Design of Gadoteridol-Loaded Cationic Liposomal Adjuvant CAF01 for MRI of Lung Deposition of Intrapulmonary Administered Particles.
Design of Gadoteridol-Loaded Cationic Liposomal Adjuvant CAF01 for MRI of Lung Deposition of Intrapulmonary Administered Particles.
复制标题
用于肺内给药颗粒肺沉积 MRI 的负载钆特醇的阳离子脂质体佐剂 CAF01 的设计。
DOI：
10.1021/acs.molpharmaceut.9b00908
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发表时间：
2019
影响因子：
4.9
通讯作者：
Thakur A
中科院分区：
文献类型：
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作者：
Thakur A
设计有效和安全的吸入性结核病亚单位疫苗需要确定适当的抗原和佐剂，并确定肺部的特定靶标区域。磁共振成像（MRI）可以实现高空间分辨率，但肺的实时解剖和功能MRI具有挑战性。在这里，我们描述了一种新型的gadoteridol负载阳离子佐剂制剂01 （CAF01）的设计，用于mri引导疫苗递送临床测试的TB亚单位候选疫苗H56/CAF01。通过使用质量设计方法来设计负载gadoteridol的CAF01脂质体，以(i)增加对控制gadoteridol负载的配方因素的机制理解，（ii）最大化CAF01中的gadoteridol负载，这一点已通过冷冻透射电镜证实。由于加多特idol与阳离子脂质组分之间存在强烈的吸引静电相互作用，因此加多特idol的包封效率和负载高度依赖于缓冲液pH。在小鼠肺内给药时，最佳加多啶醇负载CAF01脂质体显示出良好的体内稳定性和安全性，同时产生1.5倍的MRI信号增强，并伴有约30%的t1松弛变化。这种配方原理和成像方法可以潜在地用于其他基于粘膜纳米颗粒的配方、种类和肺部病变，这可以很容易地转化为临床应用。
Designing effective and safe tuberculosis (TB) subunit vaccines for inhalation requires identification of appropriate antigens and adjuvants and definition of the specific areas to target in the lungs. Magnetic resonance imaging (MRI) enables high spatial resolution, but real-time anatomical and functional MRI of lungs is challenging. Here, we describe the design of a novel gadoteridol-loaded cationic adjuvant formulation 01 (CAF01) for MRI-guided vaccine delivery of the clinically tested TB subunit vaccine candidate H56/CAF01. Gadoteridol-loaded CAF01 liposomes were engineered by using a quality-by-design approach to (i) increase the mechanistic understanding of formulation factors governing the loading of gadoteridol and (ii) maximize the loading of gadoteridol in CAF01, which was confirmed by cryotransmission electron microscopy. The encapsulation efficiency and loading of gadoteridol were highly dependent on the buffer pH due to strong attractive electrostatic interactions between gadoteridol and the cationic lipid component. Optimal gadoteridol loading of CAF01 liposomes showed good in vivo stability and safety upon intrapulmonary administration into mice while generating 1.5-fold MRI signal enhancement associated with approximately 30%T1relaxation change. This formulation principle and imaging approach can potentially be used for other mucosal nanoparticle-based formulations, species, and lung pathologies, which can readily be translated for clinical use.