Development of egg PC/cholesterol/α-tocopherol liposomes with ionic gradients to deliver ropivacaine
Development of egg PC/cholesterol/α-tocopherol liposomes with ionic gradients to deliver ropivacaine
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DOI：
10.3109/08982104.2015.1022555
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发表时间：
2016-01-02
影响因子：
4.4
通讯作者：
de Paula, Eneida
中科院分区：
文献类型：
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作者：
Goncalves da Silva, Camila Morais;Fraceto, Leonardo Fernandes;de Paula, Eneida
背景：罗哌卡因 (RVC) 是一种广泛用于外科手术的氨基酰胺局部麻醉剂。将 RVC 封装在脂质体中并与环糊精复合的研究已显示出良好的结果，但为了将 RVC 用于长时间手术和术后期间，需要更长时间的麻醉效果。 目的：因此，本研究旨在使用修饰的脂质体提供延长的 RVC 释放和增加的负载。 材料和方法： 研究了三种类型的囊泡：（i）大多层囊泡（LMV），（ii）大多层囊泡多囊泡 (LMVV) 和 (iii) 大单层囊泡 (LUV)，用鸡蛋磷脂酰胆碱/胆固醇/生育酚 (4:3:0.07mol%) 在 pH 7.4 下制备。制备了离子梯度脂质体（内部：pH 5.5、pH 5.5+(NH4)(2)SO4 和 pH 7.4+(NH4)(2)SO4），与传统脂质体（内部：pH 7.4）相比，其 RVC 负载量有所改善。 结果和讨论：验证了用于 RVC 定量的高效液相色谱分析方法。脂质体的特征包括尺寸、zeta 电位、多分散性、形态、RVC 封装效率 (EE(%)) 和体外 RVC 释放。 LMVV 脂质体提供比 LMV 或 LUV 更好的性能。最佳配方是使用 pH 5.5 (LMVV 5.5(in)) 或 pH 7.4 和 250mM (NH4)(2)SO4 在内水核 (LMVV 7.4(in)+硫酸铵) 中制备而成，能够封装高达 2%的 RVC，具有高吸收（EE(%) 接近 70%）和持续释放（约 25 小时）。结论：将 RVC 封装在离子梯度脂质体中显着延长了麻醉剂的释放持续时间，表明该策略可能是在手术过程中和术后期间促进长期麻醉的可行方法。
Context: Ropivacaine (RVC) is an aminoamide local anesthetic widely used in surgical procedures. Studies with RVC encapsulated in liposomes and complexed in cyclodextrins have shown good results, but in order to use RVC for lengthy procedures and during the postoperative period, a still more prolonged anesthetic effect is required.Objective: This study therefore aimed to provide extended RVC release and increased upload using modified liposomes.Materials and methods: Three types of vesicles were studied: (i) large multilamellar vesicle (LMV), (ii) large multivesicular vesicle (LMVV) and (iii) large unilamellar vesicle (LUV), prepared with egg phosphatidylcholine/cholesterol/-tocopherol (4:3:0.07mol%) at pH 7.4. Ionic gradient liposomes (inside: pH 5.5, pH 5.5+(NH4)(2)SO4 and pH 7.4+(NH4)(2)SO4) were prepared and showed improved RVC loading, compared to conventional liposomes (inside: pH 7.4).Results and discussion: An high-performance liquid chromatography analytical method was validated for RVC quantification. The liposomes were characterized in terms of their size, zeta potential, polydispersion, morphology, RVC encapsulation efficiency (EE(%)) and in vitro RVC release. LMVV liposomes provided better performance than LMV or LUV. The best formulations were prepared using pH 5.5 (LMVV 5.5(in)) or pH 7.4 with 250mM (NH4)(2)SO4 in the inner aqueous core (LMVV 7.4(in)+ammonium sulfate), enabling encapsulation of as much as 2% RVC, with high uptake (EE(%) approximate to 70%) and sustained release (approximate to 25h).Conclusion: The encapsulation of RVC in ionic gradient liposomes significantly extended the duration of release of the anesthetic, showing that this strategy could be a viable means of promoting longer-term anesthesia during surgical procedures and during the postoperative period.