Targeting the intestinal lymphatic system: a versatile path for enhanced oral bioavailability of drugs

ABSTRACT

Introduction: The major challenge of first pass metabolism in oral drug delivery can be surmounted by directing delivery toward intestinal lymphatic system (ILS). ILS circumvents the liver and transports drug directly into systemic circulation via thoracic duct. Lipid and polymeric nanoparticles are transported into ILS through lacteal and Peyer’s patches. Moreover, surface modification of nanoparticles with ligand which is specific for Peyer’s patches enhances the uptake of drugs into ILS. Bioavailability enhancement by lymphatic uptake is an advantageous approach adopted by scientists today. Therefore, it is important to understand clear insight of ILS in targeted drug delivery and challenges involved in it.

Areas covered: Current review includes an overview of ILS, factors governing lymphatic transport of nanoparticles and absorption mechanism of lipid and polymeric nanoparticles into ILS. Various ligands used to target Peyer’s patch and their conjugation strategies to nanoparticles are explained in detail. In vitro and in vivo models used to assess intestinal lymphatic transport of molecules are discussed further.

Expert opinion: Although ILS offers a versatile pathway for nanotechnology based targeted drug delivery, extensive investigations on validation of the lymphatic transport models and on the strategies for gastric protection of targeted nanocarriers have to be perceived in for excellent performance of ILS in oral drug delivery.

KEYWORDS:

• Intestinal lymphatic system
• oral delivery
• chylomicron
• Peyer’s patches
• nanoparticles
• EDC-NHS chemistry

Article Highlights

• ILS is one of the bioavailability enhancement pathways for drugs which undergo metabolism in the liver. However, unless selective uptake occurs in lymphatics, most of the drugs get metabolized before reaching to systemic circulation.

• Lipid nanoparticles are generally taken up into ILS through lacteal as chylomicron. Nanoparticles attached with targeting ligands can greatly enhance the uptake into ILS. However, protection from GIT environment is essential for intactness of targeted nanoparticles.

• For surface modification, nanoparticles can be functionalized with reactive group as described in this review for readily conjugation with ligands and proteins.

• Various in vitro and in vivo models are available for assessment of intestinal lymphatic transport. However, they lag behind in data reproducibility and are non-specific leading to misapprehension of the results.

• Therefore, an extensive investigation in validating the lymphatic transport models and strategies for gastric protection of targeted nanocarriers has to be perceived in future for excellent performance of ILS in oral drug delivery.

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Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties

Reviewer declaration of interest

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.