期刊
JOURNAL OF PHARMACY AND PHARMACOLOGY
卷 65, 期 9, 页码 1302-1311出版社
WILEY-BLACKWELL
DOI: 10.1111/jphp.12094
关键词
A549 cells; antimicobacterial drugs; microparticles; pulmonary drug delivery; toxicity studies
资金
- Fondazione Banco di Sardegna
- MIUR [2010H834LS_004]
Objectives 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. Methods Microparticles were obtained by spray drying, and their morphology, size, zeta potential, thermotropic behaviour and nebulisation ability were evaluated. Key findings Microparticles were positively charged with a mean size of 4.88 +/- 0.3m. 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. Conclusions Overall, microparticles based on gelatin covalently bound to ISN and containing RFP showed a promising behaviour for pulmonary drug delivery.
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