Advanced spray dried proliposomes of amphotericin B lung surfactant-mimic phospholipid microparticles/nanoparticles as dry powder inhalers for targeted pulmonary drug delivery.
Advanced spray dried proliposomes of amphotericin B lung surfactant-mimic phospholipid microparticles/nanoparticles as dry powder inhalers for targeted pulmonary drug delivery.
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DOI：
10.1016/j.pupt.2020.101975
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发表时间：
2020-10
影响因子：
3.2
通讯作者：
Mansour HM
中科院分区：
文献类型：
--
作者：
Gomez AI;Acosta MF;Muralidharan P;Yuan JX;Black SM;Hayes D Jr;Mansour HM
本研究的目的是设计、开发和表征两性霉素B（AmB）与合成磷脂、二棕榈酰磷脂酰胆碱（DPPC）和二棕榈酰磷脂酰甘油（DPPG）（肺表面活性剂模拟磷脂）的可吸入前体脂质体微粒/纳米粒。使用先进的封闭模式系统和高性能旋风分离器对AmB和磷脂的有机溶液进行共喷雾干燥。采用扫描电子显微镜（SEM）观察表面结构、形态和粒径。通过卡尔费休库仑滴定法（KFT）定量前体脂质体的残留水含量。通过X射线粉末衍射（XRPD）测量结晶度/非结晶度。通过差示扫描量热法测量相行为。采用衰减全反射（ATR）-傅里叶变换红外（FTIR）光谱法建立了分子指纹图谱的化学组成。使用UV-VIS光谱法定量加载到前体脂质体中的AmB的量。使用FDA批准的下一代撞击器（NGI）和人干粉吸入器（DPI）（Handihaler®）进行体外气雾剂分散性能。采用不同的人肺细胞系证明体外安全性与剂量和制剂的关系。在中等和高喷雾干燥泵速下形成光滑的球形微粒/纳米颗粒，并且具有低的残留水含量。XRPD衍射图中的特征峰以及DSC中的吸热证实了DPPC/DPPG前体脂质体系统中存在脂质双层结构特征。利用工程化微粒/纳米颗粒实现了上级体外气雾剂性能，证明了作为可吸入干粉的靶向肺部药物递送的适用性。体外细胞研究表明，配制的前体脂质体是安全的。这些AmB前体脂质体可以是一个更好的选择，为严重的肺部真菌感染的靶向治疗。
The purpose of this study was to design, develop and characterize inhalable proliposomal microparticles/nanoparticles of Amphotericin B (AmB) with synthetic phospholipids, dipalmitoylphosphatidylcholine (DPPC) and dipalmitoylphosphatidylglycerol (DPPG) which are lung surfactant-mimic phospholipids. Organic solutions of AmB and phospholipids, were co-spray dried using an advanced closed-mode system and a high performance cyclone. Scanning electron microscopy (SEM) was employed to visualize the surface structure, morphology, and particles size. The residual water content of the proliposomes was quantified by Karl Fisher coulometric titration (KFT). Degree of crystallinity/non-crystallinity was measured by X-ray powder diffraction (XRPD). Phase behavior was measured by differential scanning calorimetry. The chemical composition by molecular fingerprinting was established using attenuated total reflectance (ATR)-Fourier-transform infrared (FTIR) spectroscopy. The amount of AmB loaded into the proliposomes was quantified using UV-VIS spectroscopy. The in vitro aerosol dispersion performance was conducted using the Next Generation Impactor (NGI) and the human dry powder inhaler (DPI) (Handihaler®) that is FDA-approved. Different human lung cell lines were employed to demonstrate in vitro safety as a function of dose and formulation. Smooth, spherical microparticles/nanoparticles were formed at medium and high spray drying pump rates and had low residual water content. A characteristic peak in the XRPD diffraction pattern as well as an endotherm in DSC confirmed the presence of the lipid bilayer structure characteristic in the DPPC/DPPG proliposomal systems. Superior in vitro aerosol performance was achieved with engineered microparticles/nanoparticles demonstrating suitability for targeted pulmonary drug delivery as inhalable dry powders. The in vitro cellular studies demonstrated that the formulated proliposomes are safe. These AmB proliposomes can be a better option for targeted treatment of severe pulmonary fungal infections.
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影响因子：
8
作者：
Duan, Jinghua;Vogt, Frederick G.;Mansour, Heidi M.
通讯作者：
Mansour, Heidi M.
影响因子：
4.6
作者：
Li, Xiaojian;Vogt, Frederick G.;Mansour, Heidi M.
通讯作者：
Mansour, Heidi M.
影响因子：
3.1
作者：
Acosta, Maria F.;Muralidharan, Priya;Mansour, Heidi M.
通讯作者：
Mansour, Heidi M.
影响因子：
3.8
作者：
SCHWARTZMAN, G;ASHER, I;TAYLOR, J
通讯作者：
TAYLOR, J
影响因子：
3.1
作者：
Thakkar, Sachin G.;Fathe, Kristin;Smyth, Hugh D. C.
通讯作者：
Smyth, Hugh D. C.