Albumin-based drug designs for pharmacokinetic modulation.
INTRODUCTION
A poor pharmacokinetic profile due to inadequate distribution and rapid renal clearance limits site-specific target engagement and drug efficacy. The inherent properties of human serum albumin for broad tissue distribution, prolonged circulation, and ligand transport have been engineered into albumin-based drug designs to modulate the pharmacokinetics to increase efficacy and reduce the frequency of dose.


AREAS COVERED
This review highlights albumin structural features, ligand binding, and molecular interactions key to albumin-drug designs and an overview of the repertoire of albumin-drugs and approaches, with focus on pharmacokinetics of marketed products and clinical trials.


EXPERT OPINION
Comparison, and advantages as well as disadvantages of the endogenous albumin-binding versus recombinant albumin construct approach, and half-life extension and intracellular drug delivery applications. The section addresses current challenges and solutions to the different drug designs, and considerations needed to progress the field such as conjugation chemistries, drug loading, and animal models. The section highlights the need for a paradigm shift in the field from 'utilizing' to 'controlling' albumin transport with recombinant human albumin variants engineered for tuned affinity to albumin cellular receptors.
['Pilati|Diego|D|', 'Howard|Kenneth A|KA|']
D000818:Animals D016503:Drug Delivery Systems D015195:Drug Design D006801:Humans D004364:Pharmaceutical Preparations D010599:Pharmacokinetics D000075462:Serum Albumin, Human D014018:Tissue Distribution
pharmacokinetics Human serum albumin half-life extension drug delivery recombinant human albumin albumin domains albumin fusions biomolecular assemblies drug conjugation long-acting drugs neonatal Fc receptor (FcRn)