Two-Step Delivery: Exploiting the Partition Coefficient Concept to Increase Intratumoral Paclitaxel Concentrations In vivo Using Responsive Nanoparticles.

Abstract	Drug dose, high local target tissue concentration, and prolonged duration of exposure are essential criteria in achieving optimal drug performance. However, systemically delivered drugs often fail to effectively address these factors with only fractions of the injected dose reaching the target tissue. This is especially evident in the treatment of peritoneal cancers, including mesothelioma, ovarian, and pancreatic cancer, which regularly employ regimens of intravenous and/or intraperitoneal chemotherapy (e.g., gemcitabine, cisplatin, pemetrexed, and paclitaxel) with limited results. Here, we show that a "two-step" nanoparticle (NP) delivery system may address this limitation. This two-step approach involves the separate administration of NP and drug where, first, the NP localizes to tumor. Second, subsequent administration of drug then rapidly concentrates into the NP already stationed within the target tissue. This two-step method results in a greater than 5-fold increase in intratumoral drug concentrations compared to conventional "drug-alone" administration. These results suggest that this unique two-step delivery may provide a novel method for increasing drug concentrations in target tissues.
Authors	Aaron H Colby, Rong Liu, Morgan D Schulz, Robert F Padera, Yolonda L Colson, Mark W Grinstaff
Journal	Scientific reports (Sci Rep) Vol. 6 Pg. 18720 (Jan 07 2016) ISSN: 2045-2322 [Electronic] England
PMID	26740245 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References	Antineoplastic Agents, Phytogenic Drug Carriers Paclitaxel
Topics	Animals Antineoplastic Agents, Phytogenic (administration & dosage, pharmacokinetics) Cell Line, Tumor Disease Models, Animal Drug Carriers Drug Delivery Systems Female Humans Hydrogen-Ion Concentration Hydrophobic and Hydrophilic Interactions Mesothelioma (drug therapy, pathology) Mice Nanoparticles (chemistry) Neoplasms (drug therapy, pathology) Paclitaxel (administration & dosage, pharmacokinetics) Xenograft Model Antitumor Assays

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