Pharmaceutical stratégies utilizing recombinant human serum albumin

• Published in: Pharmaceutical research 2002-05, Vol.19 (5), p.569-577
• Main Authors: TUAN GIAM CHUANG, Victor, KRAGH-HANSEN, Ulrich, OTAGIRI, Masaki
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Biological Transport; Biotechnology industry; Blood & organ donations; Blood Substitutes - chemistry; Blood Substitutes - pharmacokinetics; Blood-brain barrier; Blood-Brain Barrier - physiology; Carbon; Drug Carriers; Drug delivery systems; General pharmacology; Genetic Vectors; Glucose; Humans; Insulin - chemistry; Insulin - pharmacokinetics; Medical sciences; Microspheres; Mutation; Pharmaceutical industry; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Plasma; Protein Binding; Proteins; Recombinant Proteins - biosynthesis; Recombinant Proteins - chemistry; Serum Albumin - biosynthesis; Serum Albumin - chemistry; Serum Albumin - genetics; Ultrasonic imaging; Yeast
• ISSN: 0724-8741; 1573-904X

Gene manipulation techniques open up the possibility of making recombinant human serum albumin (rHSA) or mutants with desirable therapeutic properties and for protein fusion products. rHSA can serve as a carrier in synthetic heme protein, thus reversibly carrying oxygen. Myristoylation of insulin results in a prolonged half-life because of self aggregation and increased albumin binding. Preferential albumin uptake by tumor cells serves as the basis for albumin-anticancer drug conjugate formulation. Furthermore, drug targeting can be achieved by incorporating drugs into albumin microspheres whereas liver targeting can be achieved by conjugating drug with galactosylated or mannosylated albumin. Microspheres and nanoparticles of different sizes can, with or without drugs and/or radioisotopes, be used for drug delivery or diagnostic purposes. In vivo implantation of albumin fusion protein expressing cells encapsulated in HSA-alginate coated beads showed promising results compared to organoids in rats. Chimeric peptide strategy with cationized albumin as the transport can deliver drugs via receptor mediated transcytosis through the blood brain barrier. Gene bearing, albumin microbubbles containing ultrasound contrast agents can non-invasively deliver gene after destruction by ultrasound. Various site-directed mutants of HSA can be tailor made depending on the application required.