Lymphatic Delivery and Targeting of Drugs, Vaccines, and Imaging Agents

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About this Research Topic

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Background

As a network largely in parallel to the blood vasculature, the lymphatic system is an integral part of the vascular system that facilitate transportation of nutrients and information exchange in the body. The lymphatic system performs key physiological functions including fluid balance, nutrition absorption and maintenance of immune homeostasis. To highlight the last point particularly: the lymphatic networks, including vessels, nodes, and other lymphoid tissues, are the essential sites for immune cell transport, activation and proliferation (up to 95% of the immune cells in the body are contained within the lymphatics at any one time compared to less than 5% in the blood). Malfunction of the lymphatic system, in turn, is commonly seen in a large number of immune-related diseases. The unique features of the lymphatic system provide an interface to efficiently modulate the immune system via targeted drug delivery. Such delivery approaches can potentially improve the treatment of a large number of diseases, realizing the involvements of immune ‘elements’ in many pathophysiological conditions, such as autoimmune and inflammatory disorders, cancer metastasis, infectious diseases, and metabolic syndrome. In addition, lymphatics also plays a critical role in mounting immune reactions following vaccination, and therefore the efficacy of vaccines would also benefit from delivery systems having optimal dynamic interaction with the lymphatics.

There have been increasing numbers of publications and drug development programs demonstrating enhanced treatment due to targeted delivery into or via the lymphatic system, including delivery of small or macro molecular therapeutics or diagnostic agents, as well as vaccines. The current Research Topic aims to provide a timely overview and updates in the field of lymphatic drug delivery. The selections include review articles to introduce fundamental principles that dictate the transport of therapeutics and other molecules via the lymphatics. A number of research articles/communications will be also included to demonstrate the utility of lymphatic drug delivery in promoting efficacy via different mechanisms: for example, co-localisation of high concentrations of drugs and their designated targets in the relatively confined lymphatic compartment may result in sufficiently pharmacological activity even when the drugs are administered at low doses; alternatively, ‘unprecedented’ exposure of theranostic systems to the lymphatics may enable unique treatment outcomes that would not have been anticipated as a result of conventional drug delivery routes (e.g. via the blood stream). Comments and Methods are also expected for this topical selection to facilitate discussion and research collaborations in this field.

For this Research Topic, we invite authors to submit Research, Mini-Reviews, Protocols, and Perspective articles that showcase basic or translational aspects in the field of lymphatic transport or targeting of small molecule drugs, protein/peptides, vaccines, vehicles for gene/cell therapies or endogenous macromolecular/cellular components. We welcome studies that provide scientific or translational updates on the following subtopics, but not limited to:

- Delivery systems to enhance lymphatic targeting of small molecule drugs, which results in better PK/PD outcomes for treatment of immune disorders, cancers or other diseases.

- Design or modification of macromolecule drugs to improve delivery outcomes, such as optimal absorption from (non-IV) injection sites and higher stability during transition via the lymphatics.

- Lymph-directing imaging agents or delivery systems for imaging agents that facilitate disease diagnosis or provide novel tools for fundamental medical research.

- Carriers or adjuvants for vaccine delivery that facilitate interaction with immunological components in the lymphatic system.

- Therapeutic strategies targeting lymphatics in the tumor-microenvironments, or other ‘immune interfaces’ that mediate pathologies relevant to gut-liver/gut-brain axis, and metabolic syndrome.

- In vitro or in vivo models that facilitate preclinical studies, or clinical studies that show lymphatic drug transport or proof-of-concept utility of the lymphatic drug delivery approach in humans.

- Replication of virus (e.g. HIV) or other pathogens in the lymphatic system and drug delivery strategies that may benefit anti-viral or anti-infective efficacy.

- Mathematical modeling of lymphatic drug delivery and targeting. We welcome only mathematical modeling contributions that have novelty in the modeling approach and/or a translational (wet lab) test of the model.

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The Topic Editor Pavel Gershkovich received financial support from AstraZeneca, Rosetrees Trust and EPSRC for research related to lymphatic transport of drugs.
The Topic Editor Leonid Kagan received financial support from Bristol Myers Squibb for research of lymphatic drug absorption.
The Topic Editors Sifei Han and Natalie Trevaskis are inventors of the lymph-directing glyceride prodrug technology that has been patented and licensed via a commercial agreement with PureTech Health, Boston. PureTech Health has subsequently entered into a collaboration agreement with Boehringer Ingelheim to explore the technology in immune modulation.

Keywords: lymphatic system, drug delivery, immunotherapy, lymphatic transport, autoimmune diseases, vaccine, tumor micro-environment

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

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