Enhanced immune response with a combination of alum and biodegradable nanoparticles containing tetanus toxoid

• Published in: Journal of microencapsulation 2001-11, Vol.18 (6), p.723-732
• Main Authors: RAGHUVANSHI, R. J, MISTRA, A, TALWAR, G. P, LEVY, R. J, LABHASETWAR, V
• Format: Article
• Language: English
• Subjects: Adjuvants, Immunologic - administration & dosage; Alum Compounds - administration & dosage; Animals; Biocompatible Materials; Biodegradation, Environmental; Biological and medical sciences; Capsules; Delayed-Action Preparations; Drug Carriers; Drug Compounding - methods; Drug Synergism; General pharmacology; Immunoglobulin G - blood; Immunomodulators; Injections, Subcutaneous; Lactic Acid; Medical sciences; Nanotechnology; Particle Size; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Polyglycolic Acid; Polymers; Rats; Rats, Wistar; Tetanus Toxoid - administration & dosage; Tetanus Toxoid - immunology; Vaccine Antibody Response Sustained Release Polymer
• ISSN: 0265-2048; 1464-5246
• DOI: 10.1080/02652040110055261

The purpose of the study was to determine the synergistic adjuvant effect of sustained release biodegradable nanoparticles in combination with alum. Nanoparticles containing tetanus toxoid (TT) were formulated using a biodegradable polymer, polylactic polyglycolic acid co-polymer (50:50, molecular weight 100 000). The immunization studies were carried out subcutaneously in rats. The results were expressed as mean serum anti-TT IgG levels. The nanoparticles demonstrated a TT loading of 4% w/w with mean particle diameter of 238 #45 31 nm. The TT encapsulated in nanoparticles was released slowly under in vitro conditions, with 67.5% cumulative release occurring in 20 days. A single injection of TT-nanoparticles (TT dose=10 Lf) mixed with TT-Alum (TT dose =5 Lf) induced a four-fold greater mean serum anti-TT IgG response than a single injection of TT nanoparticles alone (TT dose=15 Lf) (2235 #45 310 vs. 539 #45 49 #119 g/ml, mean #45 sem, p => 0.001). In addition, the mean immune response induced with the single injection of combination of nanoparticles and alum was comparable to the two injections of TT-alum alone (5 Lf each dose) given at 3 week intervals IgG = 1998 #45 333 #119 g/ ml). Furthermore, the combination induced a peak immune response (IgG = 4215 #45 546 #119 g/ml) as early as the first time point at 3 weeks post-immunization. In the case of a TT-alum alone, the animals showed a weaker immune response at 3 weeks and required a second dose of TT-alum to enhance the antibody response. The data thus suggest that the combination of TTnanoparticles and TT-alum acts as a much better adjuvant than nanoparticles or alum alone. A rapid induction of immune response is useful to curb the spread of communicable diseases in the case of an outbreak.