Zhang, Ziqian; Huang, Yixian; West III, Raymond E; Mahesh, Deepika; Oberly, Patrick J; Li, Shichen; Luo, Zhangyi; Chen, Yuang; Huang, Haozhe; Bain, Daniel J

DOI:

Abstract

The persistence of HIV reservoirs within the lymphatic system represents a significant challenge to achieving a complete cure for people with HIV, largely due to inadequate concentrations of antiretroviral drugs (ARVs) in lymphatic tissues under current treatment regimens. Thus, developing innovative therapeutic strategies to enhance ARV concentrations in the lymphatic system may provide a paradigm shift toward an HIV cure. Here, we describe a novel delivery strategy involving an Evans Blue (EB) prodrug conjugate with a model ARV (dolutegravir, DTG), designed to bind albumin with high affinity and reach lymph nodes (LNs) via albumin-mediated trans-endothelial transport through transcytosis. EB modification substantially improved the distribution of conjugated molecules to LNs throughout the body, and the hEB-DTG prodrug significantly elevated DTG concentrations in both blood and LNs over time, suggesting a promising strategy for eradicating HIV reservoir.

Keywords

Drug delivery ; Evans Blue ; albumin ; lymph node ; nanomedicine

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