Biodegradable Polymeric Nanoparticles for Tumor-Selective Tamoxifen Delivery: In Vitro and In Vivo Studies

Abstract

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 poly(e-caprolactone) (PCL) nanoparticles. PCL (MW ^ 15,000) nanoparticles were prepared by the solvent displacement method and characterized for particle size/change 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 Nu/Nu 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 poly(ethylene oxide) (PEO) and poly(propylene 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.

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Document Details

Document Type
Technical Report
Publication Date
Jan 01, 2005
Accession Number
ADP019748

Entities

People

  • Dinesh B. Shenoy
  • Jugminder S. Chawla
  • Mansoor M. Amiji

Organizations

  • Northeastern University

Tags

DTIC Thesaurus Topics

  • Alkenes
  • Breast Cancer
  • Cells
  • Chemical Compounds
  • Chemical Synthesis
  • Chemistry
  • Ethylene Oxide
  • Ethylenes
  • Health Services
  • High Resolution
  • Hydrocarbons
  • Materials
  • Materials Science
  • Nanoparticles
  • Neoplasms
  • Oxides
  • Polymers

Readers

  • Electrochemical Engineering/ Fuel Cell Technologies
  • Nanocomposite Materials Science
  • Oncology (Cancer Research).

Technology Areas

  • Biotechnology
  • Biotechnology - Cancer Biotech
  • Microelectronics