Controlled Delivery of Diphtheria Toxoid Using Biodegradable Poly(D,L-Lactide) Microcapsules

Diphtheria toxoid, which is an important vaccine in the expanded program of immunization (EPI) in the developing countries, was microencapsulated using poly(D,L,-lactide) of 49,000 molecular weight and the in-water drying technique. The microcapsules were subjected to an in vitro antigen release study using a sensitive enzyme-linked immunosorbent assay (ELISA) developed in the laboratory. Antibody titers in immunized Balb/C mice were also determined using direct ELISA. The antibody units in the immunized group till day 75 were quite comparable to those in the group receiving conventional three-dose injection of diphtheria toxoid with calcium phosphate as an adjuvant. SEM photographs of the micro-capsules during in vitro degradation demonstrated the erosion kinetics of the polymer, leading to controlled release of the antigen.

[1]  B. Hederstedt,et al.  The immunization of adults against diphtheria in Sweden. , 1987, Journal of biological standardization.

[2]  R. K. Rana,et al.  Controlled Release of Interleukin-2 from Biodegradable Microspheres , 1990, Bio/Technology.

[3]  R. Langer [4] Polymers for the sustained release of macromolecules: Their use in a single-step method of immunization , 1981 .

[4]  T. Kondo,et al.  Mechanism of hydrolytic degradation of poly(L-lactide) microcapsules: effects of pH, ionic strength and buffer concentration. , 1986, Journal of microencapsulation.

[5]  M. Tuttle,et al.  Controlled release of water-soluble macromolecules from bioerodible hydrogels. , 1983, Biomaterials.

[6]  G. E. Visscher,et al.  Biodegradation of and tissue reaction to poly(DL-lactide) microcapsules. , 1986, Journal of biomedical materials research.

[7]  L. Ljungqvist,et al.  Quantitative estimation of diphtheria and tetanus toxoids. 2. Single radial immuno-diffusion tests (Mancini) and rocket immuno-electrophoresis test in comparison with the flocculation test. , 1987, Journal of biological standardization.

[8]  J. Lyng Quantitative estimation of diphtheria and tetanus toxoids. 4. Toxoids as international reference materials defining Lf-units for diphtheria and tetanus toxoids. , 1990, Biologicals : journal of the International Association of Biological Standardization.

[9]  M. W. Bentzon,et al.  The quantitative estimation of diphtheria and tetanus toxoids. 1. The flocculation test and the Lf-unit. , 1987, Journal of biological standardization.

[10]  M. Goosen,et al.  Kinetics of protein diffusion from a poly(D,L-lactide) reservoir system. , 1990, Journal of pharmaceutical sciences.

[11]  T. Kondo,et al.  Transfer of protons from bulk solution to the surface of poly(L-lactide) microcapsules. , 1986, Journal of Microencapsulation.

[12]  B. Říhová,et al.  Biological properties of targetable poly[N-(2-hydroxypropyl)-methacrylamide]-antibody conjugates☆ , 1985 .

[13]  H. B. Hopfenberg,et al.  Controlled Release from Erodible Slabs, Cylinders, and Spheres , 1976 .

[14]  Donald L. Wise,et al.  Opportunities and challenges in the design of implantable biodegradable polymeric systems for the delivery of antimicrobial agents and vaccines , 1988 .

[15]  Thomas R. Tice,et al.  Controlled vaccine release in the gut-associated lymphoid tissues. I. Orally administered biodegradable microspheres target the peyer's patches , 1990 .

[16]  F. Hutchinson,et al.  Biodegradable polymers for the sustained release of peptides. , 1985, Biochemical Society transactions.

[17]  J. Benoit,et al.  In vitro and in vivo degradation of poly(D,L lactide/glycolide) type microspheres made by solvent evaporation method. , 1989, Biomaterials.

[18]  V. Šubr,et al.  Release of macromolecules and daunomycin from hydrophilic gels containing enzymatically degradable bonds. , 1990, Journal of biomaterials science. Polymer edition.