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Critical Reviews™ in Therapeutic Drug Carrier Systems
Импакт фактор: 2.9 5-летний Импакт фактор: 3.72 SJR: 0.736 SNIP: 0.551 CiteScore™: 2.43

ISSN Печать: 0743-4863
ISSN Онлайн: 2162-660X

Выпуски:
Том 36, 2019 Том 35, 2018 Том 34, 2017 Том 33, 2016 Том 32, 2015 Том 31, 2014 Том 30, 2013 Том 29, 2012 Том 28, 2011 Том 27, 2010 Том 26, 2009 Том 25, 2008 Том 24, 2007 Том 23, 2006 Том 22, 2005 Том 21, 2004 Том 20, 2003 Том 19, 2002 Том 18, 2001 Том 17, 2000 Том 16, 1999 Том 15, 1998 Том 14, 1997 Том 13, 1996 Том 12, 1995

Critical Reviews™ in Therapeutic Drug Carrier Systems

DOI: 10.1615/CritRevTherDrugCarrierSyst.v20.i23.30
62 pages

Emerging Trends in Oral Delivery of Peptide and Protein Drugs

Ram I. Mahato
Department of Pharmaceutical Sciences, University of Tennessee Health Science Center, 26 S. Dunlap Street, Feurt Building, Room 406, Memphis TN 38163, USA
Ajit S. Narang
Department of Pharmaceutical Sciences, University of Tennessee Health Science Center, Memphis, Tennessee, USA
Laura Thoma
Department of Pharmaceutical Sciences, University of Tennessee Health Science Center, Memphis, Tennessee, USA
Duane D. Miller
Department of Pharmaceutical Sciences, University of Tennessee Health Science Center, Memphis, Tennessee, USA

Краткое описание

Most peptide and protein drugs are currently used as parenteral formulations because of their poor oral bioavailability. Development of an effective oral delivery system for these macromolecular drugs requires a thorough understanding of their physicochemical properties, such as molecular weight, hydrophobicity, ionization constants, and pH stability, as well as biological barriers that restrict protein and peptide absorption from the gastrointestinal (GI) tract, including pH variability, enzymatic degradation, and membrane efflux. Various strategies currently under investigation include amino acid backbone modifications, formulation approaches, chemical conjugation of hydrophobic or targeting ligand, and use of enzyme inhibitors, mucoadhesive polymers, and absorption enhancers. However, there is only limited success because of the hostile environment of the GI tract-e.g., strong pH extremes and abundant presence of potent luminal enzymes. Th is review focuses on the challenges posed by the GI system and how different pharmaceutical approaches can be used to make oral delivery of protein and peptide drugs more feasible. Th e roles of P-glycoprotein and CYP3A4 in controlling the extent of intestinal absorption and metabolism will also be discussed.


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