Skin cancer remains a major global health issue, with non-melanoma variants such as squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) showing a rising incidence worldwide. Despite the substantial advancements in the medical field, traditional treatment options such as surgery, chemotherapy, radiation therapy, and topical drugs still suffer from several shortcomings, which include poor drug absorption, systemic toxicity, recurrence, and lack of specificity in targeting these tumors. The present study was undertaken to develop and evaluate hyaluronic acid-imiquimod (HA-IMQ) conjugate incorporated into a niosomal gel system aimed at achieving targeted and sustained topical delivery for skin cancer therapy. The HA-IMQ conjugate was synthesized and verified through FTIR spectroscopy and 1H NMR spectroscopy. Optimization of niosomal formulation was carried out using Box-Behnken design, yielding vesicles with average diameter of 566.9 ± 5.42 nm, polydispersity index of 0.323 ± 0.02 and an entrapment efficiency of 71.84 ± 3.99%. The in vitro release was found to be 81.45 ± 1.11% over a period of 72 h indicating controlled and prolonged delivery behavior. Cytotoxicity assays against A431 carcinoma cells revealed superior anticancer efficacy of HA-IMQ-NIO and HA-IMQ-NIO-G compared to free IMQ. Increased cellular uptake is supported by increased generation of reactive oxygen species (ROS), mitochondrial membrane depolarization, and nuclear events. It suggests that receptor-mediated uptake takes place via mitochondrial-dependent apoptosis. This enhanced efficacy result of CD44 receptor mediated targeting facilitated by hyaluronic acid. The HA-IMQ niosomal gel formulation represents a potentially effective noninvasive approach for targeting and sustained delivery to treat skin cancer.
Tomar et al. (Tue,) studied this question.