Affordable Access

Publisher Website

Lipophilic prodrugs designed for intestinal lymphatic transport

Authors
Journal
Advanced Drug Delivery Reviews
0169-409X
Publisher
Elsevier
Publication Date
Volume
19
Issue
2
Identifiers
DOI: 10.1016/0169-409x(95)00105-g
Keywords
  • Low Molecular Weight Prodrugs
Disciplines
  • Biology
  • Chemistry
  • Design
  • Medicine

Abstract

Abstract The intestinal lymphatics are a specialised absorption and transport pathway for highly lipophilic drugs, lipids and lipidic derivatives, and lipophilic xenobiotics. Once a drug has gained access to the intestinal lymphatics (generally in association with specific lipoproteins formed by the enterocyte in response to co-administered lipid), it drains through the mesenteric lymphatics gaining access to the systemic circulation at the junction of the left internal jugular and left subclavian veins. Therefore, the major drug delivery opportunities associated with intestinal lymphatic transport of lipophilic prodrugs are the potential for (i) by-passing hepatic first pass metabolism after oral dosing, and (ii) targeting drugs to regions of the lymphatics. This review describes the necessary physicochemical and metabolic features of prodrugs designed for enhanced intestinal lymphatic transport. For lymphatic transport to be quantitatively important after oral administration, simple ester/ether approaches generally do not lead to significant lymphatic transport of the administered prodrug. Application of monoglyceride or triglyceride mimics, and more recently phospholipid mimics, appear to hold promise for selective lymphatic delivery. Examples of lipophilic prodrugs designed to avoid pre-systemic clearance, reduce gastrointestinal intolerance, and for targeting various disease states resident within the intestinal lymphatics are presented.

There are no comments yet on this publication. Be the first to share your thoughts.

Statistics

Seen <100 times
0 Comments

More articles like this

An experimental system designed to study the in si...

on International Journal of Pharm... Jan 01, 1986

Transport of lipophilic molecules by the intestina...

on Advanced Drug Delivery Reviews Jan 01, 1991

The in vitro transport of model thiodipeptide prod...

on Organic & Biomolecular Chemist... Sep 21, 2009

Evaluation of a chylomicron flow blocking approach...

on European Journal of Pharmaceut... March 2005
More articles like this..