Targeting Lymphatics for Nanoparticle Drug Delivery

McCright, Jacob; Naiknavare, Ritika; Yarmovsky, Jenny; Maisel, Katharina

doi:10.3389/fphar.2022.887402

Cited by 33 publications

(10 citation statements)

References 87 publications

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“…We formulated 40–150 nm PEGylated nanoparticles , from unmodified 103 ± 5 and 40 ± 2 nm. 100 and 40 nm nanoparticles were selected for this study as they lie within the 10–250 nm size range reported to enter lymphatic vessels and transport to lymph nodes. ,− Addition of PEG increased nanoparticle hydrodynamic diameter to 122 ± 6 nm (partial PEG) and 142 ± 3 nm (dense PEG) and 43 ± 2 nm (partial PEG) and 49 ± 3 nm (dense PEG) (Figure S1A). PEGylated nanoparticles also displayed a near-neutral ζ – potential (Figure S1B).…”

Section: Resultsmentioning

confidence: 99%

Para- and Transcellular Transport Kinetics of Nanoparticles across Lymphatic Endothelial Cells

McCright,

Yarmovsky,

Maisel

2023

Mol. Pharmaceutics

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Lymphatic vessels have received significant attention as drug delivery targets, as they shuttle materials from peripheral tissues to the lymph nodes, where adaptive immunity is formed. Delivery of immune modulatory materials to the lymph nodes via lymphatic vessels has been shown to enhance their efficacy and also improve the bioavailability of drugs when delivered to intestinal lymphatic vessels. In this study, we generated a three-compartment model of a lymphatic vessel with a set of kinematic differential equations to describe the transport of nanoparticles from the surrounding tissues into lymphatic vessels. We used previously published data and collected additional experimental parameters, including the transport efficiency of nanoparticles over time, and also examined how nanoparticle formulation affected the cellular transport mechanisms using small molecule inhibitors. These experimental data were incorporated into a system of kinematic differential equations, and nonlinear, least-squares curve fitting algorithms were employed to extrapolate transport coefficients within our model. The subsequent computational framework produced some of the first parameters to describe transport kinetics across lymphatic endothelial cells and allowed for the quantitative analysis of the driving mechanisms of transport into lymphatic vessels. Our model indicates that transcellular mechanisms, such as micro- and macropinocytosis, drive transport into lymphatics. This information is crucial to further design strategies that will modulate lymphatic transport for drug delivery, particularly in diseases like lymphedema, where normal lymphatic functions are impaired.

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Section: Resultsmentioning

confidence: 99%

Para- and Transcellular Transport Kinetics of Nanoparticles across Lymphatic Endothelial Cells

McCright,

Yarmovsky,

Maisel

2023

Mol. Pharmaceutics

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“…Particle size plays a pivotal role in optimizing lymphatic drug delivery [ 18 ]. Larger nanoparticles (>100 nm in diameter) and microparticles tend to be trapped in the interstitial matrix at the injection site or require phagocytosis by tissue dendritic cells or Langerhans cells for cell-mediated delivery to the lymph nodes.…”

Section: Discussionmentioning

confidence: 99%

Size-Dependent Effect of Indocyanine Green Nanoimaging Agent for Metastatic Lymph Node Detection

Le,

Kang,

Lee

et al. 2024

Biomater Res

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Identification of metastatic lymph nodes is a crucial step in lymph node dissection to prevent further cancer spread and recurrence. However, the current limitations in metastatic lymph node detection often result in extensive resection of normal lymph nodes, leading to serious complications. The clinical application of indocyanine green (ICG) as a tool for lymph node detection is challenging because of its short plasma half-life and rapid light-induced decomposition and clearance. To overcome this limitation, we used polydopamine nanoparticles (PNs) as carriers for ICG and screened for the optimal particle size for detecting metastatic lymph nodes. ICG/PNs with sizes of 80, 160, 300, and 600 nm were synthesized, and their ICG loading efficiency, physical stability, and lymph node distribution were evaluated. The ICG absorbed on the PNs was found to be protected from light degradation, and its retention at the lymph nodes was improved. Notably, the ICG/PNs favored the fluorescence signal at the metastatic lymph nodes compared to the nonmetastatic lymph nodes. Among the tested particle sizes, the 80-nm ICG/PN showed a higher distribution in the metastatic lymph nodes. This study suggests that the 80-nm ICG/PN is a potentially valuable reagent for the detection and diagnosis of lymph node metastasis.

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“…Overall, our work demonstrated that PEG density is an important consideration that modulates nanoparticle transport into lymphatic vessels. For further considerations in design criteria for lymphatic drug delivery, we point the readers to a recent review ( 77 ).…”

Section: Nanotechnology-enabled Lymphatic Vessel Targetingmentioning

confidence: 99%

Nanotechnologies for Physiology-Informed Drug Delivery to the Lymphatic System

Maisel

McClain

Bogseth

et al. 2023

Annu. Rev. Biomed. Eng.

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Accompanying the increasing translational impact of immunotherapeutic strategies to treat and prevent disease has been a broadening interest across both bioscience and bioengineering in the lymphatic system. Herein, the lymphatic system physiology, ranging from its tissue structures to immune functions and effects, is described. Design principles and engineering approaches to analyze and manipulate this tissue system in nanoparticle-based drug delivery applications are also elaborated. Expected final online publication date for the Annual Review of Biomedical Engineering, Volume 25 is June 2023. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

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Targeting Lymphatics for Nanoparticle Drug Delivery

Cited by 33 publications

References 87 publications

Para- and Transcellular Transport Kinetics of Nanoparticles across Lymphatic Endothelial Cells

Para- and Transcellular Transport Kinetics of Nanoparticles across Lymphatic Endothelial Cells

Size-Dependent Effect of Indocyanine Green Nanoimaging Agent for Metastatic Lymph Node Detection

Nanotechnologies for Physiology-Informed Drug Delivery to the Lymphatic System

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