1. Academic Validation
  2. Three-step tumor targeting of paclitaxel using biotinylated PLA-PEG nanoparticles and avidin-biotin technology: Formulation development and in vitro anticancer activity

Three-step tumor targeting of paclitaxel using biotinylated PLA-PEG nanoparticles and avidin-biotin technology: Formulation development and in vitro anticancer activity

  • Eur J Pharm Biopharm. 2008 Sep;70(1):66-74. doi: 10.1016/j.ejpb.2008.04.018.
Mika Pulkkinen 1 Jere Pikkarainen Thomas Wirth Tommy Tarvainen Vesa Haapa-aho Harri Korhonen Jukka Seppälä Kristiina Järvinen
Affiliations

Affiliation

  • 1 Department of Pharmaceutics, University of Kuopio, Kuopio, Finland. Mika.Pulkkinen@uku.fi
Abstract

Despite recent advances in Cancer therapy, many malignant tumors still lack effective treatment and the prognosis is very poor. Paclitaxel is a potential Anticancer drug, but its use is limited by the facts that paclitaxel is a P-gp substrate and its aqueous solubility is poor. In this study, three-step tumor targeting of paclitaxel using biotinylated PLA-PEG nanoparticles and avidin-biotin technology was evaluated in vitro as a way of enhancing delivery of paclitaxel. Paclitaxel was incorporated both in biotinylated (BP) and non-biotinylated (LP) PEG-PLA nanoparticles by the interfacial deposition method. Small (mean size approximately 110 nm), spherical and slightly negatively charged (-10 mV) BP and LP nanoparticles achieving over 90% paclitaxel incorporation were obtained. The successful biotinylation of nanoparticles was confirmed in a novel streptavidin assay. BP nanoparticles were targeted in vitro to brain tumor (glioma) cells (BT4C) by three-step avidin-biotin technology using transferrin as the targeting ligand. The three-step targeting procedure increased the anti-tumoral activity of paclitaxel when compared to the commercial paclitaxel formulation Taxol and non-targeted BP and LP nanoparticles. These results indicate that the efficacy of paclitaxel against tumor cells can be increased by this three-step targeting method.

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