2024-12-18 作者：ws 来源：文献：
Topical anesthetic and pain relief using penetration enhancer and transcriptional transactivator peptide multi-decorated nanostructured lipid carriers
文献链接：
https://www.tandfonline.com/doi/full/10.1080/10717544.2021.1889717作者：
Tao Jiang, Shuangshuang Ma, Yangyang Shen, Yuwen Li, Ruirui Pan &Huaixin Xing
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原文摘要：
Many strategies have been developed to overcome the stratum corneum (SC) barrier, including functionalized nanostructures. Chemical penetration enhancers (CPEs) and cell-penetrating peptides (CPP) were applied to decorate nanostructured lipid carriers (NLC) for topical anesthetic and pain relief. A novel pyrenebutyrate (PB-PEG-DSPE) compound was synthesized by the amide action of the carboxylic acid group of PB with the amido groups of DSPE-PEG. PB-PEG-DSPE has a hydrophobic group, hydrophilic group, and lipid group. The lipid group can be inserted into NLC to form PB functional NLC. In order to improve the penetrability, TAT and PB multi-decorated NLC were designed for the delivery of lidocaine hydrochloride (LID) (TAT/PB LID NLC). The therapeutic effects of NLC in terms of in vitro skin penetration and in vivo in animal models were further studied. The size of TAT/PB LID NLC tested by DLS was 153.6 ± 4.3 nm. However, the size of undecorated LID NLC was 115.3 ± 3.6 nm. The PDI values of NLC vary from 0.13 ± 0.01 to 0.16 ± 0.03. Zeta potentials of NLC were negative, between 20.7 and ability than PB LID NLC (610.7 ± 22.1 29.3 mV. TAT/PB LID NLC (851.2 ± 25.3 mg/cm mg/cm2), TAT LID NLC (551.9 ± 21.82) showed remarkably better percutaneous penetration mg/cm2) (p < .05) and nonmodified LID NLC (428.2 ± 21.4 mg/cm2). TAT/PB LID NLC exhibited the most prominent anesthetic effect than single ligand decorated or undecorated LID NLC in vivo. The resulting TAT/PB LID NLC exhibited good skin penetration and anesthetic efficiency, which could be applied as a promising anesthesia system.
TAT 是一种细胞穿透肽，来源于 HIV - 1 病poison的转录激活因子。它具有氨基酸序列，能够帮助与之相连的分子穿透细胞膜进入细胞内部。TAT 肽段通常包含多个带正电荷的氨基酸，如精氨酸和赖氨酸，这些正电荷使得 TAT 可以与细胞膜表面带负电荷的成分相互作用，从而促进细胞摄取。PEG（聚乙二醇）是一种具有良好生物相容性和水溶性的聚合物。在 TAT - PEG - DSPE 中，PEG 起到连接 TAT 和 DSPE 的作用。其主要作用是增加分子的亲水性，减少非特异性蛋白吸附，并且可以调节分子的大小和空间构象。DSPE 是一种磷脂，其结构特点是有亲水性的磷酸乙醇胺头部和两条疏水性的硬脂酰脂肪酸链。这种结构使 DSPE 在脂质体等纳米载体的构建中发挥关键作用。DSPE 可以与其他磷脂一起形成脂质双层结构，模拟细胞膜的磷脂双分子层。基于TAT-PEG-DSPE的相关特性，制备流程如下：
图：产品方案图及电镜图
采用溶剂扩散技术制备LID负载NLC（LID NLC）。油相：将GMS、ATO和MiglyolVR 812混合，加热，得到油相；用DMF溶解LID、PEG-DSPE和ISL并与油相混合。同时，将Pluronic 68（P68）分散在超纯水中，形成水溶液。以一定的速度搅拌水相，然后快速注入油相。通过与PBS混合物透析获得LID NLC。单个TAT或PB装饰，LID加载NLC（TATLIDLIDNLC或PB LID NLC）采用相同的方法生产，使用PB-PEG-DSPE或TAT-PEG-DSPE，而不是PEG-DSPE。TAT和PB多装饰、LID负载NLC是通过类似的程序产生的，使用PB-PEG-DSPE+TAT-PEG-DSPE，而不是PEG-DSPE。空白TAT和PB多装饰NLC（TAT/PB NLC）采用相同的方法生产，不添加LID。
图：对照曲线
结论：
该文献成功制备出了经TAT-PEG-DSPE修饰的TAT/PB LID NLC。结果证明，TAT/PB LID NLC在体内的麻醉效果比单个配体修饰或未修饰的LID NLC效果好。所得到的TAT/PB LID NLC具有良好的皮肤穿透性和麻醉效率，可作为一种有前途的麻醉系统。
