Kucuk Israfil, Ahmad Zeeshan, Edirisinghe Mohan, Orlu-Gul Mine
University College London, Department of Mechanical Engineering, Torrington Place, London WC1E 7JE, UK; Firat University, Faculty of Engineering, Department of Metallurgical and Materials Engineering, Elazig 23279, Turkey.
De Montfort University, Leicester School of Pharmacy, Leicester LE1 9BH, UK.
Int J Pharm. 2014 Sep 10;472(1-2):339-46. doi: 10.1016/j.ijpharm.2014.06.023. Epub 2014 Jun 16.
Itraconazole is widely used as an anti-fungal drug to treat infections. However, its poor aqueous solubility results in low bioavailability. The aim of the present study was to improve the drug release profile by preparing surface itraconazole adsorbed polymethylsilsesquioxane (PMSQ) nanospheres using a V-junction microfluidic (VJM) device. In order to generate nanospheres with rough surface, the process flow rate of perfluorohexane (PFH) was set between 50 and 300 μl min(-1) while the flow rate of PMSQ and itraconazole solution were constant at 300 μl min(-1). Variations in the PFH flow rate enable the controlled size generation of nanospheres. PMSQ nanospheres adsorbing itraconazole were characterized by SEM, FTIR and Zetasizer. The release of itraconazole from PMSQ nanosphere surface was measured using UV spectroscopy. Nanosphere formulations with a range of sphere size (120, 320 and 800 nm diameter) were generated and drug release was studied. 120 nm itraconazole coated PMSQ nanospheres were found to present highest drug encapsulation efficiency and 13% drug loading in a more reproducible manner compared to 320 nm and 800 nm sized nanosphere formulations. Moreover, 120 nm itraconazole coated PMSQ nanospheres (encapsulation efficiency: 88%) showed higher encapsulation efficiency compared to 320 nm (encapsulation efficiency: 74%) and 800 nm (encapsulation efficiency: 62%) sized nanosphere formulations. The itraconazole coated PMSQ nanospheres were prepared continuously at the rate of 2.6 × 10(6) per minute via VJM device. Overall the VJM device enabled the preparation of monodisperse surface itraconazole adsorbed nanospheres with controlled in vitro drug release profile.
伊曲康唑作为一种抗真菌药物被广泛用于治疗感染。然而，其较差的水溶性导致生物利用度较低。本研究的目的是通过使用V型微流体（VJM）装置制备表面吸附伊曲康唑的聚甲基倍半硅氧烷（PMSQ）纳米球来改善药物释放曲线。为了生成具有粗糙表面的纳米球，全氟己烷（PFH）的工艺流速设定在50至300 μl min⁻¹之间，而PMSQ和伊曲康唑溶液的流速恒定在300 μl min⁻¹。PFH流速的变化能够控制纳米球的尺寸生成。通过扫描电子显微镜（SEM）、傅里叶变换红外光谱（FTIR）和Zeta电位分析仪对吸附伊曲康唑的PMSQ纳米球进行了表征。使用紫外光谱法测量伊曲康唑从PMSQ纳米球表面的释放。制备了一系列不同尺寸（直径分别为120、320和800 nm）的纳米球制剂并研究了药物释放情况。与320 nm和800 nm尺寸的纳米球制剂相比，发现120 nm伊曲康唑包衣的PMSQ纳米球以更可重复的方式呈现出最高的药物包封率和13%的载药量。此外，120 nm伊曲康唑包衣的PMSQ纳米球（包封率：88%）与320 nm（包封率：74%）和800 nm（包封率：62%）尺寸的纳米球制剂相比，显示出更高的包封率。通过VJM装置以每分钟2.6×10⁶的速率连续制备伊曲康唑包衣的PMSQ纳米球。总体而言，VJM装置能够制备具有可控体外药物释放曲线的单分散表面吸附伊曲康唑的纳米球。
