An update on oral drug delivery via intestinal lymphatic transport

Abstract

Orally administered drug entities have to survive the harsh gastrointestinal environment, penetrate the enteric epithelia and circumvent hepatic metabolism before reaching the systemic circulation. Whereas the gastrointestinal stability can be well maintained by taking proper measures, hepatic metabolism presents as a formidable barrier to drugs suffering from first-pass metabolism. The pharmaceutical academia and industries are seeking alternative pathways for drug transport to circumvent problems associated with the portal pathway. Intestinal lymphatic transport is emerging as a promising pathway to this end. In this review, we intend to provide an updated overview on the rationale, strategies, factors and applications involved in intestinal lymphatic transport. There are mainly two pathways for peroral lymphatic transport-the chylomicron and the microfold cell pathways. The underlying mechanisms are being unraveled gradually and nowadays witness increasing research input and applications.

Keywords: ACQ, aggregation-caused quenching; ASRT, apical sodium-dependent bile acid transporter; AUC, area under curve; BCS, biopharmaceutics classification system; CM, chylomicron; Chylomicron; DC, dendritic cell; DDT, dichlorodiphenyltrichloroethane; DTX, docetaxel; Drug absorption; Drug carriers; Drug delivery; FA, fatty acid; FAE, follicle-associated epithelia; FRET, Föster resonance energy transfer; GIT, gastrointestinal tract; HBsAg, hepatitis B surface antigen; HIV, human immunodeficiency virus; LDL, low-density lipoprotein; LDV, Leu-Asp-Val; LDVp, LDV peptidomimetic; Lymphatic transport; M cell, microfold cells; MG, monoglyceride; MPA, mycophenolic acid; MPS, mononuclear phagocyte system; Microfold cell; Nanoparticles; OA, oleate; Oral; PCL, polycaprolactone; PEG-PLA, polyethylene glycol-poly(lactic acid); PEI, polyethyleneimine; PLGA, poly(lactic-co-glycolic acid); PVA, poly(vinyl alcohol); RGD, Arg-Gly-Asp; RGDp, RGD peptidomimetic; SEDDS, self-emulsifying drug delivery system; SLN, solid lipid nanoparticles; SNEDDS, self-nanoemulsifying drug delivery system; TEM, transmission electron microscopy; TG, triglyceride; TPGS, D-α-tocopherol polyethylene glycol 1000 succinate; TU, testosterone undecanoate; WGA, wheat germ agglutinin; YCW, yeast cell wall.