Strategies for targeting protein therapeutics to selected tissues and cells.
The advent of recombinant biotechnology and the recent sequencing of the human genome now allow for identification of scores of potential protein therapeutics along with the capacity to produce them in quantities and purities required for clinical application. Thus, clinical development of potential protein therapeutics has become as commonplace as development efforts of classical small molecule therapeutics. Whereas small molecule therapeutic lead candidates are identified through screens of large sets of possibilities, therapeutic protein candidates are defined by genetic information as a single composition (or a limited set of isoforms). Small molecule leads are identified through the combined assessment of desired selectivity, biodistribution and pharmacokinetic properties. In essence, these selection parameters emulate the actions of protein therapeutics that function as systemic hormones through their ability to target selective cells and tissues of the body via selective receptor interaction with minimal actions elsewhere. However, many, if not most, potential protein therapeutics do not normally circulate through the body to reach their target cell or tissue; rather, they are frequently synthesised at local sites, act at that site and are degraded without reaching appreciable systemic levels. Dose-limiting adverse events are associated with systemic administration of many of these proteins, restricting their clinical potential. This review examines current strategies to reduce these dose-limiting events by possibly focusing the delivery of potential protein therapeutics to discrete tissues and cells.
Mrsny
Randall J
RJ
Welsh School of Pharmacy, Cardiff University, Cardiff, Wales, UK.
D000818:Animals; D001692:Biological Transport / Q000187:drug effects / Q000502:physiology; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D009928:Organ Specificity / Q000187:drug effects*; D011506:Proteins / Q000008:administration & dosage / Q000378:metabolism / Q000627:therapeutic use*
D011506:Proteins