Pharmaceutical Research

, Volume 18, Issue 3, pp 316–322 | Cite as

Formulation and Evaluation of a Folic Acid Receptor-Targeted Oral Vancomycin Liposomal Dosage Form

  • Keith E. Anderson
  • Lise A. Eliot
  • Bruce R. Stevenson
  • James A. Rogers


Purpose. To demonstrate utility of folic acid-coated liposomes for enhancing the delivery of a poorly absorbed glycopeptide, vancomycin, via the oral route.

Methods. Liposomes prepared as dehydration-rehydration vesicles (DRVs) containing vancomycin were optimized for encapsulation efficiency and stability. A folic acid-poly(ethylene oxide)-cholesterol construct was synthesized for adsorption at DRV surfaces. Liposomes were characterized by differential scanning calorimetry (DSC) and assessed in vitroin the Caco-2 cell model and in vivoin male Sprague-Dawley rats. Non-compartmental pharmacokinetic analysis of vancomycin was conducted after intravenous and oral administration of solution or liposome-encapsulated vancomycin with or without 0.05 mole ratio FA-PEO-Chol adsorbed at liposome surfaces.

Results. Optimal loading of vancomycin (32%) was achieved in DRVs of DSPC:Chol:DCP, 3:1:0.25 mole ratio (m.r.) after liposome extrusion. Liposomes released less than 40% of the entrapped drug after 2 hours incubation in simulated gastrointestinal (GI) fluid and simulated intestinal fluid containing a 10 mM bile salt cocktail. Incorporation of FA-PEO-Chol in liposomes increased drug leakage by 20% but resulted in a 5.7-fold increase in Caco-2 cell uptake of vancomycin. Liposomal delivery significantly increased the area under the curve of oral vancomycin resulting in a mean 3.9-fold and 12.5-fold increase in relative bioavailability for uncoated and FA-PEO-Chol-coated liposomes, respectively, compared with an oral solution.

Conclusions. The design of FA-PEO-Chol-coated liposomes resulted in a dramatic increase in the oral delivery of a moderate-size glycopeptide in the rat compared with uncoated liposomes or oral solution. It is speculated that the cause of the observed effect was due to binding of liposome-surface folic acid to receptors in the GI tract with subsequent receptor-mediated endocytosis of entrapped vancomycin by enterocytes.

folic acid liposomes vancomycin oral targeted delivery Caco-2 


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Copyright information

© Plenum Publishing Corporation 2001

Authors and Affiliations

  • Keith E. Anderson
    • 1
    • 2
  • Lise A. Eliot
    • 1
    • 2
  • Bruce R. Stevenson
    • 3
  • James A. Rogers
    • 1
    • 4
  1. 1.Faculty of Pharmacy and Pharmaceutical SciencesUniversity of AlbertaEdmontonCanada
  2. 2.Ligand Pharmaceuticals Inc.San Diego
  3. 3.Department of Cell Biology and Anatomy, Faculty of MedicineUniversity of AlbertaEdmontonCanada
  4. 4.J.A.R. Pharmaceuticals Ltd.Ed- montonCanada

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