Nanohybrid systems of non-ionic surfactant inserting liposomes loading paclitaxel for reversal of multidrug resistance

Int J Pharm. 2012 Jan 17;422(1-2):390-7. doi: 10.1016/j.ijpharm.2011.10.003. Epub 2011 Oct 6.

Abstract

Three new nanohybrid systems of non-ionic surfactant inserting liposomes loading paclitaxel (PTX) (NLPs) were prepared to overcome multidrug resistance (MDR) in PTX-resistance human lung cancer cell line. Three non-ionic surfactants, Solutol HS 15 (HS-15), pluronic F68 (PF-68) and cremophor EL (CrEL) were inserted into liposomes by film hydration method to form NLPs with an average size of around 110, 180 and 110 nm, respectively. There was an obvious increase of rhodamin 123 (Rh123) accumulation in A549/T cells after treated with nanohybrid systems loading Rh123 (NLRs) when compared with free Rh123 or liposomes loading Rh123 without surfactants (LRs), which indicated the significant inhibition effects of NLRs on drug efflux. The P-gp detection and ATP determination demonstrated that BNLs could not only interfere P-gp expression on the membrane of drug resistant cells, but also decrease ATP level in the cells. The cytotoxicity of NLPs against A549/T cells was higher than PTX loaded liposomes without surfactants (LPs), and the best result was achieved after treated with NLPs2. The apoptotic assay and the cell cycle analysis showed that NLPs could induce more apoptotic cells in drug resistant cells when compared with LPs. These results suggested that NLPs could overcome MDR by combination of drug delivery, P-gp inhibition and ATP depletion, and showed potential for treatment of MDR.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / antagonists & inhibitors
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism
  • Adenosine Triphosphate / metabolism
  • Antineoplastic Agents, Phytogenic / chemistry
  • Antineoplastic Agents, Phytogenic / metabolism
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Apoptosis / drug effects
  • Cell Cycle / drug effects
  • Cell Line, Tumor
  • Chemistry, Pharmaceutical
  • Dose-Response Relationship, Drug
  • Drug Compounding
  • Drug Resistance, Multiple*
  • Drug Resistance, Neoplasm*
  • Glycerol / analogs & derivatives
  • Glycerol / chemistry
  • Humans
  • Lipids / chemistry*
  • Liposomes
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology*
  • Nanotechnology*
  • Paclitaxel / chemistry
  • Paclitaxel / metabolism
  • Paclitaxel / pharmacology*
  • Particle Size
  • Poloxamer / chemistry
  • Polyethylene Glycols / chemistry
  • Rhodamine 123 / metabolism
  • Solubility
  • Stearic Acids / chemistry
  • Surface-Active Agents / chemistry*
  • Technology, Pharmaceutical / methods*
  • Time Factors

Substances

  • ABCB1 protein, human
  • ATP Binding Cassette Transporter, Subfamily B
  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Antineoplastic Agents, Phytogenic
  • Lipids
  • Liposomes
  • Stearic Acids
  • Surface-Active Agents
  • Poloxamer
  • Rhodamine 123
  • Polyethylene Glycols
  • Solutol HS 15
  • cremophor EL
  • Adenosine Triphosphate
  • Paclitaxel
  • Glycerol