Integrity of liposomes in presence of cyclodextrins: effect of liposome type and lipid composition

Int J Pharm. 2007 Mar 21;333(1-2):167-76. doi: 10.1016/j.ijpharm.2006.09.059. Epub 2006 Oct 10.

Abstract

Liposome stability during incubation in presence of cyclodextrins (CDs) is studied. Dried-rehydrated vesicle (DRV), multilamellar vesicle (MLV) and small unilamellar vesicle (SUV) calcein-encapsulating liposomes, composed of different lipids are formulated, and retention of calcein is followed during vesicle incubation in hydroxypropyl-beta-CD (HP beta-CD), HP gamma-CD or methyl-beta-CD (Me beta-CD), for 24h. Results demonstrate that liposome integrity in cyclodextrins is affected by lipid composition and type. For the same lipid composition calcein release from vesicles is faster in the order: MLV > DRV > SUV. Me beta-CD influences liposome stability most, compared to the other CD's studied. Vesicles composed of saturated phospholipids were found more stable compared to phosphatidyl-choline (PC) liposomes, suggesting that phospholipid saturation and membrane rigidity influences the interaction between liposomal-lipids and CD molecules. Chol (cholesterol) addition in lipid membrane improves PC-liposome integrity, but has opposite or no effect on liposomes consisting of saturated lipids. Decrease of vesicle dispersion turbidity and size distribution in presence of CD, implies that Me beta-CD induces vesicle disruption and solubilization (to micelles). Turbidity measurements confirm that DRV liposomes are affected more than SUV.

Publication types

  • Comparative Study

MeSH terms

  • 2-Hydroxypropyl-beta-cyclodextrin
  • Chemistry, Pharmaceutical
  • Cholesterol / chemistry
  • Cyclodextrins / chemistry*
  • Drug Compounding
  • Excipients / chemistry*
  • Fluoresceins / chemistry
  • Fluorescent Dyes / chemistry
  • Lipids / chemistry*
  • Liposomes*
  • Membrane Fluidity
  • Nanotechnology
  • Nephelometry and Turbidimetry
  • Particle Size
  • Phosphatidylcholines / chemistry
  • Solubility
  • Technology, Pharmaceutical
  • Time Factors
  • beta-Cyclodextrins / chemistry
  • gamma-Cyclodextrins / chemistry

Substances

  • Cyclodextrins
  • Excipients
  • Fluoresceins
  • Fluorescent Dyes
  • Lipids
  • Liposomes
  • Phosphatidylcholines
  • beta-Cyclodextrins
  • gamma-Cyclodextrins
  • hydroxypropyl-gamma-cyclodextrin
  • methyl-beta-cyclodextrin
  • 2-Hydroxypropyl-beta-cyclodextrin
  • Cholesterol
  • 1,2-distearoyllecithin
  • fluorexon