Aquated cisplatin and heparin-pluronic nanocomplexes exhibiting sustainable release of active platinum compound and NCI-H460 lung cancer cell antiproliferation

J Biomater Sci Polym Ed. 2016;27(8):709-20. doi: 10.1080/09205063.2016.1154239. Epub 2016 Apr 1.

Abstract

In recent decades, platinum compounds have been many contributions in medicine. Development of new drugs from the active platinum compounds as well as nanocarriers for targeted delivery and reducing side effects of the drugs has paid much attention. In the study, nanocomplexes were prepared from aquated species of cisplatin and pluronic-conjugated heparin which distributed in the range of 80-100 nm by Transmission Electron Microscopy and 134 nm by Dynamic light scattering (DLS). Formation of the complex was confirmed by FTIR and DLS. The nanocomplexes exhibited high drug-loading capacity (approximately 42.5% wt/wt at 37 °C and 37.5% wt/wt at 25 °C). In vitro, drug-loaded nanogels showed much slower release profiles of cisplatin CDDP in pH 7.4 (physiological pH) compared with pH 5.5 condition at 37 °C. Moreover, the cytotoxicity assay results also indicated that Hep-F127 was cytocompatible; meanwhile, CDDP-loaded nanocomplex was able to reduce the cytotoxic ability of free CDDP (IC50 = 5.68 ± 0.73 μg/ml), which still maintain a significantly antiproliferative activity on NCI-H460 lung cancer cell. The in vitro preliminarily obtained results indicate that the nanocomplex is a candidate for CDDP delivery which can be studied further in cancer therapy.

Keywords: Thermosensitive; cisplatin (CDDP); delivery; heparin–pluronic; nanocomplex.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cisplatin / administration & dosage
  • Cisplatin / chemistry*
  • Cisplatin / pharmacology*
  • Delayed-Action Preparations
  • Drug Carriers / chemistry
  • Heparin / chemistry*
  • Humans
  • Hydrogen-Ion Concentration
  • Hydrophobic and Hydrophilic Interactions
  • Lung Neoplasms / pathology*
  • Nanostructures / chemistry*
  • Poloxamer / chemistry*
  • Sulfates / chemistry
  • Water / chemistry*

Substances

  • Antineoplastic Agents
  • Delayed-Action Preparations
  • Drug Carriers
  • Sulfates
  • Water
  • Poloxamer
  • Heparin
  • Cisplatin