Intestinal Lymphatic Biology, Drug Delivery, and Therapeutics: Current Status and Future Directions.

Autor:	Reddiar SB; Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia (S.B.R., Y.X., M.A., S.H., L.H., O.M.F., G.G., A.A., Z.L., M.A.F., I.K.S., C.J.H.P., E.C., N.L.T.); China Pharmaceutical University, Nanjing, China (S.H., L.H.); Applied Surgery and Metabolism Laboratory, School of Biological Sciences (A.R.J.P.) and Surgical and Translational Research Centre, Department of Surgery, Faculty of Medical and Health Sciences (A.R.J.P., J.A.W.), University of Auckland, Auckland, New Zealand; and Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia (N.L.T.)., Xie Y; Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia (S.B.R., Y.X., M.A., S.H., L.H., O.M.F., G.G., A.A., Z.L., M.A.F., I.K.S., C.J.H.P., E.C., N.L.T.); China Pharmaceutical University, Nanjing, China (S.H., L.H.); Applied Surgery and Metabolism Laboratory, School of Biological Sciences (A.R.J.P.) and Surgical and Translational Research Centre, Department of Surgery, Faculty of Medical and Health Sciences (A.R.J.P., J.A.W.), University of Auckland, Auckland, New Zealand; and Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia (N.L.T.)., Abdallah M; Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia (S.B.R., Y.X., M.A., S.H., L.H., O.M.F., G.G., A.A., Z.L., M.A.F., I.K.S., C.J.H.P., E.C., N.L.T.); China Pharmaceutical University, Nanjing, China (S.H., L.H.); Applied Surgery and Metabolism Laboratory, School of Biological Sciences (A.R.J.P.) and Surgical and Translational Research Centre, Department of Surgery, Faculty of Medical and Health Sciences (A.R.J.P., J.A.W.), University of Auckland, Auckland, New Zealand; and Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia (N.L.T.)., Han S; Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia (S.B.R., Y.X., M.A., S.H., L.H., O.M.F., G.G., A.A., Z.L., M.A.F., I.K.S., C.J.H.P., E.C., N.L.T.); China Pharmaceutical University, Nanjing, China (S.H., L.H.); Applied Surgery and Metabolism Laboratory, School of Biological Sciences (A.R.J.P.) and Surgical and Translational Research Centre, Department of Surgery, Faculty of Medical and Health Sciences (A.R.J.P., J.A.W.), University of Auckland, Auckland, New Zealand; and Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia (N.L.T.)., Hu L; Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia (S.B.R., Y.X., M.A., S.H., L.H., O.M.F., G.G., A.A., Z.L., M.A.F., I.K.S., C.J.H.P., E.C., N.L.T.); China Pharmaceutical University, Nanjing, China (S.H., L.H.); Applied Surgery and Metabolism Laboratory, School of Biological Sciences (A.R.J.P.) and Surgical and Translational Research Centre, Department of Surgery, Faculty of Medical and Health Sciences (A.R.J.P., J.A.W.), University of Auckland, Auckland, New Zealand; and Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia (N.L.T.)., Feeney OM; Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia (S.B.R., Y.X., M.A., S.H., L.H., O.M.F., G.G., A.A., Z.L., M.A.F., I.K.S., C.J.H.P., E.C., N.L.T.); China Pharmaceutical University, Nanjing, China (S.H., L.H.); Applied Surgery and Metabolism Laboratory, School of Biological Sciences (A.R.J.P.) and Surgical and Translational Research Centre, Department of Surgery, Faculty of Medical and Health Sciences (A.R.J.P., J.A.W.), University of Auckland, Auckland, New Zealand; and Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia (N.L.T.)., Gracia G; Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia (S.B.R., Y.X., M.A., S.H., L.H., O.M.F., G.G., A.A., Z.L., M.A.F., I.K.S., C.J.H.P., E.C., N.L.T.); China Pharmaceutical University, Nanjing, China (S.H., L.H.); Applied Surgery and Metabolism Laboratory, School of Biological Sciences (A.R.J.P.) and Surgical and Translational Research Centre, Department of Surgery, Faculty of Medical and Health Sciences (A.R.J.P., J.A.W.), University of Auckland, Auckland, New Zealand; and Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia (N.L.T.)