Islam Md Rafiqul, Chowdhury Md Raihan, Wakabayashi Rie, Kamiya Noriho, Moniruzzaman Muhammad, Goto Masahiro
Department of Applied Chemistry, Graduate School of Engineering, Kyushu University, 744 Motooka, Nishi-ku, Fukuoka 819-0395, Japan.
Department of Applied Chemistry and Chemical Engineering, Noakhali Science and Technology University, Noakhali 3814, Bangladesh.
Pharmaceutics. 2020 Apr 24;12(4):392. doi: 10.3390/pharmaceutics12040392.
The transdermal delivery of sparingly soluble drugs is challenging due to of the need for a drug carrier. In the past few decades, ionic liquid (IL)-in-oil microemulsions (IL/O MEs) have been developed as potential carriers. By focusing on biocompatibility, we report on an IL/O ME that is designed to enhance the solubility and transdermal delivery of the sparingly soluble drug, acyclovir. The prepared MEs were composed of a hydrophilic IL (choline formate, choline lactate, or choline propionate) as the non-aqueous polar phase and a surface-active IL (choline oleate) as the surfactant in combination with sorbitan laurate in a continuous oil phase. The selected ILs were all biologically active ions. Optimized pseudo ternary phase diagrams indicated the MEs formed thermodynamically stable, spherically shaped, and nano-sized (<100 nm) droplets. An in vitro drug permeation study, using pig skin, showed the significantly enhanced permeation of acyclovir using the ME. A Fourier transform infrared spectroscopy study showed a reduction of the skin barrier function with the ME. Finally, a skin irritation study showed a high cell survival rate (>90%) with the ME compared with Dulbecco's phosphate-buffered saline, indicates the biocompatibility of the ME. Therefore, we conclude that IL/O ME may be a promising nano-carrier for the transdermal delivery of sparingly soluble drugs.
由于需要药物载体，难溶性药物的经皮给药具有挑战性。在过去几十年中，油包离子液体（IL）微乳液（IL/O MEs）已被开发为潜在的载体。通过关注生物相容性，我们报道了一种旨在提高难溶性药物阿昔洛韦的溶解度和经皮给药的IL/O ME。制备的MEs由亲水性离子液体（甲酸胆碱、乳酸胆碱或丙酸胆碱）作为非水极性相和表面活性离子液体（油酸胆碱）作为表面活性剂，与月桂醇山梨坦在连续油相中组合而成。所选的离子液体都是生物活性离子。优化的伪三元相图表明，MEs形成了热力学稳定、球形且纳米尺寸（<100 nm）的液滴。使用猪皮进行的体外药物渗透研究表明，使用MEs时阿昔洛韦的渗透显著增强。傅里叶变换红外光谱研究表明，MEs可降低皮肤屏障功能。最后，皮肤刺激性研究表明，与杜尔贝科磷酸盐缓冲盐水相比，MEs具有较高的细胞存活率（>90%），表明MEs具有生物相容性。因此，我们得出结论，IL/O ME可能是难溶性药物经皮给药的一种有前景的纳米载体。
