Investigations on cellular interaction of polyelectrolyte based nano-walled reservoir using MCF-7 cell lines: a novel chemotherapeutic approach

J Pharm Pharmacol. 2009 Dec;61(12):1601-7. doi: 10.1211/jpp/61.12.0003.

Abstract

Objectives: A polyelectrolyte (PE) based nano-walled reservoir (NwR) was developed using alternate deposition of natural polyions on a decomposable core (CaCO(3)). The system was charged with paclitaxel (PTX) using the trigger property of an organic solvent (NwR-PTX). In addition, the surface of the nano-walled reservoir was modified with PE-PEG2000 (NwR-PTX-PEG)) in order to investigate any changes in the interaction of surface-modified polyelectrolyte shells with breast cancer cells, since surface chemistry greatly influences the performance of microcapsules in the biological environment.

Methods: The surface modification was confirmed by differential scanning calorimetry studies, which showed a shifting of the endothermic peak after pegylation. Layer-by-layer (LBL) growth of the system was confirmed by the sequential change in the zeta-potential. The release of paclitaxel from the formulations followed first order kinetics (r(2) = 0.9), indicating matrix diffusion. The interaction of NwR-PTX with MCF-7 cell lines was investigated by coating the system with FITC-dextran (NwR-PTX-FITC) and quantitated using flow cytometry.

Key findings: Cellular uptake of positively charged NwR reached 56% after 4 h and 76% after 24 h. This was reduced significantly after pegylation. The negatively charged NwR reached only 49% after 24 h.

Conclusions: This study opens the possibility of specific targeting of tumour cells that can control the release of chemotherapeutic agent either by means of a physiological or chemical trigger. This suggests potential application of this system as a novel approach for the delivery of chemotherapeutic agents.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents, Phytogenic / chemistry*
  • Antineoplastic Agents, Phytogenic / therapeutic use
  • Biological Transport
  • Breast Neoplasms / drug therapy*
  • Capsules / chemistry
  • Cell Line, Tumor
  • Dextrans / chemistry
  • Drug Carriers / chemistry*
  • Electrolytes / chemistry
  • Female
  • Flow Cytometry
  • Humans
  • Nanostructures / chemistry*
  • Paclitaxel / chemistry*
  • Paclitaxel / therapeutic use
  • Static Electricity

Substances

  • Antineoplastic Agents, Phytogenic
  • Capsules
  • Dextrans
  • Drug Carriers
  • Electrolytes
  • Paclitaxel