Hashemi Dehaghi Mohadeseh, Haeri Azadeh, Keshvari Hamid, Abbasian Zahra, Dadashzadeh Simin
Department of Pharmaceutics, School of Pharmacy, Shahid Beheshti University of Medical Science, Tehran, Iran.
Department of Biomedical Engineering, Faculty of New Science and Technology, Tehran University, Tehran, Iran.
Iran J Pharm Res. 2017 Spring;16(2):413-422.
Glaucoma is a common progressive eye disorder and the treatment strategies will benefit from nanoparticulate delivery systems with high drug loading and sustained delivery of intraocular pressure lowering agents. Niosomes have been reported as a novel approach to improve drug low corneal penetration and bioavailability characteristics. Along with this, poor entrapment efficiency of hydrophilic drug in niosomal formulation remains as a major formulation challenge. Taking this perspective into consideration, dorzolamide niosomes were prepared employing two different loading methodologies (passive and remote loading methods) and the effects of various formulation variables (lipid to drug ratio, cholesterol percentage, drug concentration, freeze/thaw cycles, TPGS content, and external and internal buffer molarity and pH) on encapsulation efficiency were assessed. Encapsulation of dorzolamide within niosomes increased remarkably by the incorporation of higher cholesterol percentage as well as increasing the total lipid concentration. Remote loading method showed higher efficacy for drug entrapment compared to passive loading technique. Incorporation of TPGS in bilayer led to decrease in EE; however, retarded drug release rate. Scanning electron microscopy (SEM) studies confirmed homogeneous particle distribution, and spherical shape with smooth surface. In conclusion, the highest encapsulation can be obtained using phosphate gradient method and 50% cholesterol in Span 60 niosomal formulation.
青光眼是一种常见的进行性眼部疾病，治疗策略将受益于具有高药物载量和持续递送降眼压药物的纳米颗粒递送系统。已报道脂质体是改善药物角膜低渗透性和生物利用度特性的一种新方法。与此同时，亲水性药物在脂质体制剂中的包封率低仍然是一个主要的制剂挑战。考虑到这一观点，采用两种不同的载药方法（被动载药和远程载药方法）制备了多佐胺脂质体，并评估了各种制剂变量（脂质与药物比例、胆固醇百分比、药物浓度、冻融循环、TPGS含量以及外部和内部缓冲液摩尔浓度和pH值）对包封率的影响。通过加入更高百分比的胆固醇以及增加总脂质浓度，多佐胺在脂质体内的包封率显著提高。与被动载药技术相比，远程载药方法显示出更高的载药效率。在双层中加入TPGS导致包封率降低；然而，药物释放速率减慢。扫描电子显微镜（SEM）研究证实了颗粒分布均匀，呈表面光滑的球形。总之，在吐温60脂质体制剂中使用磷酸盐梯度法和50%胆固醇可获得最高包封率。
