Formulation, characterization and pulmonary deposition of nebulized celecoxib encapsulated nanostructured lipid carriers.
Formulation, characterization and pulmonary deposition of nebulized celecoxib encapsulated nanostructured lipid carriers.
复制标题
DOI：
10.1016/j.jconrel.2010.02.006
复制
发表时间：
2010-06-01
期刊：
影响因子：
--
通讯作者：
Singh M
中科院分区：
文献类型：
--
作者：
Patlolla RR;Chougule M;Patel AR;Jackson T;Tata PN;Singh M
本研究的目的是将塞来昔布（Cxb）包封在纳米结构脂质载体（Cxb-NLC）纳米颗粒中，并评价雾化吸入Balb/c小鼠后纳米颗粒的肺部分布。使用高压均质化用Cxb、Compritol、Miglyol和牛磺胆酸钠制备Cxb-NLC纳米颗粒。Cxb-NLC纳米颗粒的物理和气溶胶特性进行了表征。用A549细胞进行体外细胞毒性研究。使用Inexpose™系统和Pari LC星星喷射雾化器测定Cxb-NLC和Cxb溶液（Cxb-Soln）制剂的肺沉积和药代动力学参数。Cxb-NLC制剂的粒径和包封率分别为217 ± 20 nm和> 90%。Cxb-NLC以受控方式释放药物，Cxb-NLC制剂的体外雾化显示FPF为75.6 ± 4.6%，MMAD为1.6 ±0.13 μm，GSD为1.2 ± 0.21。Cxb-NLC对A549细胞显示出剂量和时间依赖性的细胞毒性。Cxb-NLC的雾化显示肺组织中的AUCt/D比Cxb-Soln高4倍。Cxb-NLC的全身清除率（0.93 L/h）低于Cxb-Soln（20.03 L/h）。发现Cxb包封的NLC是稳定的，并且空气动力学性质在可吸入限度内。与溶液制剂相比，Cxb-NLC的雾化改善了Cxb的肺部生物利用度，这可能导致患者对最小给药间隔的依从性更好。
The aim of the current study was to encapsulate celecoxib (Cxb) in the Nanostructured Lipid Carrier (Cxb-NLC) nanoparticles and evaluate the lung disposition of nanoparticles following nebulization in Balb/c mice. Cxb-NLC nanoparticles were prepared with Cxb, Compritol, Miglyol and sodium taurocholate using high-pressure homogenization. Cxb-NLC nanoparticles were characterized for physical and aerosol properties. In-vitro cytotoxicity studies were performed with A549 cells. The lung deposition and pharmacokinetic parameters of Cxb-NLC and Cxb solution (Cxb-Soln) formulations were determined using Inexpose™ system and Pari LC star jet nebulizer. The particle size and entrapment efficiency of Cxb-NLC formulation were 217 ± 20 nm and > 90%, respectively. The Cxb-NLC released the drug in controlled fashion, and in vitro aersolization of Cxb-NLC formulation showed FPF of 75.6 ± 4.6 %, MMAD of 1.6 ±0.13 μm and GSD of 1.2 ± 0.21. Cxb-NLC showed dose and time dependent cytotoxicity against A549 cells. Nebulization of Cxb-NLC demonstrated 4 fold higher AUCt/D in lung tissues compared to Cxb-Soln. The systemic clearance of Cxb-NLC was slower (0.93 L/h) compared to Cxb-Soln (20.03 L/h). Cxb encapsulated NLC were found to be stable and aerodynamic properties were within the respirable limits. Aerosolization of Cxb-NLC improved the Cxb pulmonary bioavailability compared to solution formulation which will potentially lead to better patient compliance with minimal dosing intervals.
登录
查看更多内容
影响因子：
5.8
作者：
Muller, RH;Ruhl, D;Runge, SA
通讯作者：
Runge, SA
影响因子：
3.8
作者：
BYRON, PR
通讯作者：
BYRON, PR
影响因子：
5.8
作者：
Müller, RH;Radtke, M;Wissing, SA
通讯作者：
Wissing, SA
影响因子：
2.7
作者：
Cooney, D;Kazantseva, M;Hickey, AJ
通讯作者：
Hickey, AJ
影响因子：
3.8
作者：
Kasting, GB;Francis, WR;Kinnett, GO
通讯作者：
Kinnett, GO