Surfactant vesicle-mediated delivery of DNA vaccines via the subcutaneous route

Y Perrie, J E Barralet, S McNeil, A Vangala

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Compared to naked DNA immunisation, entrapment of plasmid-based DNA vaccines into liposomes by the dehydration-rehydration method has shown to enhance both humoural and cell-mediated immune responses to encoded antigens administered by a variety of routes. In this paper we have compared the potency of lipid-based and non-ionic surfactant based vesicle carrier systems for DNA vaccines after subcutaneous immunisation. Plasmid pI.18Sfi/NP containing the nucleoprotein (NP) gene of A/Sichuan/2/87 (H3N2) influenza virus in the pI.18 expression vector was incorporated by the dehydration-rehydration method into various vesicle formulations. The DRV method, entailing mixing of small unilamellar vesicles (SUV) with DNA, followed by dehydration and rehydration, yielded high DNA vaccine incorporation values (85-97% of the DNA used) in all formulations. Studies on vesicle size revealed lipid-based systems formed cationic submicron size vesicles whilst constructs containing a non-ionic surfactant had significantly large z-average diameters (>1500 nm). Subcutaneous vesicle-mediated DNA immunisation employing two DRV(DNA) formulations as well as naked DNA revealed that humoural responses (immunoglobulin total IgG, and subclasses IgG1 and 1gG2a) engendered by the plasmid encoded nucleoprotein were substantially higher after dosing twice, 28 days apart with 10 microg DRV-entrapped DNA compared to naked DNA. Comparison between the lipid and non-ionic based vesicle formulations revealed no significant difference in stimulated antibody production. These results suggest that, not only can DNA be effectively entrapped within a range of lipid and non-ionic based vesicle formulations using the DRV method but that such DRV vesicles containing DNA may be a useful system for subcutaneous delivery of DNA vaccines.

LanguageEnglish
Pages31-41
Number of pages11
JournalInternational Journal of Pharmaceutics
Volume284
Issue number1-2
DOIs
Publication statusPublished - 13 Oct 2004

Fingerprint

DNA Vaccines
Surface-Active Agents
DNA
Nucleoproteins
Fluid Therapy
Dehydration
Lipids
Immunization
Plasmids
Immunoglobulin G
H3N2 Subtype Influenza A Virus
Unilamellar Liposomes
Orthomyxoviridae
Liposomes
Antibody Formation
Immunoglobulins
Antigens

Keywords

  • vaccine
  • drug delivery systems
  • liposomes
  • subcutaneous injections

Cite this

Perrie, Y ; Barralet, J E ; McNeil, S ; Vangala, A. / Surfactant vesicle-mediated delivery of DNA vaccines via the subcutaneous route. In: International Journal of Pharmaceutics. 2004 ; Vol. 284, No. 1-2. pp. 31-41.
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Surfactant vesicle-mediated delivery of DNA vaccines via the subcutaneous route. / Perrie, Y; Barralet, J E; McNeil, S; Vangala, A.

In: International Journal of Pharmaceutics, Vol. 284, No. 1-2, 13.10.2004, p. 31-41.

Research output: Contribution to journalArticle

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