Preparation and drug release mechanism of CTS-TAX-NP-MSCs drug delivery system

Int J Pharm. 2013 Nov 1;456(1):186-94. doi: 10.1016/j.ijpharm.2013.07.070. Epub 2013 Aug 7.

Abstract

Targeting delivery of anticancer agents is a promising field in anticancer therapy. Inherent tumor-tropic and migratory properties of mesenchymal stem cells (MSCs) make them potential vehicles for targeting drug delivery systems for tumors. Although, MSCs have been successfully studied and discussed as a vehicle for cancer gene therapy, they have not yet been studied adequately as a potential vehicle for traditional chemical anticancer drugs. In this study, we have engineered MSCs as a potential targeting delivery vehicle for paclitaxel (TAX)-loaded nanoparticles (NPs). The size, surface charge, starving time of MSCs, incubating time and concentration of NPs could influence the efficiency of NPs uptake. In vitro release of TAX from CTS (chitosan)-TAX-NP-MSCs and the expression of P-glycoprotein demonstrated that release of TAX from MSCs might involve both passive diffusion and active transport. In vitro migration assays indicated that MSCs at passage number 3 have the highest migrating ability. Although, the migration ability of CTS-TAX-NP-MSCs could be inhibited by uptake of CTS-TAX-NPs, this ability could recover 6 days after the internalization.

Keywords: Cancer; Drug delivery; Mesenchymal stem cells; Nanoparticle; Vehicle.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism
  • ATP Binding Cassette Transporter, Subfamily G, Member 2
  • ATP-Binding Cassette Transporters / metabolism
  • Animals
  • Antineoplastic Agents, Phytogenic / administration & dosage*
  • Antineoplastic Agents, Phytogenic / chemistry
  • Cell Line, Tumor
  • Cell Movement
  • Chitosan / chemistry
  • Drug Compounding
  • Drug Delivery Systems*
  • Humans
  • Lactic Acid / chemistry
  • Mesenchymal Stem Cells / physiology*
  • Mice
  • Multidrug Resistance-Associated Proteins / metabolism
  • Nanoparticles / chemistry
  • Paclitaxel / administration & dosage*
  • Paclitaxel / chemistry
  • Polyglycolic Acid / chemistry
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Rats
  • Rats, Sprague-Dawley

Substances

  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • ATP Binding Cassette Transporter, Subfamily G, Member 2
  • ATP-Binding Cassette Transporters
  • Abcg2 protein, rat
  • Antineoplastic Agents, Phytogenic
  • Multidrug Resistance-Associated Proteins
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Polyglycolic Acid
  • Lactic Acid
  • Chitosan
  • Paclitaxel
  • multidrug resistance-associated protein 1