Endogenous carriers and ligands in non-immunogenic site-specific drug delivery

Targeted drug delivery has gained recognition in modern therapeutics and attempts are being made to explore the potentials and possibilities of cell biology related bioevents in the development of specific, programmed and target oriented systems. The components which have been recognized to be tools include receptors and ligands, where the receptors act as molecular targets or portals, and ligands, with receptor specificity and selectivity, are trafficked en route to the target site. Although ligands of exogenous or synthetic origin contribute to the selectivity component of carrier constructs, they may impose immunological manifestations of different magnitudes. The latter may entail a continual quest for bio-compatible, non-immunogenic and target orientated delivery. Endogenous serum, cellular and extracellular bio-ligands interact with the colloidal carrier constructs and influence their bio-fate. However, these endogenous bio-ligands can themselves serve as targeting modules either in their native form or engineered as carrier cargo. Bio-regulatory, nutrient and immune ligands are sensitive, specific and effective site directing handles which add to targeted drug delivery. The present review provides an exhaustive account of the identified bio-ligands, which are not only non-immunogenic in nature but also site-specific. The cell-related bioevents which are instrumental in negotiating the uptake of bio-ligands are discussed. Further, a brief account of ligand-receptor interactions and the set of biological events which ensures ligand-driven trafficking of the ligand-receptor complex to the cellular interior is also presented. Since ligand-receptor interaction is a critical pre-requisite for negotiating cellular uptake of endogenous ligands and anchored carrier cargo, an attempt has been made to identify differential expression of receptors and bio-ligands under normal and etiological conditions. Studies which judiciously utilized bio-ligands or their analogs in negotiating site-specific drug delivery have been reviewed and presented. Targeted delivery of bioactives using endogenous bio-ligands offers enormous options and opportunities through carrier construct engineering and could become a future reality in clinical practice. (C) 2000 Elsevier Science B.V. All rights reserved.