Musa Muhammad Nuh, David Sheba Rani, Zulkipli Ihsan Nazurah, Mahadi Abdul Hanif, Chakravarthi Srikumar, Rajabalaya Rajan
PAPRSB Institute of Health Sciences, Universiti Brunei Darussalam, Bandar Seri Begawan BE 1410, Brunei Darussalam.
Centre for Advanced Material and Energy Sciences (CAMES), Universiti Brunei Darussalam, Bandar Seri Begawan BE 1410, Brunei Darussalam.
Bioimpacts. 2017;7(4):227-239. doi: 10.15171/bi.2017.27. Epub 2017 Sep 3.
The use of liquid crystalline (LC) gel formulations for drug delivery has considerably improved the current delivery methods in terms of bioavailability and efficacy. The purpose of this study was to develop and evaluate LC gel formulations to deliver the anti-cancer drug exemestane through transdermal route. Two LC gel formulations were prepared by phase separation coacervation method using glyceryl monooleate (GMO), Tween 80 and Pluronic® F127 (F127). The formulations were characterized with regard to encapsulation efficiency (EE), vesicle size, Fourier transform infrared (FTIR) spectroscopy, surface morphology (using light and fluorescence microscopy), in vitro release, ex vivo permeation, in vitro effectiveness test on MDA-MB231 cancer cell lines and histopathological analysis. Results exhibited that the EE was 85%-92%, vesicle size was 119.9-466.2 nm while morphology showed spherical vesicles after hydration. An FTIR result also revealed that there was no significant shift in peaks corresponding to Exemestane and excipients. LC formulations release the drug from cellulose acetate and Strat-MTM membrane from 15%-88.95%, whereas ex vivo permeation ranges from 37.09-63%. The in vitro effectiveness study indicated that even at low exemestane concentrations (12.5 and 25 μg/mL) the formulations were able to induce cancer cell death, regardless of the surfactant used. Histopathological analysis thinning of the epidermis as the formulations penetrate into the intercellular regions of squamous cells. The results conjectured that exemestane could be incorporated into LC gels for the transdermal delivery system and further preclinical studies such as pharmacokinetic and pharmacodynamic studies will be carried out with suitable animal models.
用于药物递送的液晶（LC）凝胶制剂在生物利用度和疗效方面极大地改进了当前的递送方法。本研究的目的是开发和评估通过经皮途径递送抗癌药物依西美坦的LC凝胶制剂。使用单油酸甘油酯（GMO）、吐温80和普朗尼克®F127（F127）通过相分离凝聚法制备了两种LC凝胶制剂。对制剂进行了包封率（EE）、囊泡大小、傅里叶变换红外（FTIR）光谱、表面形态（使用光学和荧光显微镜）、体外释放、离体渗透、对MDA-MB231癌细胞系的体外有效性测试以及组织病理学分析等方面的表征。结果显示，包封率为85%-92%，囊泡大小为119.9-466.2 nm，水化后形态显示为球形囊泡。FTIR结果还表明，与依西美坦和辅料相对应的峰没有明显位移。LC制剂从醋酸纤维素和Strat-MTM膜释放药物的比例为15%-88.95%，而离体渗透范围为37.09%-63%。体外有效性研究表明，即使在低依西美坦浓度（12.5和25μg/mL）下，无论使用何种表面活性剂，制剂都能够诱导癌细胞死亡。组织病理学分析表明，随着制剂渗透到鳞状细胞的细胞间区域，表皮变薄。结果推测，依西美坦可以被纳入用于经皮递送系统的LC凝胶中，并将使用合适的动物模型进行进一步的临床前研究，如药代动力学和药效学研究。
