nanotechnology platforms have emerged as versatile carrier systems for delivery of active molecules to tumors. Nanoparticle-based formulations have demonstrated enhanced efficacy and decreased toxicity in comparison to conventional drugs. These carrier systems often encounter rapid uptake by phagocytic cells of the reticuloendothelial system (RES), which is a major obstacle to tumor accumulation. Experimental models are required that can predict RES sequestration, and allow for optimization of nanoparticle properties, such as size, surface charge, and PEGylation. The aim of the present work was to determine the applicability of using peripheral blood mononuclear cell (PBMC) partitioning of nanoparticles as an accessible surrogate for monitoring of RES distributi Paclitaxel (PTX) loaded o/w emulsion was prepared by using Microfluidizer® ¬¬processor M-110EH.PTX-loaded nanoemulsion droplets were reproducibly prepared by the high pressure homogenization method. Blank and drug-containing nanoemulsion droplets had Z-average diameters of 160 and 180 nm, respectively, and corresponding zeta potentials of +70.9 and +73.0 mV. During 4h incubation in whole mouse blood, increased PTX PBMC fractioning (~2 folds) was observed with nanoemulsion in comparison to Taxol TM and Abraxane TM. The pharmacokinetic profile of PTX nanoemulsion in Blood, plasma, liver and spleen followed biphasic decays, with the PBMC fraction and tumor following monophasic decays. In agreement with the in vitro PBMC uptake studies, greater distribution of PTX was found in liver, PBMC and spleen in comparison to Blood, plasma and tumor mass. These data support the hypothesis that uptake into the PBMC fraction in vitro, and in vivo, can be used to estimate distribution of nanoformulations to RES organs.