Evaluation of synergistic effect of biodegradable polymeric nanoparticles and aluminum based adjuvant for improving vaccine efficacy

Int J Pharm. 2014 Aug 25;471(1-2):377-84. doi: 10.1016/j.ijpharm.2014.05.061. Epub 2014 Jun 2.

Abstract

Aluminum based adjuvants have been used widely to induce long lasting protective immunity through vaccination. But reported incidences of toxicity and side effects of aluminum have raised concerns regarding their safety in childhood vaccines. The present study demonstrates the synergistic effect of admixture of polylactic acid-polyethylene glycol (PLA-PEG) based biodegradable nanoparticles (NPs) and aluminum phosphate as a potential adjuvant system using tetanus toxoid (TT) as a model antigen. The immunological activity of the admixture formulation was maintained up to 180 days of storage at 5 °C±3 °C. Percent adsorption/encapsulation of tetanus toxoid increased to nearly 90% in admixture formulation as compared to 55% in conventional vaccine. Admixture preparation (PLA-PEG-Al 0.2 mg-TT and PLA-Al 0.2 mg-TT) showed 80% and 50% survival respectively, even at 180 days as compared to 30% survival observed in the conventional tetanus vaccine. The present study established the feasibility to formulate a dosage form with improved efficacy and reduced aluminum concentration for vaccination.

Keywords: Adjuvants; Aluminum phosphate; Nanoparticles; PLA; Tetanus; Vaccine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Pharmaceutic / chemistry*
  • Aluminum Compounds / chemistry*
  • Animals
  • Antibodies / blood
  • Biocompatible Materials / chemistry*
  • Drug Carriers / chemistry*
  • Drug Compounding
  • Drug Synergism
  • Lactates / chemistry*
  • Liver / drug effects
  • Liver / pathology
  • Mice
  • Nanoparticles / chemistry*
  • Particle Size
  • Phosphates / chemistry*
  • Polyethylene Glycols / chemistry*
  • Surface Properties
  • Tetanus Toxoid / administration & dosage*
  • Tetanus Toxoid / adverse effects
  • Tetanus Toxoid / immunology

Substances

  • Adjuvants, Pharmaceutic
  • Aluminum Compounds
  • Antibodies
  • Biocompatible Materials
  • Drug Carriers
  • Lactates
  • Phosphates
  • Tetanus Toxoid
  • poly(lactic acid-ethylene glycol)
  • Polyethylene Glycols
  • aluminum phosphate