Pharmaco-technical evaluation of statistically formulated and optimized dual drug-loaded silica nanoparticles for improved antifungal efficacy and wound healing

Masood, Amna and Maheen, Safirah and Khan, Hafeez Ullah and Shafqat, Syed Salman and Irshad, Misbah and Aslam, Iqra and Rasul, Akhtar and Bashir, Shahid and Zafar, Muhammad Nadeem Pharmaco-technical evaluation of statistically formulated and optimized dual drug-loaded silica nanoparticles for improved antifungal efficacy and wound healing. ACS Omega, 6 (12). pp. 8210-8225. ISSN 2470-1343, DOI https://doi.org/10.1021/acsomega.0c06242.

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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 EESA, EEKCZ, 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.

Item Type: Article
Funders: Higher Education Commission of Pakistan (NRPU Project) (6515/Punjab/NRPU/RD/HEC/2016)
Uncontrolled Keywords: Pharmaco-technical evaluation; Statistically formulated; Optimized dual drug-loaded silica nanoparticles; Improved antifungal efficacy; Wound healing
Subjects: Q Science > QD Chemistry
Divisions: Faculty of Science > Department of Physics
Depositing User: Ms Zaharah Ramly
Date Deposited: 08 Sep 2022 06:49
Last Modified: 08 Sep 2022 06:49
URI: http://eprints.um.edu.my/id/eprint/34228

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