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Self-Emulsifying Drug Delivery Systems: Hydrophobic Drug Polymer Complexes Provide a Sustained Release in Vitro.
Molecular Pharmaceutics ( IF 4.9 ) Pub Date : 2020-08-25 , DOI: 10.1021/acs.molpharmaceut.0c00389
Ahmad Malkawi 1 , Aamir Jalil 1 , Imran Nazir 1, 2 , Barbara Matuszczak 3 , Ross Kennedy 4 , Andreas Bernkop-Schnürch 1
Affiliation  

The aim of this study was to develop hydrophobic ionic drug polymer complexes in order to provide sustained drug release from self-emulsifying drug delivery systems (SEDDS). Captopril (CTL) was used as an anionic model drug to form ionic complexes with the cationic polymers Eudragit RS, RL, and E. Complexes of polymer to CTL charge ratio 1:1, 2:1, and 4:1 were incorporated in two SEDDS, namely FA which was 40% Kolliphor RH 40, 20% Kolliphor EL, and 40% castor oil and FB, which was 40% Kolliphor RH 40, 30% glycerol, 15% Kolliphor EL, and 15% castor oil. Blank and complex loaded SEDDS were characterized regarding their droplet size, polydispersity index (PDI), and zeta potential. Resazurin assay was performed on Caco-2 cells to evaluate the biocompatibility of SEDDS. Release of CTL from SEDDS was determined in release medium containing 0.2 mg/mL of 5,5′-dithiobis(2-nitrobenzoic acid) (DNTB) allowing quantification of free drug released into solution via a thiol/disulfide exchange reaction between CTL and DNTB forming a yellow dye. The droplet size of SEDDS FA and SEDDS FB were in the range of 100 ± 20 nm and 40 ± 10 nm, respectively, with a PDI < 0.5. The zeta potential of SEDDS FA and SEDDS FB increased after the incorporation of complexes. Cell viability remained above 80% after incubation with SEDDS FA and SEDDS FB in a concentration of 1% and 3% for 4 h. Without any polymer, CTL was entirely released from both SEDDS within seconds. In contrast, the higher the cationic lipophilic polymer to CTL ratio in SEDDS, the more sustained was the release of CTL. Among the polymers which were evaluated, Eudragit RL provided the most sustained release. SEDDS FA containing Eudragit RL and CTL in a ratio of 1:1 released 64.78 ± 8.28% of CTL, whereas SEDDS FB containing the same complex showed a release of 91.85 ± 1.17% within 1 h. Due to the formation of lipophilic ionic polymer complexes a sustained drug release from oily droplets formed by SEDDS can be achieved. Taking into account that drugs are otherwise instantly released from SEDDS, results of this study might open the door for numerous additional applications of SEDDS for which a sustained drug release is essential.

中文翻译:

自乳化给药系统:疏水性药物聚合物复合物在体外提供持续释放。

本研究的目的是开发疏水性离子药物聚合物复合物,以便从自乳化药物递送系统 (SEDDS) 中持续释放药物。卡托普利 (CTL) 用作阴离子模型药物,与阳离子聚合物 Eudragit RS、RL 和 E 形成离子复合物。聚合物与 CTL 电荷比为 1:1、2:1 和 4:1 的复合物分为两种SEDDS,即 FA,即 40% Kolliphor RH 40、20% Kolliphor EL 和 40% 蓖麻油和 FB,即 40% Kolliphor RH 40、30% 甘油、15% Kolliphor EL 和 15% 蓖麻油。空白和复合负载 SEDDS 的特征在于它们的液滴大小、多分散指数 (PDI) 和 zeta 电位。对 Caco-2 细胞进行刃天青测定以评估 SEDDS 的生物相容性。CTL 从 SEDDS 中的释放是在含有 0. 2 mg/mL 的 5,5'-二硫代双(2-硝基苯甲酸)(DNTB)允许量化通过 CTL 和 DNTB 之间的硫醇/二硫化物交换反应释放到溶液中的游离药物,形成黄色染料。SEDDS FA 和 SEDDS FB 的液滴尺寸分别在 100 ± 20 nm 和 40 ± 10 nm 的范围内,PDI < 0.5。SEDDS FA 和 SEDDS FB 的 zeta 电位在掺入复合物后增加。与浓度为 1% 和 3% 的 SEDDS FA 和 SEDDS FB 孵育 4 小时后,细胞活力仍保持在 80% 以上。在没有任何聚合物的情况下,CTL 在几秒钟内从两个 SEDDS 中完全释放出来。相比之下,SEDDS 中阳离子亲脂聚合物与 CTL 的比率越高,CTL 的释放就越持续。在评估的聚合物中,Eudragit RL 提供了最持续的释放。含有 Eudragit RL 和 CTL 比例为 1:1 的 SEDDS FA 释放了 64.78 ± 8.28% 的 CTL,而含有相同复合物的 SEDDS FB 在 1 小时内释放了 91.85 ± 1.17%。由于亲脂性离子聚合物复合物的形成,可以实现从 SEDDS 形成的油滴中持续释放药物。考虑到药物会立即从 SEDDS 中释放出来,这项研究的结果可能为 SEDDS 的许多其他应用打开了大门,对于这些应用,持续的药物释放是必不可少的。
更新日期:2020-10-05
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