• Formulation Develoment and Characaterization of Polycaprolacton/Pluronic F108 NanoParticles for Targeted Breast Cancer Therapy

      Chandran, Thripthy; College of Pharmacy
      Breast Cancer ranks first among cancer deaths for women after malignant lung cancer in the United States. Despite the major advancements in the treatment of breast cancer, it still poses a major challenge. While chemotherapeutic intervention remains the major treatment approach fr cancer, they suffer from several drawbacks including dose limiting toxicity, non-specific biodistribution, and emergence of resistance in solid tumors, thus posing a risk of relapse. Furthermore, the excipients used for the administration of the anticancer agents also cause several undesirable systemic effects such as nephrotoxicity, neurotoxicity, and hypersensitivity reactions when given intravenously. Biodegradable polymeric nanoparticles have emerged as promising targeted drug delivery systems for the delivery of anticancer drug owing to their size characteristics., their ability to passively accumulate by Enhanced Permeability and Retention (EPR) effect in the tumors, ability to protect the active ingredients from degradation, providing a controlled/sustained release of the active ingredients and b tunable for the attachment of active ligands according to a patient's tumor profile and thus provide a personalized therapy. In this study, we designed polymeric nanoparticles for the delivery of anticancer agent docetaxel using poly-e-caprolactone (PCL), which forms the core of the the nanopartilces. Pluronic polymer F108 is used as an emulsifying agent/stabilizer for the PCL nanoparticles, providing a hydrophilic PEG coating thus stealth properties to the nanoparticles. The passive targeting ability of the nanoparticles is evaluated using a near infrared carbocyanine dye (Dir). Trastuzmab is used as an active targeting ligand to target the HER-2 receptors present on the human breast cancer BT-474 cells. Thus, this project focuses on the formulation development, in vitro characterization of docetaxel loaded nanoparticles and finally the characterization of trastuzumab conjugated nanoparticles.