ABSTRACT
Protein and peptide drugs possess many advantages over their small-molecule counterparts: they have a relatively high speci›city and low toxicity as well as unique mechanisms of action. The value of antibodies in ocular therapy is clearly evident in the clinical success of Lucentis for treating wet age-related macular degeneration (AMD). Antibodies, antibody fragments, and proteins are showing promise in clinical and preclinical stages of development for treating a wide variety of ophthalmic conditions (Tables 10.1 and 10.2). Obviously, proteins represent a valuable class of therapeutic agents for the eye. However, the clinical application of protein and peptide drug substances is limited due to poor bioavailability and disposition. Protein molecules are often hydrophilic large molecules, impermeable to most membranes, and have poor systemic absorption. Intravenous and subcutaneous delivery is the most common route of administration for protein drugs. Direct intravenous administration of protein therapeutics mitigates the issues of poor bioavailability; however, proteins often suffer from short plasma half-lives and poor penetration into the target tissues. This results in a requirement for frequent high-dose administrations often leading to poor compliance and potential toxic side effects.
