Poly(propyleneimine) dendrimer and dendrosome mediated genetic immunization against hepatitis B

Dutta, T., Garg, M. and Jain, N. K. (2008) Poly(propyleneimine) dendrimer and dendrosome mediated genetic immunization against hepatitis B. Vaccine, 26 27-28: 3389-3394. doi:10.1016/j.vaccine.2008.04.058


Author Dutta, T.
Garg, M.
Jain, N. K.
Title Poly(propyleneimine) dendrimer and dendrosome mediated genetic immunization against hepatitis B
Journal name Vaccine   Check publisher's open access policy
ISSN 0264-410X
1873-2518
Publication date 2008
Sub-type Article (original research)
DOI 10.1016/j.vaccine.2008.04.058
Volume 26
Issue 27-28
Start page 3389
End page 3394
Total pages 6
Editor R. E. Spier
Place of publication Oxford, U. K.
Publisher Elsevier
Collection year 2009
Language eng
Subject C1
860801 Human Biological Preventatives (e.g. Vaccines)
111599 Pharmacology and Pharmaceutical Sciences not elsewhere classified
11 Medical and Health Sciences
1107 Immunology
Abstract The purpose of the present research work is to explore the potential of dendrosomes in genetic immunization against hepatitis B. Plasmid DNA encoding pRc/CMV-HBs[S] (5.6 kb), encoding the small region of the hepatitis B surface antigen, was complexed with 5th generation poly(propyleneimine) dendrimer (PPI) in different ratios. Transfection of CHO cells revealed that a ratio of 1:50 for pDNA:PPI was optimum for transfection. Results of cytotoxicity studies showed that the toxicity of PPI-DNA complex was significantly (p < 0.05) higher for PPI 75 and PPI 100 as compared to the other PPI-DNA complexes. PPI 50 was employed for preparation of dendrosomes by reverse phase evaporation method. The dendrosomal formulation DF3 was found to possess optimum vesicle size, zeta potential and entrapment efficiency. In vitro production of HBsAg in CHO cells showed that DF3 possess maximum transfection efficiency. In vivo immunization studies were carried out by giving a single intramuscular injection of 10 [mu]g of plasmid DNA (pDNA) or its dendrimeric or dendrosomal formulation to female Balb/c mice, followed by estimation of total IgG, IgG1, IgG2a, IgG2b, biweekly. DF3 was found to elicit maximum immune response in terms of total IgG and its subclasses under study as compared to PPI 50 and pDNA at all time points. Animals immunized with DF3 developed very high cytokine level. Higher level of IFN-[gamma] suggests that the immune response was strictly Th1 mediated. Our observations clearly prove the superiority of dendrosomes over PPI-DNA complex and pDNA for genetic immunization against hepatitis B. © 2008 Elsevier Ltd.
Keyword Dendrimer
Dendrosome
Genetic immunization
DNA vaccine
Hepatitis B
Gene delivery
Q-Index Code C1
Q-Index Status Confirmed Code

Document type: Journal Article
Sub-type: Article (original research)
Collections: 2009 Higher Education Research Data Collection
Excellence in Research Australia (ERA) - Collection
School of Pharmacy Publications
 
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Created: Wed, 08 Apr 2009, 09:48:04 EST by Elizabeth Pyke on behalf of School of Pharmacy