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Pharmaceutical Research

, Volume 22, Issue 6, pp 962–971 | Cite as

Cyclodextrin-Mediated Drug Release from Liposomes Dispersed Within a Bioadhesive Gel

  • Laïla Boulmedarat
  • Géraldine Piel
  • Amélie Bochot
  • Sylviane Lesieur
  • Luc Delattre
  • Elias Fattal
Research Paper

Purpose

The aim of the present study was to design a new mucosal drug delivery system composed of liposomes dispersed within a bioadhesive hydrogel containing methyl-β-cyclodextrin (MeβCD) for controlled drug release.

Methods

A hydrophilic model molecule, inulin, was encapsulated within positively charged and PEG-ylated liposomes and its release was measured in the presence of MeβCD after vesicle dispersion within the bioadhesive Carbopol® 974P gel. Freeze-fracture electron microscopy (FFEM) was used to follow liposome morphological changes when dispersed within the hydrogel. Liposome-MeβCD interactions were investigated by turbidity monitoring during continuous addition of MeβCD to liposomes and by FFEM.

Results

Inulin diffusion within the gel was influenced by Carbopol® 974P concentration since no gel erosion occurred. When dispersed within the gel, positively charged liposomes displayed a higher stability than PEG-ylated vesicles. In the presence of MeβCD, higher amounts of free inulin were released from liposomes, especially in Carbopol®-free system. MeβCD appeared to diffuse towards lipid vesicles and permeabilized their bilayer allowing inulin leakage. Indeed, freeze-fracture experiments and liposome turbidity monitoring have shown that MeβCD behaved as a detergent behavior, resulting in lipid vesicle solubilization.

Conclusion

MeβCD is able to mediate, within a bioadhesive hydrogel, the release of a liposome-encapsulated molecule allowing further application of this delivery system for mucosal administration.

Key words

cyclodextrins drug modified release gel lipid vesicle solubilization liposomes 

Abbreviations

CHOL

cholesterol

FFEM

freeze-fracture electron microscopy

HEPES

4-(2-hydroxyethyl)piperazine-1-ethanesulfonic acid

MeβCD

methyl-β-cyclodextrin

OD

optical density

PEG

poly(ethylene)glycol

PEG2000-DSPE

1,2 stearoyl-sn-glycero-3-phosphoethanol-amine-N-methoxy[poly-(ethyleneglycol)-2000]

QELS

quasi-elastic light scattering

SA

stearylamine

SPC

soybean phosphatidylcholine

Notes

Acknowledgments

G. Piel is a postdoctoral researcher supported by the FNRS, Brussels, Belgium. L. Boulmedarat was supported by a grant of the Ministry of Research in France. The authors wish to thank H. Chacun for her assistance during experiments with radioactive material.

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Copyright information

© Springer Science + Business Media, Inc. 2005

Authors and Affiliations

  • Laïla Boulmedarat
    • 1
  • Géraldine Piel
    • 2
  • Amélie Bochot
    • 1
  • Sylviane Lesieur
    • 1
  • Luc Delattre
    • 2
  • Elias Fattal
    • 1
  1. 1.UMR CNRS 8612, School of PharmacyUniversity of Paris-SudChâtenay-MalabryFrance
  2. 2.Laboratory of Pharmaceutical Technology, Department of PharmacyUniversity of LiègeLiègeBelgium

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