Purpose

Incorporating fatty acids into the phospholipid bilayer affects membrane packing order and permeability. We recently demonstrated that incorporating triglyceride into liposomes may alter membrane packing order and hydrophobic drug encapsulation capacity. This work investigated the effect of the saturated fatty acid-based triglyceride incorporation into liposomes carrying hydrophilic drugs.

Methods

Effects of tricaprin (TC) incorporation on the physicochemical properties of 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC)-based liposomes encapsulated with small or large hydrophilic model drugs were investigated in terms of dithionite permeability, phase transition temperature, drug encapsulation efficiency, drug release rate, storage stability and cellular uptake of liposomes.

Results

TC incorporation into liposomes decreased dithionite permeability and raised phase transition temperatures of DMPC, indicating TC reduced membrane permeability. TC-induced thermogram changes in small hydrophilic drug model fluorescein-5-(and-6)-sulfonic acid (5-FSA)-encapsulated liposomes were comparable to those in drug-free/TC-incorporated liposomes. In contrast, they were significantly altered in large hydrophilic drug model FITC-BSA-encapsulated liposomes, suggesting macromolecule-induced membrane rearrangement. TC decreased the release rate of 5-FSA but increased that of FITC-BSA. Further, TC improved 5-FSA-encapsulated liposomes’ storage and freeze-drying stability. TC incorporation did not affect the cellular uptake of 5-FSA encapsulated in liposomes.

Conclusion

Our work demonstrates that saturated fatty acid-based triglyceride incorporation provides multiple benefits for liposomes carrying small, but not large, hydrophilic drugs by improving membrane properties.

中文翻译：

---

三癸酸酯作为膜通透性调节剂：从脂质体中持续释放小的亲水性物质

目的

将脂肪酸掺入磷脂双层会影响膜堆积顺序和渗透性。我们最近证明，将甘油三酯掺入脂质体可能会改变膜包装顺序和疏水性药物包封能力。这项工作调查了基于饱和脂肪酸的甘油三酯掺入到携带亲水性药物的脂质体中的效果。

方法

三癸酸酯 (TC) 掺入对 1,2-二肉豆蔻酰基-sn-甘油-3-磷酸胆碱 (DMPC) 基脂质体的理化性质的影响在连二亚硫酸盐渗透性、相变温度方面进行了研究、药物包封效率、药物释放速率、储存稳定性和脂质体的细胞摄取。

结果

将 TC 掺入脂质体可降低连二亚硫酸盐的通透性并提高 DMPC 的相变温度，表明 TC 降低了膜通透性。小亲水性药物模型荧光素-5-（和-6）-磺酸（5-FSA）封装的脂质体中 TC 诱导的热谱图变化与无药物/TC 掺入脂质体中的变化相当。相反，它们在大的亲水性药物模型 FITC-BSA 封装的脂质体中发生了显着改变，表明大分子诱导的膜重排。TC 降低了 5-FSA 的释放速率，但增加了 FITC-BSA 的释放速率。此外，TC 改善了 5-FSA 封装的脂质体的储存和冷冻干燥稳定性。TC 掺入不影响封装在脂质体中的 5-FSA 的细胞摄取。

结论

我们的工作表明，基于饱和脂肪酸的甘油三酯掺入通过改善膜特性为携带小而不是大的亲水性药物的脂质体提供了多种好处。