2-Hydroxypropyl-β-cyclodextrin-modified SLN of paclitaxel for overcoming p-glycoprotein function in multidrug-resistant breast cancer cells

J Pharm Pharmacol. 2013 Jan;65(1):72-8. doi: 10.1111/j.2042-7158.2012.01578.x. Epub 2012 Aug 13.

Abstract

Objectives: This study aimed to evaluate the potential of solid lipid nanoparticles (SLNs) of paclitaxel (PTX) modified with a 2-hydroxypropyl-β-cyclodextrin system to enhance cellular accumulation of PTX into p-glycoprotein (p-gp)-expressing cells.

Methods: The PTX-loaded-SLNs consisted of lipid (stearic acid) and surfactants (lecithin and poloxamer 188) and were then modified with 2-hydroxypropyl-β-cyclodextrin by a sonication method.

Key findings: In terms of cytotoxicity, PTX-loaded SLNs modified with 2-hydroxypropyl-β-cyclodextrin showed higher cytotoxicity than other formulations. In particular, the cellular uptake of PTX from PTX-loaded SLNs modified with 2-hydroxypropyl-β-cyclodextrin was about 5.8- and 1.5-fold higher than that from PTX solution and unmodified PTX-loaded SLNs in MCF-7/ADR cells, respectively. After a 4-h incubation, clear fluorescence images inside cells were observed over time. When PTX-loaded SLNs modified with 2-hydroxypropyl-β-cyclodextrin were incubated with MCF-7/ADR cells for 4 h, cellular uptake of PTX increased 1.7-fold versus that of PTX in the presence of verapamil.

Conclusions: These results suggest that optimized SLNs modified with 2-hydroxypropyl-β-cyclodextrin may have potential as an oral drug delivery system for PTX.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 2-Hydroxypropyl-beta-cyclodextrin
  • ATP Binding Cassette Transporter, Subfamily B
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism
  • Antineoplastic Agents, Phytogenic / administration & dosage
  • Antineoplastic Agents, Phytogenic / chemistry
  • Antineoplastic Agents, Phytogenic / metabolism
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Biological Transport / drug effects
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Calcium Channel Blockers / pharmacology
  • Cell Survival / drug effects
  • Chemistry, Pharmaceutical
  • Drug Delivery Systems*
  • Drug Resistance, Multiple / drug effects
  • Drug Resistance, Neoplasm* / drug effects
  • Excipients / chemistry
  • Female
  • Humans
  • MCF-7 Cells
  • Nanoparticles / chemistry*
  • Neoplasm Proteins / metabolism
  • Paclitaxel / administration & dosage
  • Paclitaxel / chemistry
  • Paclitaxel / metabolism
  • Paclitaxel / pharmacology*
  • Stearic Acids / chemistry
  • Surface-Active Agents / chemistry
  • Ultrasonics
  • Verapamil / pharmacology
  • beta-Cyclodextrins / chemistry*

Substances

  • ABCB1 protein, human
  • ATP Binding Cassette Transporter, Subfamily B
  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Antineoplastic Agents, Phytogenic
  • Calcium Channel Blockers
  • Excipients
  • Neoplasm Proteins
  • Stearic Acids
  • Surface-Active Agents
  • beta-Cyclodextrins
  • 2-Hydroxypropyl-beta-cyclodextrin
  • stearic acid
  • Verapamil
  • Paclitaxel