Two-Step Delivery: Exploiting the Partition Coefficient Concept to Increase Intratumoral Paclitaxel Concentrations In vivo Using Responsive Nanoparticles
Year: 2016
Type: article
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.
Source: Scientific Reports
DOI: 10.1038/srep18720
Authors: Aaron H. Colby, Rong Liu, Morgan D. Schulz, Robert F. Padera, Yolonda L. Colson, Mark W. Grinstaff
Institutions: Boston University, Brigham and Women's Hospital
Language: English
Subfield: Biomaterials
Field: Materials Science
Domain: Physical Sciences
Open Access status: gold
Estimated APC paid: $2,690
OpenAlex ID: W2227449349