Expert opinion on drug delivery · 2014
Albumin and its application in drug delivery.
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Sleep Darrell
Аннотация
INTRODUCTION: Rapid clearance of drugs from the body results in short therapeutic half-life and is an integral property of many protein and peptide-based drugs. To maintain the desired therapeutic effect patients are required to administer higher doses more frequently, which is inconvenient and risks undesirable side effects. Drug delivery technologies aim to minimise the number of administrations and dose-related toxicity while maximising therapeutic efficacy.
AREAS COVERED: This review describes albumin's inherent biochemical and biophysical properties, which make it an attractive drug delivery platform and the developmental status of drugs that are associated, conjugated or genetically fused with albumin. Albumin interacts with a number of cell surface receptors including gp18, gp30, gp60, FcRn, cubilin and megalin. The importance of albumin's interaction with the FcRn receptor, the basis for albumin's long circulatory half-life, is described, as are engineered albumins with improved pharmacokinetics. Albumin naturally accumulates at tumours and sites of inflammation, a characteristic which can be augmented by the addition of targeting ligands. The development of albumin drug conjugates which reply upon this property is described.
EXPERT OPINION: Albumin's inherent biochemical and biophysical properties make it an ideal drug delivery platform. Recent advances in our understanding of albumin physiology and the improvement in albumin-based therapies strongly suggest that albumin-based therapies have a significant advantage over alternative technologies in terms of half-life, stability, versatility, safety and ease of manufacture. Given the importance of the albumin:FcRn interaction, the interpretation of the pharmacokinetic and pharmacodynamic profiles of albumin-based therapeutics with disturbed albumin:FcRn interaction may have to be reassessed. The FcRn receptor has additional functionality, especially in relation to immunology, antigen presentation and delivery of proteins across mucosal membranes, consequently albumin-based fusions and conjugates may have a future role in oral and pulmonary-based vaccines and drug delivery.
AREAS COVERED: This review describes albumin's inherent biochemical and biophysical properties, which make it an attractive drug delivery platform and the developmental status of drugs that are associated, conjugated or genetically fused with albumin. Albumin interacts with a number of cell surface receptors including gp18, gp30, gp60, FcRn, cubilin and megalin. The importance of albumin's interaction with the FcRn receptor, the basis for albumin's long circulatory half-life, is described, as are engineered albumins with improved pharmacokinetics. Albumin naturally accumulates at tumours and sites of inflammation, a characteristic which can be augmented by the addition of targeting ligands. The development of albumin drug conjugates which reply upon this property is described.
EXPERT OPINION: Albumin's inherent biochemical and biophysical properties make it an ideal drug delivery platform. Recent advances in our understanding of albumin physiology and the improvement in albumin-based therapies strongly suggest that albumin-based therapies have a significant advantage over alternative technologies in terms of half-life, stability, versatility, safety and ease of manufacture. Given the importance of the albumin:FcRn interaction, the interpretation of the pharmacokinetic and pharmacodynamic profiles of albumin-based therapeutics with disturbed albumin:FcRn interaction may have to be reassessed. The FcRn receptor has additional functionality, especially in relation to immunology, antigen presentation and delivery of proteins across mucosal membranes, consequently albumin-based fusions and conjugates may have a future role in oral and pulmonary-based vaccines and drug delivery.