Blend of polymeric nanoparticles-in-microneedle arrays: A potential transepidermal route for genistein for anti-melanoma activity.

The current research work aimed to fabricate and investigate the impact of Genistein (GIN) alginate-chitosan nanoparticles (ACNPs) into dissolving microneedle arrays for the treatment for melanoma. The natural compound, GIN demonstrates high lipophilicity (log P value = 3.04), low aqueous solubility (<1 µg/mL), which further limits the entry into skin and hinders its clinical application in healthcare. Therefore, to overcome the challenges, GIN encapsulated ACNPs were incorporated into dissolvable microneedle arrays of Povidone K90/PVA biodegradable matrix, to obtain GINACNPs@MNs and achieve controlled release profile at the tumor site. The surface morphology of GINACNPs@MNs confirmed successful development of pyramidal-shaped sharp, projections. The ATR-FTIR, DSC, analysis displayed the drug-polymeric interactions, and proved that the bioactive remained in the amorphous state in the microneedle matrix. The dissolving microneedle arrays, GINACNPs@MNs exhibited controlled release (75 ± 1.24 %) for 144 h with elevated drug content (97.00 ± 0.42 %). The GINACNPs@MNs showed high mechanical strength and strong insertion capabilities in the human skin simulant, Parafilm® M. In addition, the TEWL analysis confirmed reversible disruption, restoration of skin barrier without affecting the skin integrity. Moreover, the cytotoxic assay on A375 cells revealed IC value of 25.08 μg/mL for GINACNPs@MNs compared to 30.55 μg/mL for GIN, and displayed superior in-vitro cytotoxic activity. Subsequently, the in-vivo subcutaneous A375-tumor bearing mouse model, confirmed high antitumor efficacy of GINACNPs@MNs and displayed tumor volume of 1055.10 mm in comparison to untreated group (2584.50 mm) after 18 days. Overall, the use of such novel, potential platform of GINACNPs@MNs offers minimally invasive approach for transepidermal delivery of GIN with high anti-melanoma activity.