Mohsen Amira Mohamed
Pharmaceutical Technology Department, National Research Centre, El-Buhouth St., Dokki, Cairo 12622, Egypt.
J Pharm Sci. 2022 Feb;111(2):458-468. doi: 10.1016/j.xphs.2021.09.019. Epub 2021 Sep 20.
Terconazole (TCZ) is a broad-spectrum antifungal triazole that is particularly active against Candida species, but its poor water solubility hinders its ocular absorption and restricts its application. This study aims to fabricate TCZ-loaded cationic polymeric nanoparticles to enhance the ocular delivery and antimycotic activity of terconazole. TCZ-loaded nanoparticles were developed by nanoprecipitation method employing Eudragit RLPO®. They were characterized by entrapment efficiency (EE%), particle size (PS), zeta potential (ZP), morphology, Fourier transform infrared spectroscopy (FT-IR), and X-ray powder diffraction (XRPD). In-vitro antimycotic activity was evaluated by measuring zone of inhibition (ZI), minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC). The developed nanoparticles were spherical with moderate to high EE% (44.03-71.14%), a nanometric PS (49.41-78.72 nm), and a positively charged ZP (≥ +21.47). In-vitro release studies revealed sustained release of drug up to 24 h. FT-IR of TCZ-loaded nanoparticles revealed distinctive peaks for Eudragit RLPO® and Poloxamer-188, with disappearance of the TCZ characteristic peaks. XRPD revealed the amorphous state of TCZ within the polymer matrix. Mucoadhesive studies proved the mucoadhesive property of the developed TCZ nanoparticles. In-vitro antimycotic studies, assessed by ZI, MIC and MFC, revealed enhanced antimycotic activity of TCZ-loaded nanoparticles against Candida albicans, relative to plain TCZ. No irritation or abnormal changes to the rabbits' eyes for plain and medicated polymeric nanoparticles were found by the in-vivo Draize test. These findings reveal that the cationic polymeric nanoparticles can be regarded as a potential drug delivery system for enhancing the ocular antimycotic activity of TCZ.
特康唑（TCZ）是一种广谱抗真菌三唑类药物，对念珠菌属具有特别强的活性，但其水溶性差阻碍了其眼部吸收并限制了其应用。本研究旨在制备载有特康唑的阳离子聚合物纳米粒，以增强特康唑的眼部递送和抗真菌活性。采用Eudragit RLPO®通过纳米沉淀法制备了载有特康唑的纳米粒。通过包封率（EE%）、粒径（PS）、zeta电位（ZP）、形态、傅里叶变换红外光谱（FT-IR）和X射线粉末衍射（XRPD）对其进行了表征。通过测量抑菌圈（ZI）、最低抑菌浓度（MIC）和最低杀菌浓度（MFC）评估体外抗真菌活性。所制备的纳米粒呈球形，包封率适中至高（44.03 - 71.14%），纳米级粒径（49.41 - 78.72 nm），且带正电荷的zeta电位（≥ +21.47）。体外释放研究表明药物可持续释放长达24小时。载有特康唑的纳米粒的FT-IR显示出Eudragit RLPO®和泊洛沙姆188的特征峰，而特康唑的特征峰消失。XRPD显示聚合物基质中特康唑为无定形状态。黏膜黏附研究证明了所制备的载有特康唑的纳米粒的黏膜黏附特性。通过ZI、MIC和MFC评估的体外抗真菌研究表明，相对于普通特康唑，载有特康唑的纳米粒对白色念珠菌的抗真菌活性增强。体内Draize试验未发现普通和含药聚合物纳米粒对兔眼有刺激或异常变化。这些发现表明，阳离子聚合物纳米粒可被视为一种潜在的药物递送系统，用于增强特康唑的眼部抗真菌活性。
