Biodegradable Polymeric Nanoparticles for Tumor-Selective Tamoxifen Delivery: In Vitro and In Vivo Studies
NORTHEASTERN UNIV BOSTON MA
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This study was performed to evaluate the in-vitro and in-vivo tumor-cellular uptake and biodistribution pattern of tamoxifen when administered intravenously as a simple solution and upon encapsulation into biodegradable, surface-modified polye-caprolactone PCL nanoparticles. PCL MW 15,000 nanoparticles were prepared by the solvent displacement method and characterized for particle sizechange and surface morphology by scanning electron microscopy. We investigated the nanoparticle-surface modification potential of the hydrophilic stabilizer Pluronic Federal Registration F-68 and F-108 employed during the preparation by electron spectroscopy for chemical analysis ESCA. Quantitative in-vitro cellular uptake of tritiated 3H tamoxifen in solution form and as nanoparticulate formulation was assessed in MCF-7 breast cancer cells. In-vivo biodistribution studies for the same formulations were carried out in NuNu mice bearing MDA-MB-231 human breast carcinoma xenograft. Spherical nanoparticles having positive zeta potential 25 mV were obtained in the size range of 200-300 nm. Pluronics both F-68 and F-108, the triblock copolymers of polyethylene oxide PEO and polypropylene oxide induced surface hydrophilization of the nanoparticles via adsorption as evident by ESCA. Nanoparticulate formulations of tamoxifen achieved higher intracellular concentrations when exposed at therapeutic concentrations to tumor cells in-vitro compared to solutions. The in-vivo biodistribution studies carried out in nude mice bearing experimental breast tumor suggested increased tumor concentrations for the drug administered as nanoparticulate formulations besides longer retention times within tumor mass.
- Anatomy and Physiology