Intestinal lymphatic transport for drug delivery

https://doi.org/10.1016/j.addr.2011.05.019Get rights and content

Abstract

Intestinal lymphatic transport has been shown to be an absorptive pathway following oral administration of lipids and an increasing number of lipophilic drugs, which once absorbed, diffuse across the intestinal enterocyte and while in transit associate with secretable enterocyte lipoproteins. The chylomicron-associated drug is then secreted from the enterocyte into the lymphatic circulation, rather than the portal circulation, thus avoiding the metabolically-active liver, but still ultimately returning to the systemic circulation. Because of this parallel and potentially alternative absorptive pathway, first-pass metabolism can be reduced while increasing lymphatic drug exposure, which opens the potential for novel therapeutic modalities and allows the implementation of lipid-based drug delivery systems. This review discusses the physiological features of the lymphatics, enterocyte uptake and metabolism, links between drug transport and lipid digestion/re-acylation, experimental model (in vivo, in vitro, and in silico) of lymphatic transport, and the design of lipid- or prodrug-based drug delivery systems for enhancing lymphatic drug transport.

Keywords

Drugs
Lymph
Absorption
Transport
Intestine
Formulation
Lipid
Oral
Delivery
Chylomicron

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This review is part of the Advanced Drug Delivery Reviews theme issue on “Lymphatic Drug Delivery: Therapy, Imaging and Nanotechnology”.

1

Current affiliation: Drug Metabolism and Pharmacokinetics, Alcon Research, Ltd., 6201 South Freeway, Mail Stop: R3-26, Forth Worth, TX 76134-2099, USA. Tel.: +1 817 568 7705; fax: +1 817 551 9854.

2

The authors contributed equally for the writing and editing of this manuscript.

3

Current affiliation: Drug Metabolism and Pharmacokinetics, Millennium Pharmaceuticals Inc., 35 Landsdowne St., Cambridge, MA 02139, USA.

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