Neratinib-loaded solid lipid nanoparticles in dissolvable microneedles for enhanced transdermal breast cancer therapy.

Abstract

Neratinib, an FDA-approved drug for breast cancer, faces challenges such as poor solubility, limited permeability, and adverse side effects. To address these issues, we developed dissolving microneedles incorporating Neratinib-loaded solid lipid nanoparticles (SLNs) to enhance transdermal delivery and minimize systemic toxicity. SLNs were formulated via hot homogenization using glyceryl monostearate as the lipid matrix and were evaluated for particle size, drug entrapment efficiency, drug loading, and stability. The optimized formulation (F7) exhibited a particle size of 209.4 nm and 87.57% entrapment efficiency. SLNs were integrated into microneedles using a micro-molding technique. Characterization included IR spectroscopy, scanning electron microscopy, mechanical strength, and insertion ability. Ex vivo studies on porcine skin demonstrated 80.71 ± 1.43% cumulative drug release over 24 h, confirming effective skin penetration. In vitro cytotoxicity on MCF-7 breast cancer cells showed greater efficacy of the SLN formulation over free Neratinib, with lower IC50 values (55.965 vs. 66.568 µg/mL), indicating enhanced cellular uptake and sustained release. The findings support dissolvable microneedles loaded with Neratinib-SLNs as a promising transdermal approach for targeted breast cancer therapy, offering improved bioavailability, reduced side effects, and better patient compliance.