Encapsulation in nanoparticles improves anti-cancer efficacy of carboplatin

Tanmoy Sadhukha, Swayam Prabha

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

Abstract

Poor cellular uptake contributes to high dose requirement and limited therapeutic efficacy of the platinum-based anticancer drug carboplatin. Delivery systems that can improve the cellular accumulation of carboplatin will, therefore, likely improve its therapeutic potential. The objective of this study was to evaluate nanoparticles composed of the biodegradable polymer, poly(d, l-lactide-co-glycolide), for carboplatin delivery to tumor cells. Carboplatin-loaded nanoparticles were formulated by double emulsion-solvent evaporation technique. Nanoparticles demonstrated sustained release of carboplatin over 7 days. Cellular uptake of carboplatin encapsulated in nanoparticles was several fold higher than that with free carboplatin in A549 (lung) and MA148 (ovarian) tumor cells. In vitro cytotoxicity studies showed that encapsulation of carboplatin in nanoparticles resulted in a remarkable reduction in the IC50 of carboplatin in several cell lines (up to 280-fold in some cells). Confocal microscopic analysis revealed the presence of carboplatin nanoparticles in several cellular compartments including lysosomes, cytoplasm, and the nucleus. These results demonstrate an enhanced cellular uptake of carboplatin through encapsulation in PLGA nanoparticles and suggest that improved therapeutic efficacy and reduced toxicity may be achieved with this approach.

Original languageEnglish (US)
Pages (from-to)1029-1038
Number of pages10
JournalAAPS PharmSciTech
Volume15
Issue number4
DOIs
StatePublished - Aug 2014

Bibliographical note

Funding Information:
We thank the University Imaging Centers at the University of Minnesota for assistance with confocal microscopy. Parts of this work were carried out in the Characterization Facility, University of Minnesota, which receives partial support from NSF through the MRSEC program. We also thank the Dr. Rick Knurr, Geochemical Lab in the Department of Earth Sciences at the University of Minnesota for ICP-MS analysis.

Copyright:
Copyright 2014 Elsevier B.V., All rights reserved.

Keywords

  • carboplatin
  • cell uptake
  • chemotherapy
  • cytotoxicity
  • nanoparticles

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