Department of Pharmaceutics, College of Pharmacy, University of Sargodha, Sargodha 40100, Pakistan.
Department of Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences, Government College University Faisalabad, Faisalabad 38000, Pakistan.
Molecules. 2023 Jul 5;28(13):5233. doi: 10.3390/molecules28135233.
The current study focused on the fabrication of a well-designed, biocompatible, physically stable, non-irritating and highly porous gelatin scaffold loaded with controlled-release triamcinolone acetonide (TA) and econazole nitrate (EN) co-loaded into mesoporous silica nanoparticles (EN-TA-loaded MSNs) to provide a better long-lasting antifungal therapeutic effect with minimal unfavorable effects. Optimization of the MSNs-loaded scaffold was performed using central composite rotatable design (CCRD), where the effect of gelatin concentration (X1), plasticizer (X2) and freezing time (X3) on the entrapment of EN (Y1) and TA (Y2) and on the release of EN (Y3) and TA (Y4) from the scaffold were studied. The significant compatibility of all formulation ingredients with both drugs was established from XRD, DSC and FT-IR spectra analyses while SEM and zeta studies represented a very precise unvarying distribution of the loaded MSNs in the porous structure of the scaffold. The stability of the optimized scaffold was confirmed from zeta potential analysis (-16.20 mV), and it exhibited higher entrapment efficiency (94%) and the slower (34%) release of both drugs. During in vitro and in vivo antifungal studies against , the MSNs-loaded scaffold was comparatively superior in the eradication of fungal infections as a greater zone of inhibition was observed for the optimized scaffold (16.91 mm) as compared to the pure drugs suspension (14.10 mm). Similarly, the MSNs-loaded scaffold showed a decreased cytotoxicity because the cell survival rate in the scaffold presence was 89% while the cell survival rate was 85% in the case of the pure drugs, and the MSNs-loaded scaffold did not indicate any grade of erythema on the skin in comparison to the pure medicinal agents. Conclusively, the scaffold-loaded nanoparticles containing the combined therapy appear to possess a strong prospective for enhancing patients' adherence and therapy tolerance by yielding improved synergistic antifungal efficacy at a low dose with abridged toxicity and augmented wound-healing impact.
当前的研究侧重于设计一种生物相容性好、物理稳定性高、无刺激性且具有高度多孔性的明胶支架，该支架负载有控释曲安奈德（TA）和硝酸益康唑（EN）共负载到介孔硅纳米粒子（EN-TA 负载的 MSNs）中，以提供更好的长效抗真菌治疗效果，同时最小化不良影响。通过中心复合旋转设计（CCRD）对负载 MSNs 的支架进行了优化，研究了明胶浓度（X1）、增塑剂（X2）和冷冻时间（X3）对 EN（Y1）和 TA（Y2）的包封以及支架中 EN（Y3）和 TA（Y4）的释放的影响。从 XRD、DSC 和 FT-IR 光谱分析中确定了所有配方成分与两种药物的高度兼容性，而 SEM 和 zeta 研究则代表了负载的 MSNs 在支架多孔结构中非常精确的均匀分布。从zeta 电位分析（-16.20 mV）确认了优化支架的稳定性，并且它表现出更高的包封效率（94%）和更慢（34%）的两种药物释放。在体外和体内抗真菌研究中，负载 MSNs 的支架在消除真菌感染方面具有优越性，因为观察到优化支架的抑菌圈（16.91 mm）比纯药物悬浮液（14.10 mm）更大。同样，负载 MSNs 的支架表现出较低的细胞毒性，因为支架存在时细胞存活率为 89%，而纯药物时细胞存活率为 85%，并且与纯药物相比，负载 MSNs 的支架在皮肤上没有显示任何程度的红斑。总之，载药纳米粒子的支架似乎具有增强患者依从性和治疗耐受性的强大潜力，通过以低剂量产生协同抗真菌疗效，同时减少毒性和增强伤口愈合作用。
