Integrated Chemical BioPhysics Research, Faculty of Science, University Putra Malaysia (UPM), Serdang, Selangor 43400, Malaysia.
Centre of Foundation Studies for Agricultural Science, University Putra Malaysia (UPM), Serdang, Selangor 43400, Malaysia.
Int J Nanomedicine. 2019 Sep 9;14:7323-7338. doi: 10.2147/IJN.S212635. eCollection 2019.
Gemcitabine (GEM) is a chemotherapeutic agent, which is known to battle cancer but challenging due to its hydrophilic nature. Nanoemulsion is water-in-oil (W/O) nanoemulsion shows potential as a carrier system in delivering gemcitabine to the cancer cell.
The behaviour of GEM in MCT/surfactants/NaCl systems was studied in the ternary system at different ratios of Tween 80 and Span 80. The system with surfactant ratio 3:7 of Tween 80 and Span 80 was chosen for further study on the preparation of nanoemulsion formulation due to the highest isotropic region. Based on the selected ternary phase diagram, a composition of F1 was chosen and used for optimization by using the D-optimal mixture design. The interaction variables between medium chain triglyceride (MCT), surfactant mixture Tween 80: Span 80 (ratio 3:7), 0.9 % sodium chloride solution and gemcitabine were evaluated towards particle size as a response.
The results showed that NaCl solution and GEM gave more effects on particle size, polydispersity index and zeta potential of 141.57±0.05 nm, 0.168 and -37.10 mV, respectively. The optimized nanoemulsion showed good stability (no phase separation) against centrifugation test and storage at three different temperatures. The in vitro release of gemcitabine at different pH buffer solution was evaluated. The results showed the release of GEM in buffer pH 6.5 (45.19%) was higher than GEM in buffer pH 7.4 (13.62%). The cytotoxicity study showed that the optimized nanoemulsion containing GEM induced cytotoxicity towards A549 cell and at the same time reduced cytotoxicity towards MRC5 when compared to the control (GEM solution).
吉西他滨（GEM）是一种化疗药物，已知具有抗癌作用，但由于其亲水性而具有挑战性。纳米乳剂是一种油包水（W/O）纳米乳剂，具有作为载体系统将吉西他滨递送到癌细胞中的潜力。
在不同的 Tween 80 和 Span 80 比例的三元体系中研究了 GEM 在 MCT/表面活性剂/NaCl 系统中的行为。选择表面活性剂比例为 3:7 的 Tween 80 和 Span 80 的系统用于进一步研究纳米乳剂制剂的制备，因为该系统具有最高的各向同性区域。基于所选的三元相图，选择 F1 组成，并通过使用 D-最优混合设计进行优化。评估了中链甘油三酯（MCT）、表面活性剂混合物 Tween 80:Span 80（比例 3:7）、0.9%氯化钠溶液和吉西他滨之间的相互作用变量对粒径的影响。
结果表明，NaCl 溶液和 GEM 对粒径、多分散指数和 Zeta 电位的影响最大，分别为 141.57±0.05nm、0.168 和-37.10mV。优化后的纳米乳剂在离心试验和在三种不同温度下储存时表现出良好的稳定性（无相分离）。在不同 pH 缓冲溶液中评估了吉西他滨的体外释放。结果表明，在 pH 6.5 的缓冲液中（45.19%）释放的 GEM 高于在 pH 7.4 的缓冲液中（13.62%）。细胞毒性研究表明，与对照（GEM 溶液）相比，含有 GEM 的优化纳米乳剂诱导 A549 细胞的细胞毒性，同时降低对 MRC5 的细胞毒性。
