Albumin shuttling effects of synthetic substances bearing albumin binding moieties

Abstract

Albumin shuttling effect is a unique property of albumin in living body which can transport various materials including small molecular weight drugs. Moreover, albumin has a long half-life of 19 days in human and a tendency of accumulation on pathogenic sites. With attractive properties of albumin, albumin has been used as drug carrier in drug delivery systems to improve pharmacokinetic profile of small molecular weight drug and delivery efficiency into pathogenic sites. Most of exogenous albumin based drugs showed high therapeutic efficiency in clinical filed. However, exogenous albumin based drug delivery systems have a risk of immunogenicity from pathogenic substances as well as a cost and difficulty to have well-defined structure in manufacturing perspective. Therefore, attaching albumin binding ligands with a drug to make a complex with endogenous albumin has been focused for the new drug delivery strategy. Herein, this study focused on albumin shuttling effect using endogenous albumin by Cy5.5 conjugated three binding moieties: albumin binding peptide, long chain fatty acid, and maleimide group. The in vitro complexation patterns, conformation change, affinity, cellular uptakes, in vivo pharmacokinetic profiles, and biodistribution in tumor bearing mouse were analyzed. Three albumin binding moieties, especially long chain fatty acid was observed as significant potential to attach to anti-cancer drug. The sufficient potential of endogenous albumin with three binding moieties as drug carrier was validated and this may provide insight of endogenous albumin shuttling effect for tumor target-specific nano-medicine.