Controlled-release and local delivery of therapeutic antibodies.
Human and humanised antibodies are now poised to become a major new class of protein-based therapeutic agents. A significant fraction of new drugs in clinical testing (approximately 20% in 2002) are antibody classes. Monoclonal antibodies (mAbs) with high affinities against newly discovered disease targets, both cellularly and extracellularly, are now clinically proven to elicit high bioactivities against numerous diseases, including tumours, infections, asthma, inflammation, arthritis and osteoporosis. Clinical humanised antibody delivery is typically intravenous, with large multiple doses (grams) required for systemic volumes of distribution. Due to the relatively high costs of both this drug type, and its common mode of administration, alternatives are sought where doses might be reduced and the bioavailability and efficacy enhanced. Local, controlled-release methods that deliver antibodies locally to site of disease, offer new possibilities with these potential advantages. However, protein drugs frequently exhibit formulation challenges when packaged in delivery vehicles, and as globular proteins, antibodies are no exception. Several examples of mAb controlled-release and local delivery strategies against several disease targets are reviewed. Importantly, several antibody delivery methods work in tandem with existing clinically-accepted therapeutics, sometimes exhibiting potentiating or synergistic effects in animal models with small molecule, systemically administered drugs.
Department of Chemistry, Colorado State University, Fort Collins, CO 80523-1872, USA. david.grainger@colostate.edu.
David W
DW
Grainger
D000336:Aerosols; D000818:Animals; D000906:Antibodies / Q000008:administration & dosage* / Q000191:economics / Q000276:immunology / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000627:therapeutic use; D000937:Antigen-Antibody Reactions; D002986:Clinical Trials as Topic; D003692:Delayed-Action Preparations; D004333:Drug Administration Routes; D016527:Drug Costs; D016503:Drug Delivery Systems / Q000379:methods*; D004343:Drug Implants; D006801:Humans; D007116:Immunization, Passive; D016756:Immunoglobulins, Intravenous / Q000008:administration & dosage / Q000627:therapeutic use; D007167:Immunotherapy; D051379:Mice; D011487:Protein Conformation; D015202:Protein Engineering; D013329:Structure-Activity Relationship
D000336:Aerosols; D000906:Antibodies; D000911:Antibodies, Monoclonal; D003692:Delayed-Action Preparations; D004343:Drug Implants; D016756:Immunoglobulins, Intravenous