Authors: Manish Diwan; Praveen Elamanchili; Min Cao; John Samuel

Source: Current Drug Delivery, Volume 1, Number 4, October 2004 , pp. 405-412(8)

Publisher: Bentham Science Publishers

Abstract:

The main objective of these studies was to investigate whether the nanoparticle delivery has any immunopotentiation effect at modest doses of a few micro- or nanograms of CpG oligodeoxynucleotide (CpG ODN) and what would be the influence on T cell responses at such low doses. Various doses (5 to 0.05 g) of a model CpG ODN adjuvant (#1826) along with 2 Lf tetanus toxoid (TT) were formulated in either nanoparticles using poly(D,L-lactic-coglycolic acid) (PLGA) 50:50 co-polymer, or saline. Strong antigen specific ex vivo T cell proliferation was observed for the Balb / c mice receiving immunogens in nanoparticles. At 5 g dose of CpG ODN, the T cell stimulation index (SI) was 241 as compared with 74 for the same dose when given in saline. Comparable SI value of 78 was observed at 100-fold lower dose (0.05 g) using nanoparticles. Similarly, significantly higher (P<0.01) cytokine secretion was observed for nanoparticles groups. A ten-fold lower dose (0.5 g instead of 5 g) of CpG ODN in nanoparticles was adequate to obtain levels of IFN-, TNF-, and IL-2 comparable to those observed following immunisations in saline. The immunopotentiation effect of the particulate delivery on antibody response (total IgG and subtypes) was not so marked. These studies emphasise that antigen delivery in biodegradable nanoparticles can facilitate induction of strong T cell responses, particularly of the Th1 type, at extremely lower doses of CpG ODN. Such reduction in the effective dose would be advantageous for minimising the potential side effects of these novel adjuvants.

Keywords: cpg dna; immunostimulatory cpg motifs; nanospheres; vaccine delivery; plga

Document Type: Review article

DOI: http://dx.doi.org/10.2174/1567201043334597

Affiliations: 1: Faculty of Pharmacy and Pharmaceutical Sciences, 3118 Dentistry Pharmacy Center, University of Alberta, Edmonton, T6G 2N8, Canada.

Publication date: 2004-10-01

More about this publication?

• The aim of Current Drug Delivery is to publish peer-reviewed articles, short communications, short and in-depth reviews in the rapidly developing field of drug delivery. Modern drug research aims to build in delivery properties of a drug at the design phase, however in many cases this ideal cannot be met and the development of delivery systems becomes as important as the development as the drugs themselves.
  
  The journal aims to cover the latest outstanding developments in drug and vaccine delivery employing physical, physico-chemical and chemical methods. The drugs include a wide range of bioactive compounds from simple pharmaceuticals to peptides, proteins, nucleotides, nucleosides and sugars. The journal will also report progress in the fields of transport routes and mechanisms including efflux proteins and multi-drug resistance.
  
  The journal is essential for all pharmaceutical scientists involved in drug design, development and delivery.

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