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TRACK 1: Inspiring Innovation in Formulation, Bioprocessing, and Drug Delivery

Category: Poster Abstract

(T0930-01-02) Investigating the Effects of Multi-Drug-Loaded Nanospheres in Enhancing Antitumor Efficacy and Augmenting Immune Response Against Metastatic Melanoma

Tuesday, May 6, 2025
9:30 AM - 10:30 AM ET


Purpose: Melanoma, the deadliest form of skin cancer, primarily metastasizes through the lymphatic system, and the small molecules used for treatment do not reach therapeutic concentrations lymphatically.

Methods: Here, we develop drug-loaded nanoparticles designed for preferential lymphatic uptake to more effectively treat melanoma in the lymphatic system compared to orally administered small molecules in a clinically relevant transgenic mouse model.

Results: Multi-drug nanoparticles had high in vitro efficacy and synergy, a maximum tolerated dose in mice was established with once-weekly subcutaneous dosing, and nanoparticles demonstrated higher efficacy against lymphatic metastases in a transgenic mouse model compared to orally administered medications. Efficacy was especially pronounced in a sentinel lymph node. Nanoparticles were also able to increase systemic anti-tumor response.

Conclusion: This work indicates that developing nanoparticle-based drug delivery platforms for the treatment of lymphatically metastasizing melanoma may be a viable therapeutic option with the potential for clinical development.

Nanoparticles stability and characterization DT-NP: Debrafenib and Trametinib loaded nanoparticles. DTP-NP Debrafenib, Trametinib, and Pictilisib loaded nanoparticles

Effects of lymph node targeted two-drug and three-drug combination on metastasis of melanoma to Proximal lymph node and Spleen. DT-NP: Debrafenib and Trametinib loaded nanoparticles. DTP-NP Debrafenib, Trametinib, and Pictilisib loaded nanoparticles, P-NP: Pictilisib only nanoparticle, DT-S: Debrafenib, and Trametinib suspension.


Effects of lymph node targeted two-drug and three-drug combination on immune cell population in Spleen.
DT-NP: Debrafenib and Trametinib loaded nanoparticles. DTP-NP Debrafenib, Trametinib, and Pictilisib loaded nanoparticles, DT-S: Debrafenib, and Trametinib suspension.