CD44-targeted hyaluronic acid coated imiquimod lipid nanocapsules foster the efficacy against skin cancer: Attempt to conquer unfavorable side effects.

This study was executed to mitigate imiquimod (IMQ)-side effects and promote its anticancer potential against skin cancer via encapsulation in hyaluronic acid-coated lipid nanocapsules (HA-LNCs) for targeted topical delivery. The LNCs were prepared using the phase inversion technique. Optimized LNCs formulation was gained following 2 factorial design experiment to adjust the IMQ and CTAB concentrations. The two variables were found to significantly influence the dependent responses. The encapsulation efficiency of IMQ exceeded 97 %. HA coating provided a sustained release of IMQ from LNCs, with 63.81 ± 2.45 % of IMQ released after 24 h. Moreover, the ex-vivo human skin permeation study showed that 7.9-fold more IMQ was localized in all skin layers than that permeated. In vitro anticancer activity indicated that IMQ-HA-LNCs had higher cytotoxicity (IC = 22.39 μg/mL) compared to free IMQ (IC = 97.94 μg/mL). Further, in vivo studies revealed that encapsulation of IMQ in HA-LNCs enhanced its immunostimulatory potential and promoted its anti-tumor activity in competing skin cancer even in low doses compared to the untreated group and group treated with a brand product with no topical or systemic toxicity. The present study suggested that HA-LNCs with their mixed polymeric/lipophilic nature epitomize a promising strategy for safe topical delivery of poorly water-soluble candidates.