Albumin-based drug delivery

The therapeutic efficacy of a drug is determined by the ability for site-specific engagement with its biological target. A poor pharmacokinetic profile as a result of degradation, rapid renal clearance or nonspecific accumulation requires enabling technologies provided by delivery science. Two major delivery branches are plasma half-life extension for improved stability and prolonged plasma residence time for long-acting extracellular drugs, and targeted intracellular drug-delivery to maximize organ-specific or intracellular drug-delivery. Human serum albumin (HSA) may provide the solution to this unmet challenge by exploitation of its properties albumin is an attractive candidate for half-life extension and targeted intracellular delivery of drugs attached by association or ligand-mediated association (A), genetic fusions (B) or covalent conjugation (C).

Albumin is a natural carrier protein possessing multiple ligand binding sites and a plasma half-life of approximately 20 days facilitated by engagement with the endothelial and epithelial cellular recycling neonatal Fc receptor (FcRn), and megalin-cubilin receptor-mediated renal rescue affording a broad biodistribution and tissue penetration in normal and disease conditions. Utilization of its physiological transport mechanisms and its high charge and solubility properties, promotes albumin as a highly attractive technology that can be utilized for both half-life extension and targeted intracellular delivery applications.

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