Design, characterization, and aerosolization of organic solution advanced spray-dried moxifloxacin and ofloxacin dipalmitoylphosphatidylcholine (DPPC) microparticulate/nanoparticulate powders for pulmonary inhalation aerosol delivery
Design, characterization, and aerosolization of organic solution advanced spray-dried moxifloxacin and ofloxacin dipalmitoylphosphatidylcholine (DPPC) microparticulate/nanoparticulate powders for pulmonary inhalation aerosol delivery
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DOI：
10.2147/ijn.s48631
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发表时间：
2013-01-01
影响因子：
8
通讯作者：
Mansour, Heidi M.
中科院分区：
文献类型：
--
作者：
Duan, Jinghua;Vogt, Frederick G.;Mansour, Heidi M.
本研究的目的是设计和开发可吸入的抗生素盐酸莫西沙星（MOXI）和氧氟沙星（OFLX）微粒和纳米粒以及多功能抗生素微粒（含或不含肺表面活性剂1，2-二棕榈酰-sn-甘油-3-磷酸胆碱（DPPC））作为肺部纳米药物用于靶向干粉吸入给药。通过先进的喷雾干燥颗粒工程，从稀溶液中以封闭模式（无水）从有机溶液中合理设计和生产颗粒。扫描电子显微镜显示，这些粒子具有最佳的粒子形态和表面形态，并且粒径分布适合于肺部递送。全面和系统的理化表征和体外气雾剂分散性能显示，这两种氟喹诺酮类抗生素在喷雾干燥后作为药物气雾剂和作为共喷雾干燥的抗生素药物：DPPC气雾剂之间存在显著差异。傅里叶变换红外光谱和共焦拉曼显微光谱被用来探测固态的组成和相互作用。喷雾干燥的MOXI在有机溶液高级喷雾干燥后变成非结晶（无定形）。这与喷雾干燥的OFLX相反，其保留部分结晶度，OFLX：DPPC粉末在某些组成下也是如此。气溶胶分散性能使用惯性冲击与批准用于人类使用的干粉吸入器装置进行。本研究表明，DPPC的使用提供了改进的MOXI作为共喷雾干燥的微粒/纳米颗粒粉末的气溶胶递送，而残留的部分结晶度影响OFLX和OFLX：DPPC吸入粉末的大部分组合物的气溶胶分散。
The aim of this study was to design and develop respirable antibiotics moxifloxacin (MOXI) hydrochloride and ofloxacin (OFLX) microparticles and nanoparticles, and multifunctional antibiotics particles with or without lung surfactant 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) for targeted dry powder inhalation delivery as a pulmonary nanomedicine. Particles were rationally designed and produced by advanced spray-drying particle engineering from an organic solution in closed mode (no water) from dilute solution. Scanning electron microscopy indicated that these particles had both optimal particle morphology and surface morphology, and the particle size distributions were suitable for pulmonary delivery. Comprehensive and systematic physicochemical characterization and in vitro aerosol dispersion performance revealed significant differences between these two fluoroquinolone antibiotics following spray drying as drug aerosols and as cospray-dried antibiotic drug: DPPC aerosols. Fourier transform infrared spectroscopy and confocal Raman microspectroscopy were employed to probe composition and interactions in the solid state. Spray-dried MOXI was rendered noncrystalline (amorphous) following organic solution advanced spray drying. This was in contrast to spray-dried OFLX, which retained partial crystallinity, as did OFLX: DPPC powders at certain compositions. Aerosol dispersion performance was conducted using inertial impaction with a dry powder inhaler device approved for human use. The present study demonstrates that the use of DPPC offers improved aerosol delivery of MOXI as cospray-dried microparticulate/nanoparticulate powders, whereas residual partial crystallinity influenced aerosol dispersion of OFLX and most of the compositions of OFLX: DPPC inhalation powders.