Recent Approaches for Lymphatic Drug Delivery

A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Drug Delivery and Controlled Release".

Deadline for manuscript submissions: closed (28 February 2021) | Viewed by 14568

Special Issue Editor


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Guest Editor
College of Pharmacy and Institute of Bioequivalence and Bridging Study, Chonnam National University, 77 Yongbong-ro, Buk-Gu, Gwangju 61186, Republic of Korea
Interests: pharmacometrics; modeling; nanoformulation; drug delivery; lymph; herbal medicine; clinical study
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Special Issue Information

Dear Colleagues,

The lymphatic system plays an important role in the immune system’s recognition and response to disease. Furthermore, it is the main route for spreading cancer cells, viruses, and infections. The lymphatic system is an important target for developing new anticancer agents, imaging agents, vaccines, and immunotherapeutic agents. Therefore, studies on lymph targeting have been conducted to improve the therapeutic effect of anticancer and immunotherapeutic agents from the past. There have been several reports of formulation and evaluation techniques for nano- and microparticle-based drug delivery systems, but in vivo or pharmacokinetic (PK)/pharmacodynamics (PD) studies focused on the lymphatic system are still lacking. Research on the physiological system associated with lymphatics, drug formulations, and targeting to specific tissues may contribute to improving the lymphatic drug delivery. In particular, effective lymphatic delivery of anti-cancer and immunotherapeutic agents can lead to significant improvements in side effects and economics, and it will be very helpful in establishing therapeutic doses and regimens. This Special Issue will cover a wide range of current topics related to lymphatic delivery, including but not limited to drug formulation, nanomedicine, PK/PD studies, cancer therapy or immunotherapy, and related disciplines.

Prof. Dr. Yong-Bok Lee
Guest Editor

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Keywords

  • lymphatic system
  • drug delivery
  • drug formulation
  • nanomedicine
  • PK/PD model
  • anticancer agents
  • immunotherapeutic agents

Published Papers (4 papers)

