坚固的阳离子光激活热敏脂质体的开发：选择合适的脂质,Molecular Pharmaceutics

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坚固的阳离子光激活热敏脂质体的开发：选择合适的脂质
Molecular Pharmaceutics ( IF 4.5 ) Pub Date : 2023-10-24 , DOI: 10.1021/acs.molpharmaceut.3c00602
Puja Gangurde ₁ , Mohammad Mahmoudzadeh ₁ , Zahra Gounani ₁ , Artturi Koivuniemi ₁ , Patrick Laurén ₁ , Tatu Lajunen _{1,

2} , Timo Laaksonen _{1,

3}

Affiliation

人们对阳离子光激活热敏脂质体（CLTSL）作为位点特异性和受控药物释放的手段进行了广泛的研究；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稳定和响应系统的发展至关重要。在这项研究中，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。掺入聚乙二醇 PEG 分子可形成具有低多分散指数的均匀脂质体，而添加不饱和脂质 (DOTAP) 则可形成极度渗漏的脂质体，在体温下孵育 10 分钟即可释放近 80%。相反，在配方中加入胆固醇会过多地增加脂质体的稳定性，并降低其对刺激响应释放的敏感性，光照射 2 分钟后仅释放 14%。为了实现稳定且功能性的 CLTSL，我们用饱和脂质 (DPTAP) 替代等量的不饱和脂质，从而形成对光高度响应的稳定脂质体，在光照 10 秒内释放其 90% 的含量。我们还使用具有饱和和不饱和脂质的脂质组合物进行了两次原子分子动力学模拟，以研究脂质组合物对脂质体脂质双层动力学特性的影响。我们的研究结果表明，用于制备脂质体的脂质的性质显着影响其特性，特别是当药物负载需要稳定但同时需要触发药物释放特性时。因此，选择正确数量的适当脂质对于制备具有所需特性的脂质体至关重要。

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Development of Robust Cationic Light-Activated Thermosensitive Liposomes: Choosing the Right Lipids

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.

更新日期：2023-10-24

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