Methyl-Branched Liposomes as a Depot for Sustained Drug Delivery.
Methyl-Branched Liposomes as a Depot for Sustained Drug Delivery.
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甲基支化脂质体作为持续药物递送的储存库。
DOI：
10.1021/acs.nanolett.3c02137
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发表时间：
2023
期刊：
影响因子：
10.8
通讯作者：
Kohane,DanielS
中科院分区：
文献类型：
--
作者：
Li,Yang;Shao,Rachelle;Ostertag-Hill,ClaireA;Torre,Matthew;Yan,Ran;Kohane,DanielS
药量不足和药量泄漏控制限制了脂质体药物载体作用的持续时间，并可能引起毒性。在这里，我们报告了一种脂质体系统作为持续药物递送的仓库，其设计灵感来自古菌膜对质子和溶质的低渗透性。在脂质双分子层中加入甲基支链磷脂可以减少有效载荷在脂质体膜上的扩散，从而使药物负载能力提高10-16%，使小分子在前24小时的释放减少40-48%。通过坐骨神经注射证实了这种入路的体内影响。包裹麻醉河豚毒素（TTX）的甲基支链脂质体可以显著延长局部麻醉时间，达到70小时，而含有常规脂质的脂质体只能达到16小时。目前的工作证明了甲基支链脂质体的有用性，以增强脂质体储存系统的持续药物输送。
Inadequate drug loading and control of payload leakage limit the duration of the effect of liposomal drug carriers and may cause toxicity. Here, we report a liposome system as a depot for sustained drug delivery whose design is inspired by the low permeability of Archaeal membranes to protons and solutes. Incorporating methyl-branched phospholipids into lipid bilayers decreased payload diffusion across liposomal membranes, thereby enhancing the drug load capacity by 10–16% and reducing the release of small molecules in the first 24 h by 40–48%. The in vivo impact of this approach was demonstrated by injection at the sciatic nerve. Methyl-branched liposomes encapsulating the anesthetic tetrodotoxin (TTX) achieved markedly prolonged local anesthesia lasting up to 70 h, in comparison to the 16 h achieved with liposomes containing conventional lipids. The present work demonstrates the usefulness of methyl-branched liposomes to enhance liposomal depot systems for sustained drug delivery.