Drug Research Program, Division of Pharmaceutical Biosciences, Faculty of Pharmacy, University of Helsinki, Viikinkaari 5 E, FI-00790 Helsinki, Finland.
School of Pharmacy, University of Eastern Finland, P.O. Box 1627, FI-70211 Kuopio, Finland.
Mol Pharm. 2023 Nov 6;20(11):5728-5738. doi: 10.1021/acs.molpharmaceut.3c00602. Epub 2023 Oct 24.
Extensive research has been conducted on cationic light-activated thermosensitive liposomes (CLTSLs) as a means for site-specific and controlled drug release; however, less attention has been given to the stability of these nanoparticles. Selecting the appropriate lipids is crucial for the development of a stable and responsive system. In this study, we investigated the impact of various lipids on the physical properties of cationic light-activated liposomes. Incorporating poly(ethylene glycol) PEG molecules resulted in uniform liposomes with low polydispersity index, while the addition of unsaturated lipid (DOTAP) resulted in extremely leaky liposomes, with almost 80% release in just 10 min of incubation at body temperature. Conversely, the inclusion of cholesterol in the formulation increased liposome stability too much and decreased their sensitivity to stimuli-responsive release, with only 14% release after 2 min of light exposure. To achieve stable and functional CLTSL, we substituted an equivalent amount of unsaturated lipid with a saturated lipid (DPTAP), resulting in stable liposomes at body temperature that were highly responsive to light, releasing 90% of their content in 10 s of light exposure. We also conducted two atomistic molecular dynamics simulations using lipid compositions with saturated and unsaturated lipids to investigate the effect of lipid composition on the dynamical properties of the liposomal lipid bilayer. Our findings suggest that the nature of lipids used to prepare liposomes significantly affects their properties, especially when the drug loading needs to be stable but triggered drug release properties are required at the same time. Selecting the appropriate lipids in the right amount is therefore essential for the preparation of liposomes with desirable properties.
已经有大量研究致力于研究阳离子光激活热敏脂质体（CLTSLs）作为一种实现靶向和控制药物释放的方法；然而，人们对这些纳米颗粒的稳定性关注较少。选择合适的脂质对于开发稳定且响应性的系统至关重要。在本研究中，我们研究了各种脂质对阳离子光激活脂质体物理性质的影响。 引入聚乙二醇（PEG）分子可得到具有低多分散指数的均匀脂质体，而添加不饱和脂质（DOTAP）则会导致脂质体极度渗漏，在体温下孵育 10 分钟后几乎有 80%的药物释放。相反，在配方中加入胆固醇会使脂质体过于稳定，并降低其对刺激响应性释放的敏感性，在光照 2 分钟后仅释放 14%的药物。为了获得稳定且功能化的 CLTSL，我们用饱和脂质（DPTAP）等量替代不饱和脂质，从而在体温下得到稳定的脂质体，对光具有高度响应性，在 10 秒的光照下释放 90%的药物。我们还使用具有饱和和不饱和脂质的脂质组成进行了两次原子分子动力学模拟，以研究脂质组成对脂质双层动态性质的影响。我们的研究结果表明，用于制备脂质体的脂质性质会显著影响其性质，特别是当需要稳定的药物负载但同时需要触发药物释放性质时。因此，选择适量的适当脂质对于制备具有理想性质的脂质体至关重要。
