Propolis-Based Microneedles Incorporating Neratinib-Loaded Ocimum basilicum Essential Oil-Based Lipid Nanovesicles for Minimally Invasive Cancer Therapy: Formulation and In Vivo Evaluation in an Ehrlich Solid Tumor Model

Abstract

Background: Neratinib (NTB) is a potent pan-HER inhibitor, but its oral bioavailability is limited due to poor aqueous solubility, low permeability, and gastrointestinal toxicity. This study incorporated a bioactive transdermal system by incorporating NTB-loaded nanovesicles of Ocimum basilicum oil (NTB-OOs) into dissolving microneedles of PVA/PVP–propolis. Methods: Ocimum basilicum oil was characterized by gas chromatography–mass spectrometry (GC–MS). NTB-OOs were screened by I-optimal design and evaluated for vesicular properties, stability, release, skin permeation, and cytotoxicity. The optimized vesicles were loaded in propolis microneedles and evaluated mechanically, ex vivo, and in MCF-7 cells and Ehrlich solid carcinoma-bearing mice. Results: GC–MS revealed a volatile profile rich in linalool, methyl jasmonate, and a cyclopenta[g]-2-benzopyran derivative with reported antioxidant and anticancer activities. The optimized NTB-OOs showed a particle size of (198.9 ± 0.98 nm), entrapment efficiency of (88.9 ± 0.45%), PDI of (0.16 ± 0.01), zeta potential of (−23.1 ± 0.35 mV), and six-month stability. The microneedles provided zero-order release (48–50% after 24 h) and ex vivo permeation (~3500 µg/cm2), which were 2.7- and 1.2-fold higher than those of the NTB suspension and NTB-OOs, respectively. NTB-OOs reduced MCF-7 IC50 from 11.1 to 5.1 µg/mL. In vivo, NTB-OOs/propolis microneedles achieved 75.6% tumor inhibition, increased mean survival from 19 to 26.5 days, and raised the T/C ratio to 139.5%. They also induced apoptosis and downregulated the expression of HER-2, EGFR, VEGF-A, and Bcl-2. Conclusions: The multifunctional nanovesicle–propolis microneedle platform improves NTB solubilization, controlled release, dermal delivery, and antitumor efficacy, supporting its potential for minimally invasive localized breast cancer therapy.