., Anshabo A; Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia (S.B.R., Y.X., M.A., S.H., L.H., O.M.F., G.G., A.A., Z.L., M.A.F., I.K.S., C.J.H.P., E.C., N.L.T.); China Pharmaceutical University, Nanjing, China (S.H., L.H.); Applied Surgery and Metabolism Laboratory, School of Biological Sciences (A.R.J.P.) and Surgical and Translational Research Centre, Department of Surgery, Faculty of Medical and Health Sciences (A.R.J.P., J.A.W.), University of Auckland, Auckland, New Zealand; and Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia (N.L.T.)., Lu Z; Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia (S.B.R., Y.X., M.A., S.H., L.H., O.M.F., G.G., A.A., Z.L., M.A.F., I.K.S., C.J.H.P., E.C., N.L.T.); China Pharmaceutical University, Nanjing, China (S.H., L.H.); Applied Surgery and Metabolism Laboratory, School of Biological Sciences (A.R.J.P.) and Surgical and Translational Research Centre, Department of Surgery, Faculty of Medical and Health Sciences (A.R.J.P., J.A.W.), University of Auckland, Auckland, New Zealand; and Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia (N.L.T.)., Farooq MA; Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia (S.B.R., Y.X., M.A., S.H., L.H., O.M.F., G.G., A.A., Z.L., M.A.F., I.K.S., C.J.H.P., E.C., N.L.T.); China Pharmaceutical University, Nanjing, China (S.H., L.H.); Applied Surgery and Metabolism Laboratory, School of Biological Sciences (A.R.J.P.) and Surgical and Translational Research Centre, Department of Surgery, Faculty of Medical and Health Sciences (A.R.J.P., J.A.W.), University of Auckland, Auckland, New Zealand; and Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia (N.L.T.)., Styles IK; Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia (S.B.R., Y.X., M.A., S.H., L.H., O.M.F., G.G., A.A., Z.L., M.A.F., I.K.S., C.J.H.P., E.C., N.L.T.); China Pharmaceutical University, Nanjing, China (S.H., L.H.); Applied Surgery and Metabolism Laboratory, School of Biological Sciences (A.R.J.P.) and Surgical and Translational Research Centre, Department of Surgery, Faculty of Medical and Health Sciences (A.R.J.P., J.A.W.), University of Auckland, Auckland, New Zealand; and Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia (N.L.T.)., Phillips ARJ; Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia (S.B.R., Y.X., M.A., S.H., L.H., O.M.F., G.G., A.A., Z.L., M.A.F., I.K.S., C.J.H.P., E.C., N.L.T.); China Pharmaceutical University, Nanjing, China (S.H., L.H.); Applied Surgery and Metabolism Laboratory, School of Biological Sciences (A.R.J.P.) and Surgical and Translational Research Centre, Department of Surgery, Faculty of Medical and Health Sciences (A.R.J.P., J.A.W.), University of Auckland, Auckland, New Zealand; and Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia (N.L.T.)., Windsor JA; Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia (S.B.R., Y.X., M.A., S.H., L.H., O.M.F., G.G., A.A., Z.L., M.A.F., I.K.S., C.J.H.P., E.C., N.L.T.); China Pharmaceutical University, Nanjing, China (S.H., L.H.); Applied Surgery and Metabolism Laboratory, School of Biological Sciences (A.R.J.P.) and Surgical and Translational Research Centre, Department of Surgery, Faculty of Medical and Health Sciences (A.R.J.P., J.A.W.), University of Auckland, Auckland, New Zealand; and Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia (N.L.T.)., Porter CJH; Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia (S.B.R., Y.X., M.A., S.H., L.H., O.M.F., G.G., A.A., Z.L., M.A.F., I.K.S., C.J.H.P., E.C., N.L.T.); China Pharmaceutical University, Nanjing, China (S.H., L.H.); Applied Surgery and Metabolism Laboratory, School of Biological Sciences (A.R.J.P.) and Surgical and Translational Research Centre, Department of Surgery, Faculty of Medical and Health Sciences (A.R.J.P., J.A.W.), University of Auckland, Auckland, New Zealand; and Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia (N.L.T.)