Farooq Mudassir, Usman Faisal, Naseem Mahrukh, Aati Hanan Y, Ahmad Hassan, Manee Sirikhwan, Khalil Ruqaiya, Khan Kashif Ur Rehman, Qureshi Muhammad Imran, Umair Muhammad
Department of Pharmaceutics, Faculty of Pharmacy, Bahauddin Zakariya University, Multan 60800, Pakistan.
Department of Zoology, University of Balochistan, Quetta 08770, Pakistan.
Pharmaceutics. 2023 Jan 24;15(2):389. doi: 10.3390/pharmaceutics15020389.
Hydroxypropyl β-cyclodextrin (HPβCD) based polymeric nanobeads containing voriconazole (VRC) were fabricated by free radical polymerization using '-methylene bisacrylamide (MBA) as a cross-linker, 2-acrylamide-2-methylpropane sulfonic acid (AMPS) as monomer and ammonium persulfate (APS) as reaction promoter. Optimized formulation (CDN5) had a particle size of 320 nm with a zeta potential of -35.5 mV and 87% EE. Scanning electron microscopy (SEM) depicted porous and non-spherical shaped beads. No evidence of chemical interaction was evident in FT-IR studies, whereas distinctive high-intensity VRC peaks were found superimposed in XRD. A stable polymeric network formation was evident in DSC studies owing to a lower breakdown in VRC loaded HPβCD in comparison to blank HPβCD. In vitro release studies showed 91 and 92% drug release for optimized formulation at pH 1.2 and 6.8, respectively, with first-order kinetics as the best-fit model and non-Fickian diffusion as the release mechanism. No evidence of toxicity was observed upon oral administration of HPβCD loaded VRC polymeric nanobeads owing to with cellular morphology of vital organs as observed in histopathology. Molecular docking indicates the amalgamation of the compounds highlighting the hydrophobic patching mediated by nanogel formulation. It can be concluded that the development of polymeric nanobeads can be a promising tool to enhance the solubility and efficacy of hydrophobic drugs such as VRC besides decreased toxicity and for effective management of fungal infections.
以羟丙基-β-环糊精（HPβCD）为基础、含有伏立康唑（VRC）的聚合物纳米珠，通过自由基聚合反应制备而成，使用N,N'-亚甲基双丙烯酰胺（MBA）作为交联剂，2-丙烯酰胺-2-甲基丙烷磺酸（AMPS）作为单体，过硫酸铵（APS）作为反应促进剂。优化后的配方（CDN5）粒径为320 nm，zeta电位为-35.5 mV，包封率为87%。扫描电子显微镜（SEM）显示珠子呈多孔且非球形。傅里叶变换红外光谱（FT-IR）研究中未发现化学相互作用的证据，而在X射线衍射（XRD）中发现有明显的高强度VRC峰叠加。差示扫描量热法（DSC）研究表明形成了稳定的聚合物网络，这是因为与空白HPβCD相比，负载VRC的HPβCD分解程度较低。体外释放研究表明，优化后的配方在pH 1.2和6.8时的药物释放率分别为91%和92%，最佳拟合模型为一级动力学，释放机制为非菲克扩散。口服负载VRC的HPβCD聚合物纳米珠后未观察到毒性迹象，组织病理学观察显示重要器官的细胞形态正常。分子对接表明化合物的融合突出了纳米凝胶制剂介导的疏水补丁作用。可以得出结论，聚合物纳米珠的开发可能是一种有前景的工具，除了能降低毒性外，还可提高伏立康唑等疏水药物的溶解度和疗效，从而有效治疗真菌感染。
