Akhgari Abbas, Heshmati Zohreh, Afrasiabi Garekani Hadi, Sadeghi Fatemeh, Sabbagh Atena, Sharif Makhmalzadeh Behzad, Nokhodchi Ali
Targeted Drug Delivery Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
Nanotechnology Research Center and School of Pharmacy, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
Colloids Surf B Biointerfaces. 2017 Apr 1;152:29-35. doi: 10.1016/j.colsurfb.2016.12.035. Epub 2016 Dec 23.
Generally, although the conventional drug delivery systems, such as using only pH-dependent polymers or time-dependent release systems are popular, the individuals' variations of physiological conditions usually lead to premature or imperfect drug release from each of these systems. Therefore, a combination of pH- and time-dependent polymers could be more reliable for delivering drugs to the lower GI tract such as colon. To this end, electrospinning method was used as a fabrication approach for preparing electrospun nanofibers of indomethacin aimed for colon delivery. Formulations were prepared based on a 3 full factorial design. Independent variables were the drug:polymer ratio (with the levels of 3:5, 4.5:5 and 6:5w/w) and Eudragit S:Eudragit RS w/w ratio (20:80, 60:40 and 100:0). The evaluated responses were drug release at pH 1.2, 6.4, 6.8 and 7.4. Combinations of Eudragit S (ES), Eudragit RS (ERS) and drug based on factorial design were loaded in 10ml syringes. Electrospinning method was used to prepare electrospun nanofibers from electrospinning solutions. Conductivity and the viscosity of the solutions were analyzed prior to electrospinning. After collection, the nanofibers were evaluated in terms of morphology and drug release. It was shown that the ratio of drug:polymer and polymer:polymer were pivotal factors to control the drug release from nanofibers. A formulation containing Eudragit S:Eudragit RS (60:40) and drug:polymer ratio of 3:5 exhibited the most appropriate drug release as a colon delivery system with a minor release at pH 1.2, 6.4 and 6.8 and major release at pH 7.4. Nanofibers resulted from this formulation were also more uniform and contained fewer amounts of beads. It was demonstrated that the electrospinning could be regarded as a modern approach for the preparation of colon drug delivery systems leading to marketable products.
一般来说，尽管传统的药物递送系统很受欢迎，例如仅使用pH依赖性聚合物或时间依赖性释放系统，但个体生理状况的差异通常会导致药物从这些系统中过早或不完全释放。因此，将pH依赖性和时间依赖性聚合物结合起来，对于将药物递送至结肠等下消化道可能更可靠。为此，采用静电纺丝法作为制备用于结肠递送的吲哚美辛静电纺纳米纤维的制造方法。基于三因素全因子设计制备制剂。自变量为药物与聚合物的比例（水平为3:5、4.5:5和6:5 w/w）以及尤特奇S与尤特奇RS的w/w比例（20:80、60:40和100:0）。评估的响应为在pH 1.2、6.4、6.8和7.4时的药物释放。基于因子设计的尤特奇S（ES）、尤特奇RS（ERS）和药物的组合被装入10毫升注射器中。使用静电纺丝法从静电纺丝溶液中制备静电纺纳米纤维。在静电纺丝之前分析溶液的电导率和粘度。收集后，对纳米纤维的形态和药物释放进行评估。结果表明，药物与聚合物的比例以及聚合物与聚合物的比例是控制纳米纤维药物释放的关键因素。含有尤特奇S:尤特奇RS（60:40）且药物与聚合物比例为3:5的制剂作为结肠递送系统表现出最合适的药物释放，在pH 1.2、6.4和6.8时释放较少，在pH 7.4时释放较多。该制剂产生的纳米纤维也更均匀，且含有的珠粒数量更少。结果表明，静电纺丝可被视为一种制备结肠药物递送系统的现代方法，有望生产出适销产品。
