Ibrahim Al-Samadi Inas Essam, Omar Rashwan Kareem, Abdelmonem Rehab, I A Hamed Mohammed, Darwish Khaled M, Magdy William Mira, Abdellatif Menna M
Department of Industrial Pharmacy, College of Pharmaceutical Sciences and Drug Manufacturing, Misr University for Science and Technology, Giza, Egypt.
Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, October 6 University, Giza, Egypt.
Int J Pharm. 2025 May 30;677:125639. doi: 10.1016/j.ijpharm.2025.125639. Epub 2025 Apr 24.
The current research work explored the anti-inflammatory and antifungal activity of loratadine versus Candida albicans for treating vulvovaginal candidiasis (VVC). Loratadine was incorporated into terpene-enriched nanocarrier invasomes (IVS) using a thin-film hydration approach, where a D-optimal design was employed to investigate the lipid amount, terpene percent and type impact on the entrapment efficiency percentage (EE%), particle size (PS), polydispersity index (PDI), and zeta potential (ZP). The optimal formula was assessed regarding morphology, Fourier transform infrared (FTIR), in silico study, and differential scanning calorimetry (DSC). Subsequently, the optimal formula was incorporated into a gel base and characterized via ex vivo permeation studies. Lastly, in vivo investigations were performed to evaluate the performance of the loratadine-loaded IVS gel. The selected formula was spherical and had EE% of 91.95 ± 1.5 %, PS of 132.81 ± 2.7 nm, PDI of 0.326 ± 0.08, and ZP of -23.42 ± 0.38 mV. The FTIR and DSC studies verified the successful entrapment of the drug, while the in silico study demonstrated the thermodynamic stability of IVS. The IVS gel showed enhancement in drug deposition within vaginal tissues of 3.8 folds compared to free drug gel. Loratadine-loaded IVS gel showed remarkable improvement in eradicating candida infection by suppression of β-D-glucan. Furthermore, the IVS gel showed a significant anti-inflammatory effect reflected by marked suppression of NO, iNOS, COX-2, TNF-α, IL-1B and down-regulation in NF-κB, Src and Syk gene expressions. These results were confirmed via histopathological and immunohistological examinations. This work highlights the potential of loratadine as a promising therapy for VVC.
当前的研究工作探讨了氯雷他定对白色念珠菌的抗炎和抗真菌活性，以治疗外阴阴道念珠菌病（VVC）。采用薄膜水化法将氯雷他定载入富含萜类的纳米载体侵入体（IVS），并采用D-最优设计研究脂质用量、萜类百分比和类型对包封率（EE%）、粒径（PS）、多分散指数（PDI）和zeta电位（ZP）的影响。对最佳配方进行了形态学、傅里叶变换红外光谱（FTIR）、计算机模拟研究和差示扫描量热法（DSC）评估。随后，将最佳配方载入凝胶基质，并通过体外渗透研究进行表征。最后，进行体内研究以评估载氯雷他定IVS凝胶的性能。所选配方呈球形，EE%为91.95±1.5%，PS为132.81±2.7nm，PDI为0.326±0.08，ZP为-23.42±0.38mV。FTIR和DSC研究证实药物成功包封，而计算机模拟研究表明IVS具有热力学稳定性。与游离药物凝胶相比，IVS凝胶在阴道组织中的药物沉积增强了3.8倍。载氯雷他定IVS凝胶通过抑制β-D-葡聚糖在根除念珠菌感染方面表现出显著改善。此外，IVS凝胶显示出显著的抗炎作用，表现为对NO、iNOS、COX-2、TNF-α、IL-1B的显著抑制以及NF-κB、Src和Syk基因表达的下调。这些结果通过组织病理学和免疫组织化学检查得到证实。这项工作突出了氯雷他定作为VVC一种有前景治疗方法的潜力。
