Employment of mesoporous silica nanostructures (MSNs) in the drug delivery field has shown a significant potential for improving the oral delivery of active pharmaceutical products with low solubility in water. Mirtazapine (MRT) is a tetracyclic antidepressant with poor water solubility (BCS Class II), which was recently approved as a potent drug used to treat severe depression. The principle of this research is to optimize the incorporation of Mirtazapine into MSNs to improve its aqueous solubility, loading efficiency, release performance, and subsequent bioavailability. The formulation was optimized by using of Box-Behnken Design, which allows simultaneous estimation of the impact of different types of silica (SBA-15, MCM-41, and Aluminate-MCM-41), a different drug to silica ratios (33.33%, 49.99%, and 66.66%), and different drug loading procedures (Incipient wetness, solvent evaporation, and solvent impregnation) on the MRT loading efficiency, aqueous solubility and dissolution rate. The optimized formula was achieved by loading MRT into SBA-15 at 33.33% drug ratio prepared by the incipient wetness method, which displayed a loading efficiency of 104.05%, water solubility of 0.2 mg/ml, and 100% dissolution rate after 30 min. The pharmacokinetic profile of the optimized formula was obtained by conducting the in-vivo study in rabbits which showed a marked improvement (2.14-fold) in oral bioavailability greater than plain MRT. The physicochemical parameters and morphology of the optimized formula were characterized by; gas adsorption manometry, scanning electron microscopy (SEM), polarized light microscopy (PLM), Fourier-transform infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), and X-ray powder diffraction (XRPD).

The solid dispersion technique is the most effective and widely used approach for increasing the solubility and release of drugs that have low water solubility. Mirtazapine (MRT) is an atypical antidepressant used to treat severe depression. MRT has a low oral bioavailability (about 50%) due to its low water solubility (BCS class II). The study’s goal was to determine optimum conditions for incorporating MRT into various polymer types utilizing the solid dispersion (SD) technique, with the goal of selecting the most suitable formula with the optimal aqueous solubility, loading efficiency, and dissolution rate. The D-optimal design was used to pick the optimal response. The optimum formula was subjected to physicochemical evaluation by Fourier transform infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), X-ray powder diffraction (XRPD), and scanning electron microscopy (SEM). In vivo bioavailability study was conducted on white rabbits’ plasma samples. MRT-SDs were prepared by the solvent evaporation method using Eudragit (RL-100, RS-100, E-100, L-100–55), PVP K-30, and PEG 4000 with different drug/polymer percentages (33.33%, 49.99%, and 66.66%). Results showed that the optimum formula obtained using PVP K-30 at a drug percentage of 33.33% gave a loading efficiency of 100.93%, an aqueous solubility of 0.145 mg/ml, and a dissolution rate of 98.12% after 30 min. These findings demonstrated promising enhancement of MRT properties and increasing its oral bioavailability by 1.34-fold more than plain drug. Graphical Abstract

Targeted drug delivery is achieving great success in cancer therapy due to its potential to deliver drugs directly to the action site. Terbinafine hydrochloride (TER) is a broad-spectrum anti-fungal drug that has been found to have some potential anti-tumor effects in the treatment of colon cancer. We aimed here to design and develop pH-sensitive Eudragit (Eud)-coated mesoporous silica nanostructures (MSNs) to control drug release in response to changes in pH. The diffusion-supported loading (DiSupLo) technique was applied for loading TER into the MSNs. The formulation was optimized by a D-optimal design, which permits the concurrent assessment of the influence of drug/MSN%, coat concentration, and MSN type on the drug entrapment efficiency (EE) and its release performance. The optimal formula displayed a high EE of 96.49%, minimizing the release in pH 1.2 to 16.15% and maximizing the release in pH 7.4 to 78.09%. The cytotoxicity of the optimal formula on the colon cancer cells HT-29 was higher than it was with TER alone by 2.8-fold. Apoptosis in cancer cells exposed to the optimum formula was boosted as compared to what it was with the plain TER by 1.2-fold and it was more efficient in arresting cells during the G0/G1 and S stages of the cell cycle. Accordingly, the repurposing of TER utilizing Eud/MSNs is a promising technique for targeted colon cancer therapy.

Background: Skin cancer has become a global health issue because of increasing exposure to environmental contaminants and UV radiation. Terbinafine hydrochloride (TRB), a broad-spectrum antifungal medication, has demonstrated notable anti-tumor properties in previous studies; however, its repurposing for skin cancer therapy remains underexplored. Objective: This study reports for the first time, the development of a new delivery system: a nanoemulsion (NE)–foam hybrid system, i.e., “nanoemulfoam” (NEF), designed to enhance the topical TRB delivery to the skin. The study applied this new hybrid system on TRB for managing skin cancer. Method: The TRB-loaded NEF was produced by loading TRB into a liquid NE. then this was incorporated into a liquid foam base and actuated into foam using a non-propellant mechanism. The NE was developed utilizing peppermint oil as the oil phase and Tween-20/ethanol as the surfactant/co-surfactant combination (Smix). The formulation underwent optimization using the D-optimal design that enabled the simultaneous evaluation of the impact of oil concentration and Tween 20 concentration in the Smix on the particle size (PS), zeta potential (ZP), and dissolution efficiency percent (DE%). Results: The optimal NE formula displayed a small PS of 186.60 ± 2.84 nm, ZP of −13.90 ± 0.99 mV, and DE% of 68.50 ± 1.78% (mean ± SD, n = 3). After incorporation into the foam system, the produced TRB-loaded NEF demonstrated a 7.43-fold increase in the drug transdermal flux in comparison with plain drug foam (p < 0.05). The TRB-loaded NEF showed no signs of inflammation or irritation when applied to abdominal rabbit skin, indicating its safety. The optimum formula exhibited a statistically significant 10-fold increase in cytotoxicity against A-431 skin cancer cells compared to TRB alone, along with a 1.54-fold increase in apoptosis (p < 0.05). Molecular docking studies targeting CDK2, a key regulator of cell proliferation and a known TRB target, revealed that TRB displayed highly favorable binding scores compared to the reference drug. Conclusions: The TRB-loaded NEF represents a promising nanotechnology-based approach for the topical treatment of skin cancer, supporting further investigation toward clinical translation.