Hyaluronic Acid Conjugates of Vorinostat and Bexarotene for Treatment of Cutaneous Malignancies

• DOI: 10.1002/adtp.202000116
• Publication Date: 2020-08-03T06:05:55Z
• Authors: Marwa A. Sallam; Supriya Prakash; Vinu Krishnan; Kristina Todorova; Anna Mandinova; Samir Mitragotri
• Keywords: Bexarotene; Vorinostat; Human skin; Ex vivo

Abstract Skin cancer is the most common class of malignancies in humans with increasing incidence worldwide. Although surgery remains treatment approach, relapses after necessitate other options. There an clinical demand for topical treatments skin that can improve drug's cutaneous localization while limiting systemic absorption. In this study, hyaluronic acid (HA) conjugates are successfully synthesized by attaching a third‐generation retinoid (bexarotene) and histone deacetylase inhibitor (vorinostat) to HA via ester bonds. The characterized ensure identity quantify total drug loading. HA‐BEX HA‐VOR exhibit synergistic anticancer effect against human squamous cell carcinoma (A431) T lymphoma lines (HUT 78) at specific ratios minimal adverse on primary keratinocytes fibroblasts. Confocal microscopy demonstrates inside cells. Ex vivo permeation studies explants confirm their ability penetrate stratum corneum reach deep dermis. Biodistribution reveal presence both drugs epidermis dermis amounts sufficient exert inhibitory HA‐bexarotene‐vorinostat offer excellent therapeutic option treat cancers.