用于光触发药物释放的载吲哚菁绿脂质体
Indocyanine Green-Loaded Liposomes for Light-Triggered Drug Release.
作者信息
Lajunen Tatu, Kontturi Leena-Stiina, Viitala Lauri, Manna Moutusi, Cramariuc Oana, Róg Tomasz, Bunker Alex, Laaksonen Timo, Viitala Tapani, Murtomäki Lasse, Urtti Arto
机构信息
Centre for Drug Research, Division of Pharmaceutical Biosciences, University of Helsinki , P.O. Box 56, FI-00014 Helsinki, Finland.
Department of Pharmaceutics, Utrecht Institute of Pharmaceutical Sciences (UIPS), Utrecht University , Universiteitsweg 99, 3584 CG Utrecht, The Netherlands.
出版信息
Mol Pharm. 2016 Jun 6;13(6):2095-107. doi: 10.1021/acs.molpharmaceut.6b00207. Epub 2016 Apr 29.
Light-triggered drug delivery systems enable site-specific and time-controlled drug release. In previous work, we have achieved this with liposomes containing gold nanoparticles in the aqueous core. Gold nanoparticles absorb near-infrared light and release the energy as heat that increases the permeability of the liposomal bilayer, thus releasing the contents of the liposome. In this work, we replaced the gold nanoparticles with the clinically approved imaging agent indocyanine green (ICG). The ICG liposomes were stable at storage conditions (4-22 °C) and at body temperature, and fast near-infrared (IR) light-triggered drug release was achieved with optimized phospholipid composition and a 1:50 ICG-to-lipid molar ratio. Encapsulated small molecular calcein and FITC-dextran (up to 20 kDa) were completely released from the liposomes after light exposure for 15 s. Location of ICG in the PEG layer of the liposomes was simulated with molecular dynamics. ICG has important benefits as a light-triggering agent in liposomes: fast content release, improved stability, improved possibility of liposomal size control, regulatory approval to use in humans, and the possibility of imaging the in vivo location of the liposomes based on the fluorescence of ICG. Near-infrared light used as a triggering mechanism has good tissue penetration and safety. Thus, ICG liposomes are an attractive option for light-controlled and efficient delivery of small and large drug molecules.
光触发药物递送系统能够实现药物的定点和定时释放。在之前的工作中,我们通过在水相核心中含有金纳米颗粒的脂质体实现了这一点。金纳米颗粒吸收近红外光并将能量以热量的形式释放出来,从而增加脂质体双层膜的通透性,进而释放脂质体的内容物。在这项工作中,我们用临床批准的成像剂吲哚菁绿(ICG)取代了金纳米颗粒。ICG脂质体在储存条件(4-22°C)和体温下均稳定,通过优化磷脂组成和1:50的ICG与脂质摩尔比实现了快速近红外(IR)光触发药物释放。暴露于光15秒后,封装的小分子钙黄绿素和FITC-葡聚糖(高达20 kDa)从脂质体中完全释放出来。用分子动力学模拟了ICG在脂质体PEG层中的位置。ICG作为脂质体中的光触发剂具有重要优势:内容物快速释放、稳定性提高、脂质体尺寸控制的可能性增加、已获人体使用的监管批准以及基于ICG荧光对脂质体在体内位置进行成像的可能性。用作触发机制的近红外光具有良好的组织穿透性和安全性。因此,ICG脂质体是光控高效递送小分子和大分子药物的一个有吸引力的选择。