Topical delivery of tlr agonists for the treatment of cutaneous melanoma

Neidich, Zachary, Joseph
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Karande, Pankaj
Zha, Helen
Shi, Sufei
Karande, Pankaj
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Chemical engineering
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Cutaneous melanoma is a cancer of the skin that affects approximately 100,000 people each year in the United States alone. The disease is typically treated with the surgical removal of the tumor and supplemented with chemotherapies which, due to their non-specificity, can result in unwanted toxicity to otherwise healthy cells elsewhere in the body. The proprietary molecule TLR-1 is a toll-like receptor (TLR) agonist that has been investigated as a treatment for melanoma for its anti-cancer properties. This molecule was successfully formulated into a topical hydrogel and delivered to cutaneous melanoma tumors via a transdermal pathway. Topical formulations containing TLR-1 in a hydrogel matrix limited tumor growth in a mouse model up to 5% of the volume of an untreated tumor after 27 days while maintaining low relative toxicity. Additionally, by examining the drying characteristics of these formulations, correlations were drawn between physical characteristics of formulations and tumor growth inhibition. Three proprietary TLR agonists were tested for their permeability and tissue retention properties. It was determined that TLR agonists with varying structures show varying permeability and tissue retention properties which can be leveraged for the most effective treatment of cutaneous melanoma.
School of Engineering
Dept. of Chemical and Biological Engineering
Rensselaer Polytechnic Institute, Troy, NY
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