High-Density Lipoprotein Composition Influences Lymphatic Transport after Subcutaneous Administration

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Immunology

Background:

• Subcutaneous administration of nanoparticles can enhance immunotherapy and vaccine delivery to lymph nodes.
• Endogenous high-density lipoproteins (HDLs) naturally travel through lymphatic vessels, suggesting their potential as drug carriers.
• Understanding HDL transport mechanisms in lymphatics is crucial for developing targeted therapies.

Purpose of the Study:

• To investigate how HDL physicochemical properties influence their lymphatic transport and lymph node retention after subcutaneous administration.
• To determine the optimal design of HDL-based nanoparticles for effective lymphatic targeting.

Main Methods:

• Prepared and characterized various endogenous and synthetic HDLs with similar sizes (10-20 nm) and surface charge.
• Radiolabeled HDLs and administered them subcutaneously into rats with lymphatic cannulation.
• Quantified radiolabel recovery in lymph, plasma, lymph nodes, and tissues to assess transport and retention.

Main Results:

• All HDLs preferentially entered lymphatic vessels over blood vessels, with high lymph-to-plasma concentration ratios (up to 100:1).
• Lymph node retention of HDLs positively correlated with increasing negative surface charge, linked to surface composition.
• HDL lymphatic transport was influenced more by unique composition than by similar physical properties.

Conclusions:

• HDL composition, particularly surface charge, significantly impacts lymphatic transport and lymph node retention.
• Findings provide insights for designing HDL-based nanoparticles for targeted delivery of immunotherapies and vaccines to lymph nodes.
• This research supports the development of more effective and less toxic drug delivery systems via lymphatic targeting.