University of Kentucky College of Pharmacy, Department of Pharmaceutical Sciences - Drug Development Division, Lexington, KY, USA ; University of Washington-Seattle, College of Pharmacy, Department of Pharmaceutics, Seattle, WA, USA.
Int J Nanomedicine. 2013;8:3489-505. doi: 10.2147/IJN.S48631. Epub 2013 Sep 17.
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.
本研究旨在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）微球和纳米颗粒，以及具有或不具有肺表面活性剂 1,2-二棕榈酰基-sn-甘油-3-磷酸胆碱（DPPC）的多功能抗生素颗粒，用于靶向干粉吸入递送来作为一种肺部纳米医学。这些颗粒是通过先进的喷雾干燥颗粒工程从有机溶液中在封闭模式（无水）下从稀溶液中合理设计和生产的。扫描电子显微镜表明，这些颗粒具有最佳的颗粒形态和表面形态，且粒径分布适合肺部给药。综合系统的物理化学特性和体外气溶胶分散性能揭示了喷雾干燥作为药物气溶胶和共喷雾干燥抗生素药物：DPPC 气溶胶后，两种氟喹诺酮抗生素之间存在显著差异。傅里叶变换红外光谱和共焦拉曼微光谱用于探测固态中的组成和相互作用。喷雾干燥的 MOXI 在经过有机溶液先进喷雾干燥后呈现无定形（非晶态）。这与喷雾干燥的 OFLX 形成对比，喷雾干燥的 OFLX 保留了部分结晶性，而某些组成的 OFLX:DPPC 粉末也是如此。使用经人体使用批准的干粉吸入装置进行惯性撞击来进行气溶胶分散性能测试。本研究表明，使用 DPPC 可改善共喷雾干燥的 MOXI 作为微粒/纳米颗粒粉末的气溶胶递药，而残留的部分结晶性影响了 OFLX 和大多数 OFLX:DPPC 吸入粉末的气溶胶分散。
