The role of lymphatic transport in enhancing oral protein and peptide drug delivery.
The gastrointestinal lymphatic system is a specific transport pathway through which dietary lipids, fat-soluble vitamins, and water-insoluble peptide-type molecules (e.g., cyclosporine A) can gain access to the systemic circulation. Drugs transported by way of the gastrointestinal lymphatic system bypass the liver and avoid potential hepatic first-pass metabolism. Lymphatic delivery of immunomodulatory and low therapeutic index protein and peptide drugs used in the treatment of cancer cell metastases and HIV presents an opportunity to maximize therapeutic benefit while minimizing general systemic drug exposure. Furthermore, lymphatic drug transport may promote drug incorporation into the body's lipid-handling system, thus offering the potential to manipulate drug distribution and residence time within the body. This review article will discuss the potential utilization of lymphatic transport in enhancing the oral absorption of protein- and peptide-like drugs.
Wasan
Kishor M
KM
Division of Pharmaceutics and Biopharmaceutics, Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, British Columbia, Canada V6T 1Z3. kwasan@interchange.ubc.ca
D000284:Administration, Oral; D000818:Animals; D001692:Biological Transport; D004064:Digestive System / Q000378:metabolism*; D016503:Drug Delivery Systems; D006801:Humans; D007408:Intestinal Absorption; D050356:Lipid Metabolism; D008055:Lipids / Q000008:administration & dosage / Q000493:pharmacokinetics; D008208:Lymphatic System / Q000378:metabolism*; D010455:Peptides / Q000008:administration & dosage / Q000378:metabolism* / Q000493:pharmacokinetics; D004364:Pharmaceutical Preparations / Q000008:administration & dosage* / Q000378:metabolism; D011506:Proteins / Q000008:administration & dosage / Q000378:metabolism* / Q000493:pharmacokinetics; D012995:Solubility
D008055:Lipids; D010455:Peptides; D004364:Pharmaceutical Preparations; D011506:Proteins