Targeted oral delivery of a drug via the intestinal lymphatic system (ILS) has the advantages of protecting against hepatic first-pass metabolism of the drug and improving its pharmacokinetic performance. It is also a promising route for the oral delivery of vaccines and therapeutic agents to induce mucosal immune responses and treat lymphatic diseases, respectively. This article describes the anatomical structures and physiological characteristics of the ILS, with an emphasis on enterocytes and microfold (M) cells, which are the main gateways for the transport of particulate delivery vehicles across the intestinal epithelium into the lymphatics. A comprehensive overview of recent advances in the rational engineering of particulate vehicles, along with the challenges and opportunities that they present for improving ILS drug delivery, is provided, and the mechanisms by which such vehicles target and transport through enterocytes or M cells are discussed. The use of naturally sourced materials, such as yeast microcapsules and their derived polymeric β-glucans, as novel ILS-targeting delivery vehicles is also reviewed. Such use is the focus of an emerging field of research. Their potential use in the oral delivery of nucleic acids, such as mRNA vaccines, is proposed.

Engineering Nano- and Microparticles as Oral Delivery Vehicles to Promote Intestinal Lymphatic Drug Transport.

Bioavailability enhancement of vitamin E TPGS liposomes of nintedanib esylate: formulation optimization, cytotoxicity and pharmacokinetic studies

Ligand-modified nanocarriers for oral drug delivery: Challenges, rational design, and applications.

The lymphatic system has grasped attention of researchers to a greater extent. The conventional methods of lymphatic delivery are now being modified to include nanotechnology to enhance the targeting of the drug at the specific pathological site. Scientists have worked successfully on different drug loaded nanocarriers that are modulated for the lymphatic system targeting for the treatment of various fatal diseases. Huge strides have been made in methods of delivery of these drugs either individually or in combination along with nanoparticles, therapeutic genes, and vaccines. However, the products introduced for commercial use are almost near nil. Altogether, there are challenges that need to be resolved and studies that are meant to be done for further improvements. The current review focuses on the understanding and pathophysiology of the lymphatic system and changes that occur during disease, drug characteristics, and physicochemical parameters that influence the lymphatic uptake of drugs and different nanocarriers. We further highlight different potential results obtained over the years with nanocarriers and other delivery methods to effectively target the lymphatic system for their therapeutic application. The challenges and drawbacks governing the lack of products available clinically have also been discussed. 

Lymphatic targeting for therapeutic application using nanoparticulate systems

Abstract The lymphatic system has grasped attention of researchers to a greater extent. The conventional methods of lymphatic delivery are now being modified to include nanotechnology to enhance the targeting of the drug at the specific pathological site. Scientists have worked successfully on different drug loaded nanocarriers that are modulated for the lymphatic system targeting for the treatment of various fatal diseases. Huge strides have been made in methods of delivery of these drugs either individually or in combination along with nanoparticles, therapeutic genes, and vaccines. However, the products introduced for commercial use are almost near nil. Altogether, there are challenges that need to be resolved and studies that are meant to be done for further improvements. The current review focuses on the understanding and pathophysiology of the lymphatic system and changes that occur during disease, drug characteristics, and physicochemical parameters that influence the lymphatic uptake of drugs and different nanocarriers. We further highlight different potential results obtained over the years with nanocarriers and other delivery methods to effectively target the lymphatic system for their therapeutic application. The challenges and drawbacks governing the lack of products available clinically have also been discussed.

Priyanka Pandya

Papers

Nanocarriers based oral lymphatic drug targeting: Strategic bioavailability enhancement approaches