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Research

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11 pages, 1717 KiB  
Article
Assessing Lymphatic Uptake of Lipids Using Magnetic Resonance Imaging: A Feasibility Study in Healthy Human Volunteers with Potential Application for Tracking Lymph Node Delivery of Drugs and Formulation Excipients
by Adelaide Jewell, Hannah Williams, Caroline L. Hoad, Paul R. Gellert, Marianne B. Ashford, James Butler, Snow Stolnik, David Scurr, Michael J. Stocks, Luca Marciani, Penny A. Gowland and Pavel Gershkovich
Pharmaceutics 2021, 13(9), 1343; https://doi.org/10.3390/pharmaceutics13091343 - 27 Aug 2021
Viewed by 2255
Abstract
Dietary lipids and some pharmaceutical lipid excipients can facilitate the targeted delivery of drugs to the intestinal lymphatics. Here, the feasibility of magnetic resonance imaging (MRI) for imaging lipid uptake into the intestinal lymphatics was assessed, shedding light on which lymph nodes can [...] Read more.
Dietary lipids and some pharmaceutical lipid excipients can facilitate the targeted delivery of drugs to the intestinal lymphatics. Here, the feasibility of magnetic resonance imaging (MRI) for imaging lipid uptake into the intestinal lymphatics was assessed, shedding light on which lymph nodes can be targeted using this approach. Three healthy male volunteers were scanned at 3.0 T at baseline, 120, 180, 240, and 300 min post high-fat meal. A sagittal multi-slice image was acquired using a diffusion-weighted whole-body imaging sequence with background suppression (DWIBS) (pre inversion TI = 260 ms). Changes in area, major, and minor axis length were compared at each time point. Apparent diffusion coefficient (ADC) was calculated (b = 0 and 600 s/mm2) across eight slices. An average of 22 nodes could be visualised across all time points. ADC increased at 120 and 180 min compared to the baseline in all three participants by an average of 9.2% and 6.8%, respectively. In two participants, mean node area and major axis lengths increased at 120 and 180 min relative to the baseline. In conclusion, the method described shows potential for repeated lymph node measurements and the tracking of lipid uptake into the lymphatics. Further studies should focus on methodology optimisation in a larger cohort. Full article
(This article belongs to the Special Issue Recent Approaches for Lymphatic Drug Delivery)
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12 pages, 3478 KiB  
Article
Lipid Nanoparticle-Mediated Lymphatic Delivery of Immunostimulatory Nucleic Acids
by Dongyoon Kim, Yina Wu, Gayong Shim and Yu-Kyoung Oh
Pharmaceutics 2021, 13(4), 490; https://doi.org/10.3390/pharmaceutics13040490 - 3 Apr 2021
Cited by 11 | Viewed by 3894
Abstract
Lymphatic delivery of a vaccine can be achieved using a dendritic cell (DC)-targeted delivery system that can cause DC to migrate to lymph nodes upon activation by an adjuvant. Here, we designed a mannose-modified cationic lipid nanoparticle (M-NP) to deliver the nucleic acid [...] Read more.
Lymphatic delivery of a vaccine can be achieved using a dendritic cell (DC)-targeted delivery system that can cause DC to migrate to lymph nodes upon activation by an adjuvant. Here, we designed a mannose-modified cationic lipid nanoparticle (M-NP) to deliver the nucleic acid adjuvant, polyinosinic:polycytidylic acid (PIC). PIC-loaded M-NP (PIC/M-NP) showed stable lipoplexes regardless of the ligand ratio and negligible cytotoxicity in bone marrow-derived DC. DC uptake of PIC/M-NP was demonstrated, and an increased mannose ligand ratio improved DC uptake efficiency. PIC/M-NP significantly promoted the maturation of bone marrow-derived DC, and local injection of PIC/M-NP to mice facilitated lymphatic delivery and activation (upon NP uptake) of DC. Our results support the potential of PIC/M-NP in delivering a nucleic acid adjuvant for the vaccination of antigens. Full article
(This article belongs to the Special Issue Recent Approaches for Lymphatic Drug Delivery)
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18 pages, 5317 KiB  
Article
Enhanced Lymphatic Delivery of Methotrexate Using W/O/W Nanoemulsion: In Vitro Characterization and Pharmacokinetic Study
by Ji-Hun Jang, Seung-Hyun Jeong and Yong-Bok Lee
Pharmaceutics 2020, 12(10), 978; https://doi.org/10.3390/pharmaceutics12100978 - 16 Oct 2020
Cited by 29 | Viewed by 3442
Abstract
Methotrexate, which is widely used in the treatment of cancer and immune-related diseases, has limitations in use because of its low bioavailability, short half-life, and tissue toxicity. Thus, in this study, a nano-sized water-in-oil-in-water (W/O/W) double emulsion containing methotrexate was prepared to enhance [...] Read more.
Methotrexate, which is widely used in the treatment of cancer and immune-related diseases, has limitations in use because of its low bioavailability, short half-life, and tissue toxicity. Thus, in this study, a nano-sized water-in-oil-in-water (W/O/W) double emulsion containing methotrexate was prepared to enhance its lymphatic delivery and bioavailability. Based on the results from solubility testing and a pseudo-ternary diagram study, olive oil as the oil, Labrasol as a surfactant, and ethanol as a co-surfactant, were selected as the optimal components for the nanoemulsion. The prepared nanoemulsion was evaluated for size, zeta potential, encapsulation efficiency, pH, morphology, and in vitro release profiles. Furthermore, pharmacokinetics and lymphatic targeting efficiency were assessed after oral and intravenous administration of methotrexate-loaded nanoemulsion to rats. Mean droplet size, zeta potential, encapsulation efficiency, and pH of formulated nanoemulsion were 173.77 ± 5.76 nm, −35.63 ± 0.78 mV, 90.37 ± 0.96%, and 4.07 ± 0.03, respectively. In vitro release profile of the formulation indicated a higher dissolution and faster rate of methotrexate than that of free drug. The prepared nanoemulsion showed significant increases in maximum plasma concentration, area under the plasma concentration-time curve, half-life, oral bioavailability, and lymphatic targeting efficiency in both oral and intravenous administration. Therefore, our research proposes a methotrexate-loaded nanoemulsion as a good candidate for enhancing targeted lymphatic delivery of methotrexate. Full article
(This article belongs to the Special Issue Recent Approaches for Lymphatic Drug Delivery)
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28 pages, 486 KiB  
Review
Focus on the Lymphatic Route to Optimize Drug Delivery in Cardiovascular Medicine
by Nolwenn Tessier, Fatma Moawad, Nada Amri, Davide Brambilla and Catherine Martel
Pharmaceutics 2021, 13(8), 1200; https://doi.org/10.3390/pharmaceutics13081200 - 4 Aug 2021
Cited by 5 | Viewed by 4103
Abstract
While oral agents have been the gold standard for cardiovascular disease therapy, the new generation of treatments is switching to other administration options that offer reduced dosing frequency and more efficacy. The lymphatic network is a unidirectional and low-pressure vascular system that is [...] Read more.
While oral agents have been the gold standard for cardiovascular disease therapy, the new generation of treatments is switching to other administration options that offer reduced dosing frequency and more efficacy. The lymphatic network is a unidirectional and low-pressure vascular system that is responsible for the absorption of interstitial fluids, molecules, and cells from the peripheral tissue, including the skin and the intestines. Targeting the lymphatic route for drug delivery employing traditional or new technologies and drug formulations is exponentially gaining attention in the quest to avoid the hepatic first-pass effect. The present review will give an overview of the current knowledge on the involvement of the lymphatic vessels in drug delivery in the context of cardiovascular disease. Full article
(This article belongs to the Special Issue Recent Approaches for Lymphatic Drug Delivery)
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