Microneedles integrated with atorvastatin-loaded pumpkisomes for breast cancer therapy: A localized delivery approach

Breast cancer is the most common invasive cancer in women worldwide, having a significant impact on women's well-being. Early diagnosis of breast cancer followed by appropriate treatment is considered the best survival factor. Microneedles (MN) have been utilized for non-invasive localized breast cancer treatment. The combination of nano-carriers with MN technology represents an appealing strategy for improving drug delivery efficacy. It is worth noting that atorvastatin (ATV) has received substantial interest as a drug with potential anticancer activity. Our study aimed to formulate an ATV-loaded bioactive pumpkin seed oil vesicular nanocarrier; pumpkisomes (PUMP) for enhanced localized delivery to breast cancer using MN. The selected PUMP formulation had a particle size of 151.8 ± 2.7 nm, zeta potential of -54.1 mV, and % entrapment efficiency of 73 %. PUMP showed a sustained ATV release, potent selective cytotoxic effect (IC₅₀ of 2.82 ± 0.02 μg/mL), enhanced internalization (2.8-fold increase compared to the free drug), and potent anti-migratory effect on MDA-MB-231 cells (21.15 ± 3.6 % wound closure compared to 80.81 ± 4.1 % for free drug). Moreover, integrating ATV-PUMP in dissolving microneedles (ATV-PUMP@dMN) showed a quick dissolution rate and appropriate mechanical strength with high piercing efficiency. ATV permeation across the skin from ATV-PUMP@dMN was also improved (1.8-fold increase compared to ATV-PUMP@gel). ATV-PUMP@dMN demonstrated an efficient anticancer effect when applied in an Ehrlich ascites mammary tumor model attaining significant improvement in ATV antiproliferative (PTEN and Ki-67), antiangiogenic (VEGF) and apoptotic (Bcl2, Bax and caspase3) effects restoring tumor biomarkers to levels comparable to the negative control group. Thus, our study presents PUMP as a novel and promising bioactive vesicular nanosystem with potential synergistic effect with ATV or other antitumor drugs. PUMP-integrated MN could be considered a promising platform for future applications in localized breast cancer therapy.