Pharmaco-Technical Evaluation of Statistically Formulated and Optimized Dual Drug-Loaded Silica Nanoparticles for Improved Antifungal Efficacy and Wound Healing

Abstract

The current research aimed at designing mesoporous silica nanoparticles (MSNs) for a controlled coadministration of salicylic acid (SA) and ketoconazole (KCZ) to effectively treat highly resistant fungal infections. The sol−gel method was used to formulate MSNs, which were further optimized using central composite rotatable design (CCRD) by investigating mathematical impact of independent formulation variables such as pH, stirring time, and stirring speed on dependent variables entrapment efficiency (EE) and drug release. The selected optimized MSNs and pure drugs were subjected to comparative in vitro/in vivo antifungal studies, skin irritation, cytotoxicity, and histopathological evaluations. The obtained negatively charged (−23.1), free flowing spherical, highly porous structured MSNs having a size distribution of 300−500 nm were suggestive of high storage stability and improved cell proliferation due to enhanced oxygen supply to cells. The physico-chemical evaluation of SA/KCZ-loaded MSNs performed through powder X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), and thermal gravimetric analysis (TGA) indicates absolute lack of any interaction between formulation components and successful encapsulation of both drugs in MSNs. The EE SA , EE KCZ , SA release, and KCZ release varied significantly from 34 to 89%, 36 to 85%, 39 to 88%, and 43 to 90%, respectively, indicating the quadratic impact of formulation variables on obtained MSNs. For MSNs, the skin tolerability and cell viability percentage rate were also having an extraordinary advantage over suspension of pure drugs. The optimized SA/KCZ-loaded MSNs demonstrated comparatively enhanced in vitro/in vivo antifungal activities and rapid wound healing efficacy in histopathological evaluation without any skin irritation impact, suggesting the MSNs potential for the simultaneous codelivery of antifungal and keratolyic agents in sustained release fashion.

Mesoporous Silica Particles as Drug Delivery Systems—The State of the Art in Loading Methods and the Recent Progress in Analytical Techniques for Monitoring These Processes

“…High performance liquid chromatography (HPLC) is used to separate, identify, and quantify different mixture components, and it is applied to confirm the chemical stability of the molecules loaded into nanoparticles [237,238], entrapment efficiency [239,240], and to obtain the drug release curves, as demonstrated in the release studies of naproxen [15], paclitaxel [87], resveratrol [241], felodipine and furosemide [17], and many others. For the determination of drug loading efficiency, after the completion of the loading process, samples undergo centrifugation and the unloaded molecules present in the supernatant are analyzed by HPLC, as was shown in the case of rifampin [242].…”

Systematic Development of Solid Lipid Nanoparticles of Abiraterone Acetate with Improved Oral Bioavailability and Anticancer Activity for Prostate Carcinoma Treatment

“…The rational selection of excipients and their concentrations was helpful in selecting the SLNs with smaller particle size and good polydispersity index. , Figure B revealed the zeta potential value of 110 mV for the optimized SLNs measured using photon correlation spectroscopy, which indicated the stable nature of the optimized SLN formulation. It is quite usual that nanoparticles with zeta potential between −30 and 30 mV demonstrate good colloidal stability for longer periods of time. − However, the SLNs of abiraterone acetate prepared in the current work showed very high zeta potential which could be attributed to the presence of lipids and emulgents selected for the preparation of the SLNs.…”

“…It is quite usual that nanoparticles with zeta potential between −30 and 30 mV demonstrate good colloidal stability for longer periods of time. 28−30 However, 30 the SLNs of abiraterone 29 acetate prepared in the current work showed very high zeta potential which could be attributed to the presence of lipids and emulgents selected for the preparation of the SLNs.…”

Multifunctional mesoporous silica-cerium oxide nanozymes facilitate miR129 delivery for high-quality healing of radiation-induced skin injury

“…In the treatment of skin infections, nanosilica drug loading is a novel method for drug administration. Mesoporous silica (MS) is a promising drug carrier due to its specific surface area, large pore volume, high loading capacity and biocompatibility [ 12 ]. Traditional drug delivery systems produce several local adverse effects, such as burning sensation, skin irritation, greasy, stinging, pruritic rash, erythema and tenderness, thus making them unacceptable [ 4 ].…”