., Cao E; Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia (S.B.R., Y.X., M.A., S.H., L.H., O.M.F., G.G., A.A., Z.L., M.A.F., I.K.S., C.J.H.P., E.C., N.L.T.); China Pharmaceutical University, Nanjing, China (S.H., L.H.); Applied Surgery and Metabolism Laboratory, School of Biological Sciences (A.R.J.P.) and Surgical and Translational Research Centre, Department of Surgery, Faculty of Medical and Health Sciences (A.R.J.P., J.A.W.), University of Auckland, Auckland, New Zealand; and Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia (N.L.T.)., Trevaskis NL; Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia (S.B.R., Y.X., M.A., S.H., L.H., O.M.F., G.G., A.A., Z.L., M.A.F., I.K.S., C.J.H.P., E.C., N.L.T.); China Pharmaceutical University, Nanjing, China (S.H., L.H.); Applied Surgery and Metabolism Laboratory, School of Biological Sciences (A.R.J.P.) and Surgical and Translational Research Centre, Department of Surgery, Faculty of Medical and Health Sciences (A.R.J.P., J.A.W.), University of Auckland, Auckland, New Zealand; and Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia (N.L.T.).
Jazyk:	angličtina
Zdroj:	Pharmacological reviews [Pharmacol Rev] 2024 Oct 16; Vol. 76 (6), pp. 1326-1398. Date of Electronic Publication: 2024 Oct 16.
DOI:	10.1124/pharmrev.123.001159
Abstrakt:	Historically, the intestinal lymphatics were considered passive conduits for fluids, immune cells, dietary lipids, lipid soluble vitamins, and lipophilic drugs. Studies of intestinal lymphatic drug delivery in the late 20th century focused primarily on the drugs' physicochemical properties, especially high lipophilicity, that resulted in intestinal lymphatic transport. More recent discoveries have changed our traditional view by demonstrating that the lymphatics are active, plastic, and tissue-specific players in a range of biological and pathological processes, including within the intestine. These findings have, in turn, inspired exploration of lymph-specific therapies for a range of diseases, as well as the development of more sophisticated strategies to actively deliver drugs or vaccines to the intestinal lymph, including a range of nanotechnologies, lipid prodrugs, and lipid-conjugated materials that "hitchhike" onto lymphatic transport pathways. With the increasing development of novel therapeutics such as biologics, there has been interest in whether these therapeutics are absorbed and transported through intestinal lymph after oral administration. Here we review the current state of understanding of the anatomy and physiology of the gastrointestinal lymphatic system in health and disease, with a focus on aspects relevant to drug delivery. We summarize the current state-of-the-art approaches to deliver drugs and quantify their uptake into the intestinal lymphatic system. Finally, and excitingly, we discuss recent examples of significant pharmacokinetic and therapeutic benefits achieved via intestinal lymphatic drug delivery. We also propose approaches to advance the development and clinical application of intestinal lymphatic delivery strategies in the future. SIGNIFICANCE STATEMENT: This comprehensive review details the understanding of the anatomy and physiology of the intestinal lymphatic system in health and disease, with a focus on aspects relevant to drug delivery. It highlights current state-of-the-art approaches to deliver drugs to the intestinal lymphatics and the shift toward the use of these strategies to achieve pharmacokinetic and therapeutic benefits for patients. (Copyright © 2024 by The American Society for Pharmacology and Experimental Therapeutics.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu