Microencapsulated Solid Lipid Nanoparticles as a Hybrid Platform for Pulmonary Antibiotic Delivery
Microencapsulated Solid Lipid Nanoparticles as a Hybrid Platform for Pulmonary Antibiotic Delivery
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DOI：
10.1021/acs.molpharmaceut.7b00169
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发表时间：
2017-09-01
影响因子：
4.9
通讯作者：
Remunan-Lopez, Carmen
中科院分区：
文献类型：
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作者：
Gaspar, Diana P.;Gaspar, Maria Manuela;Remunan-Lopez, Carmen
含有利福布汀(RFB)的固体脂质纳米粒(SLN)具有肺部给药目的，通过一种避免使用有机溶剂或超声波的技术开发出来。为了促进其肺部给药，使用合适的辅料(甘露醇和海藻糖)，通过喷雾干燥技术将RFB负载的SLN包含在适当大小的微球中。共聚焦显微镜分析表明，微球呈球形，SLN被有效地微囊化并均匀分布在微球基质中。气动直径在到达肺泡区时有一个最佳分布。采用双撞击法对干粉雾化过程中的性能和体外药物沉积进行了测试，证实微球可以到达肺深部。等温滴定热法表明，SLN对甘露醇的亲和力高于对海藻糖的亲和力。微球在水介质中溶解后，SLN很容易被回收，保持了它们的物理化学性质。当这些干燥的粉末到达肺深部时，微球预计会很容易溶解，传递SLN，进而释放RFB。微囊化RFB-SLN在体内的生物分布表明，该抗生素在肺部给药15分钟和30分钟后均能达到受试器官。在小鼠感染结核分枝杆菌H37Rv株的模型中，也评估了它们的抗分枝杆菌活性，与未治疗的动物相比，它们对结核分枝杆菌感染的活性增强。这些结果表明，RFB-SLN微囊化是一种很有前途的治疗结核病的方法。
Solid lipid nanoparticles (SLN) containing rifabutin (RFB), with pulmonary administration purposes, were developed through a technique that avoids the use of organic solvents or sonication. To facilitate their pulmonary delivery, the RFB-loaded SLN were included in microspheres of appropriate size using suitable excipients (mannitol and trehalose) through a spray-drying technique. Confocal analysis microscopy showed that microspheres are spherical and that SLN are efficiently microencapsulated and homogeneously distributed throughout the microsphere matrices. The aerodynamic diameters observed an optimal distribution for reaching the alveolar region. The dry powder's performance during aerosolization and the in vitro drug deposition were tested using a twin-impinger approach, which confirmed that the microspheres can reach the deep lung. Isothermal titration calorimetry revealed that SLN have higher affinity for mannitol than for trehalose. Upon microsphere dissolution in aqueous media, SLN were readily recovered, maintaining their physicochemical properties. When these dry powders reach the deep lung, microspheres are expected to readily dissolve, delivering the SLN which, in turn, will release RFB. The in vivo biodistribution of microencapsulated RFB-SLN demonstrated that the antibiotic achieved the tested organs 15 and 30 min post pulmonary administration. Their antimycobacterial activity was also evaluated in a murine model of infection with a Mycobacterium tuberculosis strain H37Rv resulting in an enhancement of activity against M. tuberculosis infection compared to nontreated animals. These results suggest that RFB-SLN microencapsulation is a promising approach for the treatment of tuberculosis.