Preparation and in-vitro/in-vivo evaluation of surface-modified poly (lactide-co-glycolide) fluorescent nanoparticles

J Pharm Pharmacol. 2010 Apr;62(4):422-9. doi: 10.1211/jpp.62.04.0003.

Abstract

Objective: The aim was to develop biodegradable nanoparticles suitable for cellular delivery of chemotherapeutic drugs.

Methods: Poly (lactide-co-glycolide) (PLGA) nanoparticles were prepared using a modified solvent evaporation method. Chitosan and calcium chloride were tested as surface modifiers. Coumarin-6 was incorporated into some formulations as a fluorescent marker.

Key findings: The median size of the particles was between 400 nm and 7 microm, and scanning electron microscope pictures showed that the particles were smooth and spherical. The zeta potentials of the particles with and without surface modifier ranged between -25.7 mV and -7.0 mV, respectively. Fluorescence microscopy and flow cytometry (FACS) analysis showed that smaller surface-modified particles were efficiently internalised by neoplastic 4T1 cells. Image analysis of frozen tissue sections from Balb/c mice given nanoparticles via the tail vein showed that the particles were distributed preferentially into the lungs, followed by the liver, spleen, kidney and heart.

Conclusions: Chitosan-modified PLGA nanoparticles showed significant uptake by neoplastic 4T1 cells, and were distributed to several major organs frequently seen as sites of cancer metastasis in mice.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Biological Transport
  • Breast Neoplasms / metabolism*
  • Cell Line, Tumor
  • Chitosan
  • Coumarins
  • Drug Carriers / chemistry*
  • Drug Carriers / pharmacokinetics*
  • Female
  • Flow Cytometry
  • Fluorescence*
  • Lactic Acid / chemistry*
  • Mice
  • Mice, Inbred BALB C
  • Microscopy, Electron, Scanning
  • Nanoparticles*
  • Particle Size
  • Polyglycolic Acid / chemistry*
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Spectrometry, Fluorescence
  • Surface Properties
  • Technology, Pharmaceutical / methods*
  • Thiazoles
  • Tissue Distribution

Substances

  • Coumarins
  • Drug Carriers
  • Thiazoles
  • coumarin 6
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Polyglycolic Acid
  • Lactic Acid
  • Chitosan