Department Scienze della Vita e dell'Ambiente, Sezione Scienze del Farmaco, Cagliari, Italy.
J Pharm Pharmacol. 2013 Sep;65(9):1302-11. doi: 10.1111/jphp.12094. Epub 2013 Jul 5.
In this work, a new polymeric microparticle system based on gelatin covalently bound to isoniazid (ISN) and containing rifampicin (RFP) was prepared by spray-drying technique. Microparticle aptitude to nebulisation and their capability of interacting with A549, alveolar basal epithelial cells, were evaluated in vitro.
Microparticles were obtained by spray drying, and their morphology, size, zeta potential, thermotropic behaviour and nebulisation ability were evaluated.
Microparticles were positively charged with a mean size of 4.88 ± 0.3 μm. Microspheres were able to incorporate both RFP and ISN: encapsulation efficiency was 51 ± 6% and 22 ± 1%, respectively. X-ray diffraction study showed a new extensive and flattened diffraction peak providing evidence that the drugs were dispersed into the microparticles. Differential scanning calorimetry analysis confirmed effective interactions between gelatin and drug molecules by the presence of new transition peaks. Fifty-nine per cent of used microparticles were aerosolised. In-vitro toxicity studies on A549 alveolar basal epithelial cells showed that microparticles decreased cytotoxicity in comparison with the RFP solution. Laser scanning confocal microscopy observation confirmed that fluorescent probes delivered by microparticles are efficiently internalised in A549 cells.
Overall, microparticles based on gelatin covalently bound to ISN and containing RFP showed a promising behaviour for pulmonary drug delivery.
本研究采用喷雾干燥技术，制备了一种新型的基于共价结合异烟肼（ISN）的明胶聚合物微球系统，并载有利福平（RFP）。评估了微球的雾化适性及其与肺泡基底上皮细胞（A549）相互作用的能力。
通过喷雾干燥获得微球，并对其形态、粒径、Zeta 电位、热行为和雾化能力进行了评估。
微球带正电荷，平均粒径为 4.88±0.3μm。微球能够同时包封 RFP 和 ISN：包封效率分别为 51±6%和 22±1%。X 射线衍射研究表明，存在新的广泛且平坦的衍射峰，证明药物已分散在微球中。差示扫描量热法分析证实了明胶与药物分子之间存在新的转变峰，从而实现了有效相互作用。59%的使用微球被雾化。A549 肺泡基底上皮细胞的体外毒性研究表明，与 RFP 溶液相比，微球降低了细胞毒性。激光扫描共聚焦显微镜观察证实，荧光探针通过微球被有效地内化到 A549 细胞中。
总的来说，基于共价结合异烟肼（ISN）的明胶微球并载有利福平（RFP）显示出了用于肺部药物传递的有前景的行为。
