Transdermal delivery of the in situ hydrogels of curcumin and its inclusion complexes of hydroxypropyl-β-cyclodextrin for melanoma treatment

Int J Pharm. 2014 Jul 20;469(1):31-9. doi: 10.1016/j.ijpharm.2014.04.039. Epub 2014 Apr 18.

Abstract

Curcumin (Cur) is a hydrophobic polyphenol with diverse pharmacological effects, especially for cancer treatment. However, its weak water solubility and stability was the major obstacle for the formulation research of Cur. The complexation of Cur and hydroxypropyl-β-cyclodextrin (HP-β-CD) was done by grinding. The increasing solubility of Cur was achieved due to complexation and the photochemical stability of Cur was improved. The inclusion of Cur could happen when two ends of Cur were embedded into the cavity of the HP-β-CD rings. The in situ hydrogels (ISGs) of Cur and its inclusion complexes were prepared using poloxamers 407 and 188 as the matrix. The extent of drug's in vitro release from the ISGs depended on the dissolution of drugs. Both of the ISGs had transdermal effect and cytotoxicity on B16-F10 cells. However, the effects of the ISGs containing Cur inclusion complexes were much higher than those of Cur ISGs because of the improved Cur solubility in the former. The cytotoxicity of Cur on melanoma cells was related to blocking of cellular proliferation in the G2/M stage followed by cellular apoptosis. The ISGs of Cur inclusion complexes are a promising formulation for melanoma treatment.

Keywords: Erosion; In situ hydrogels; Inclusion complexes; Melanoma; Transdermal.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 2-Hydroxypropyl-beta-cyclodextrin
  • Administration, Cutaneous
  • Animals
  • Antineoplastic Agents, Phytogenic / administration & dosage*
  • Antineoplastic Agents, Phytogenic / chemistry
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Chemistry, Pharmaceutical
  • Curcumin / administration & dosage*
  • Curcumin / chemistry
  • Dose-Response Relationship, Drug
  • Drug Carriers*
  • Drug Stability
  • G2 Phase Cell Cycle Checkpoints / drug effects
  • Gels
  • Hydrophobic and Hydrophilic Interactions
  • Kinetics
  • Melanoma, Experimental / drug therapy*
  • Melanoma, Experimental / pathology
  • Mice
  • Poloxamer / chemistry
  • Skin Neoplasms / drug therapy*
  • Skin Neoplasms / pathology
  • Solubility
  • Technology, Pharmaceutical / methods
  • beta-Cyclodextrins / chemistry*

Substances

  • Antineoplastic Agents, Phytogenic
  • Drug Carriers
  • Gels
  • beta-Cyclodextrins
  • Poloxamer
  • 2-Hydroxypropyl-beta-cyclodextrin
  • Curcumin