The controlled release of marcomolecules from inert polymeric martix devices has been extensively researched by our group. Furthermore, a recently synthesized class of bioerodible polymers, made from the non-peptide linking of typrosine dipeptide derivatives, demonstrates adjuvanticity in both monomeric and polymeric form.
The aim of the proposed research is to develop a controlled release immunization implant which will have a two-fold effect. First, the device will produce sustained, controlled release of antigen in vivo, thereby initiating production of antibody specific for that antigen and successfully immunizing the animal. Second, the products formed during polymer hydrolysis will have an adjuvant effect on the immune response, thus enhancing the level and duration of antibody production and improving protection against subsequent challenge. To achieve this goal: 1) Poly(iminocarbonates) composed of N- and C-blocked derivatives of N-(L-tyrosyl)-L-tyrosine will be synthesized and characterized with regard to molecular weight mechanical properties, surface properties, and degradation behavior; 2) The release of model antigens from devices composed of these polymers will be measured and mathematically modelled; 3) Adsorption-desorption studies of polymer and antigen will be conducted to investigate the """"""""depot"""""""" effect mechanism of adjuvanticity; 4) Polymeric devices containing antigen and polymer-antigen adsorbates will be implanted or injected in mice, and the antigen- specific antibody levels will be measured by ELISA; and 5) Release patterns from devices will be altered with ultrasound or formulation parameters to determine the effect of dosage on adjuvanticity.
| Cohen, S; Bernstein, H; Hewes, C et al. (1991) The pharmacokinetics of, and humoral responses to, antigen delivered by microencapsulated liposomes. Proc Natl Acad Sci U S A 88:10440-4 |
| Mathiowitz, E; Kline, D; Langer, R (1990) Morphology of polyanhydride microsphere delivery systems. Scanning Microsc 4:329-40 |
| Kost, J; Leong, K; Langer, R (1989) Ultrasound-enhanced polymer degradation and release of incorporated substances. Proc Natl Acad Sci U S A 86:7663-6 |
