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Purpose <p>There are no preventive and few therapeutic options for melanoma, an aggressive skin cancer, especially in situations where N-Ras mutations are present. The new pan-Ras inhibitor ADT-007 has promise for treating melanoma. This study aimed to prepare a topical molecular targeted drug for prevention or treatment of early-stage melanoma using ultraflexible liposomes (UFLs) dispersed in a carbomer gel.</p> Methods <p>ADT-containing UFLs were evaluated for anticancer efficacy and selectivity in vitro using melanoma cell lines and normal keratinocytes. Comparisons were made between UFLs and traditional liposomes (TL) in terms of drug release, encapsulation efficiency, and skin permeation. Permeation tests were conducted using the skin-like Strat-M membrane. Stability of UFLs was assessed at 4°C.</p> Results <p>UFLs exhibited enhanced ADT-007 drug release and higher encapsulation efficiency compared to TL. ADT-007 from UFL carbomer gels penetrated more readily through the Strat-M membrane than that from TL or ADT-007 alone. UFLs were incredibly stable in regard to size and encapsulation efficiency, particularly at 4°C. This combination demonstrated low cytotoxicity against human keratinocytes but high toxicity against various human melanoma cancer cells, especially those harboring N-Ras mutations.</p> Conclusions <p>This study highlights the use of UFL-based gels as a promising strategy for prevention or targeted melanoma therapy by providing enhanced drug delivery, stability, and cancer cell selectivity.</p>

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Preparation and Characterization of Novel Pan-RAS Inhibitor Loaded Ultraflexible Liposomes for the Topical Prevention or Treatment of Skin Melanoma

  • 期刊论文

  • 发表日期：

    2025年11月26日

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  • Shivani A. Dave,
  • Adam B. Keeton,
  • Gary A. Piazza,
  • Anthony J. Di Pasqua

摘要

Purpose

There are no preventive and few therapeutic options for melanoma, an aggressive skin cancer, especially in situations where N-Ras mutations are present. The new pan-Ras inhibitor ADT-007 has promise for treating melanoma. This study aimed to prepare a topical molecular targeted drug for prevention or treatment of early-stage melanoma using ultraflexible liposomes (UFLs) dispersed in a carbomer gel.

Methods

ADT-containing UFLs were evaluated for anticancer efficacy and selectivity in vitro using melanoma cell lines and normal keratinocytes. Comparisons were made between UFLs and traditional liposomes (TL) in terms of drug release, encapsulation efficiency, and skin permeation. Permeation tests were conducted using the skin-like Strat-M membrane. Stability of UFLs was assessed at 4°C.

Results

UFLs exhibited enhanced ADT-007 drug release and higher encapsulation efficiency compared to TL. ADT-007 from UFL carbomer gels penetrated more readily through the Strat-M membrane than that from TL or ADT-007 alone. UFLs were incredibly stable in regard to size and encapsulation efficiency, particularly at 4°C. This combination demonstrated low cytotoxicity against human keratinocytes but high toxicity against various human melanoma cancer cells, especially those harboring N-Ras mutations.

Conclusions

This study highlights the use of UFL-based gels as a promising strategy for prevention or targeted melanoma therapy by providing enhanced drug delivery, stability, and cancer cell selectivity.