Controlled Antibody Delivery Systems

Abstract

We have developed methods for controlling the release of antibodies (Ab) from biocompatible polymers. Human Ab, human Ab fragments, and mouse monoclonal antibody (mAb) directed against human chorionic gonadotropin (anti-hCG) were incorporated into matrices of poly(ethylene-co-vinyl acetate), which is stable in biological environments. Human Ab and bovine gamma-globulin were also incorporated in biodegradable matrices of a poly-anhydride copolymer composed of a stearic acid dimer and sebacic acid. Abs were slowly released from all the polymeric carriers during 30 days of continuous immersion in buffered saline. The ability of anti-hCG to bind antigen was retained following release from EVAc matrices. Only minor Ab aggregation was observed following release from either polymer. Polymeric delivery systems, similar to those described here, may become an important element in the delivery of mAbs to humans for immunoprotection against infectious diseases or the delivery of mAb-conjugates for immunotherapy against cancer.

Stabilization of nerve growth factor in controlled release polymers and in tissue

“…Manipulation of the internal pore structure of a matrix, and hence the resistance to protein diffusion within the matrix [25], or the degradation rate of erodable polymers [26] can therefore yield release patterns persisting from a few days to a few years. Protein particle size and loading of polymer matrices affect both pore size and connectivity, and have been shown to affect release from both diffusion-controlled and erosion-controlled matrices [ 10,25,27,28]. Any species with which the protein of interest is codispersed also has the potential to affect protein diffusion and to control release rate [ 10,27].…”

Protein Delivery from Nondegradable Polymer Matrices

“…Macromolecules have been shown to retain their biological activity after release from EVAc. For example, a mAb against a human chorionic gonadatropin (hCG) retained its ability to bind to hCG after release from an EVAc matrix (Randomsky et al, 1992;Sherwood et al, 1992). In addition, when released from EVAc matrices, nerve growth factor stimulated neurite outgrowth in cultured cells (Powell et al, 1990), insulin altered the blood glucose levels in diabetic rats (Langer and Folkman, 1977;Brown et al, 1986), and angiogenesis inhibitors blocked new blood vessel growth (Lee and Langer, 1983).…”

“…EVAc matrix systems have been used to release a variety of macromolecules, such as polypeptide and protein hormones (Fischel-Ghodsian et al, 1988;Brown et al, 1986), heparin (Edelman et al, 1990), growth factors (Hoffman et al, 1990;Edelman et al, 1991;Murray et al, 1983;Powell et al, 1990;Beaty and Saltzman, 1992), inhibitors of tumor angiogenesis (Lee and Langer, 1983), polyclonal antibodies , monoclonal antibodies (mAb; Radomsky et al, 1992;Sherwood et al, 1992Sherwood et al, , 1996Saltzman et al, 1993), and antigens (Preis and Langer, 1979;Wyatt, 1994). Macromolecules have been shown to retain their biological activity after release from EVAc.…”

Novel Drug Delivery Systems for Posterior Segment Ocular Disease

“…Biodegradable polymers can also be used for protein delivery; often this can be achieved by adapting one of the methods developed for fabrication of EVAc protein delivery systems for use with a degradable polymer such as PLGA (101). Micro-and nanoparticulate systems from biodegradable polymers are particularly attractive for long-term protein delivery to the posterior segments of the eye.…”

“…Macromolecules retain their biological activity after release from EVAc. For example, MAbs against human chorionic gonadatropin (hCG) retained its ability to bind to hCG after release from an EVAc matrix (100,101) and MAbs that neutralize herpesvirus were effective after long-term delivery in animals (107) 7 . In addition, when released from EVAc matrices, nerve growth factor (NGF) stimulated neurite outgrowth in cultured cells (94), NGF enhanced choline acetyltransferase activity in neurons in the brain (108), insulin altered the blood glucose levels in diabetic rats (91), and angiogenesis inhibitors blocked new blood vessel growth (98).…”