Ece Gamsiz, D, Shah, Lipa, Devalapally, Harikrishna, Amiji, Mansoor M and Carrier, Rebecca L (2008) A model predicting delivery of saquinavir in nanoparticles to human monocyte/macrophage (Mo/Mac) cells. Biotechnology and Bioengineering, 101 (5). pp. 1072-1082. ISSN 1097-0290

Abstract

Modeling the influence of a technology such as nanoparticle systems on drug delivery is beneficial in rational formulation design. While there are many studies showing drug delivery enhancement by nanoparticles, the literature provides little guidance regarding when nanoparticles are useful for delivery of a given drug. A model was developed predicting intracellular drug concentration in cultured cells dosed with nanoparticles. The model considered drug release from nanoparticles as well as drug and nanoparticle uptake by the cells as the key system processes. Mathematical expressions for these key processes were determined using experiments in which each process occurred in isolation. In these experiments, intracellular delivery of saquinavir, a low solubility drug dosed as a formulation of poly(ethylene oxide)-modified poly(epsilon- caprolactone) (PEO-PCL) nanoparticles, was studied in THP-1 human monocyte/macrophage (Mo/Mac) cells. The model accurately predicted the enhancement in intracellular concentration when drug was administered in nanoparticles compared to aqueous solution. This simple model highlights the importance of relative kinetics of nanoparticle uptake and drug release in determining overall enhancement of intracellular drug concentration when dosing with nanoparticles.

Item Type:	Article
Related URLs:	http://www.ncbi.nlm.nih.gov/sites/entrez...
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Keywords:	nanoparticles; modeling; drug delivery; THP-1 Mo/Mac cells; PEO-PCL
Related URLs:	http://www.ncbi.nlm.nih.gov/sites/entrez...
Date Deposited:	14 Dec 2009 13:48
Last Modified:	14 Dec 2009 13:48
URI:	https://oak.novartis.com/id/eprint/1326