The Exploitation of pH-Responsive Eudragit-Coated Mesoporous Silica Nanostructures in the Repurposing of Terbinafine Hydrochloride for Targeted Colon Cancer Inhibition: Design Optimization, In Vitro Characterization, and Cytotoxicity Assessment.

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.

Aceclofenac/Citronellol Oil Nanoemulsion Repurposing Study: Formulation, In Vitro Characterization, and In Silico Evaluation of Their Antiproliferative and Pro-Apoptotic Activity against Melanoma Cell Line.

Aceclofenac (ACF) is a widely used non-steroidal anti-inflammatory drug (NSAID) known for its effectiveness in treating pain and inflammation. Recent studies have demonstrated that ACF possesses antiproliferative properties, inhibiting the growth of cancer cells in various cancer cell lines. Citronellol, a monoterpenoid alcohol found in essential oils, exhibits antioxidant properties and activities such as inhibiting cell growth and acetylcholinesterase inhibition. In this study, the objective was to formulate and evaluate an aceclofenac/citronellol oil nanoemulsion for its antiproliferative effects on melanoma. The optimal concentrations of citronellol oil, Tween 80, and Transcutol HP were determined using a pseudoternary phase diagram. The formulated nanoemulsions were characterized for droplet size, zeta potential, thermophysical stability, and in vitro release. The selected formula (F1) consisted of citronellol oil (1 gm%), Tween 80 (4 gm%), and Transcutol HP (1 gm%). F1 exhibited a spherical appearance with high drug content, small droplet size, and acceptable negative zeta potential. The amorphous state of the drug in the nanoemulsion was confirmed by Differential Scanning Calorimetry, while FTIR analysis indicated its homogenous solubility. The nanoemulsion showed significant antiproliferative activity, with a lower IC50 value compared to aceclofenac or citronellol alone. Flow cytometric analysis revealed cell cycle arrest and increased apoptosis induced by the nanoemulsion. In silico studies provided insights into the molecular mechanism underlying the observed antitumor activity. In conclusion, the developed aceclofenac/citronellol oil nanoemulsion exhibited potent cytotoxicity and pro-apoptotic effects, suggesting its potential as a repurposed antiproliferative agent for melanoma treatment. In a future plan, further animal model research for validation is suggested.

Optimization of mirtazapine loaded into mesoporous silica nanostructures via Box-Behnken design: in-vitro characterization and in-vivo assessment.

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).