Mishra Brahmeshwar, Mishra Madhusmita, Yadav Sarita Kumari
Department of Pharmaceutics, Indian Institute of Technology, (Banaras Hindu University), Varanasi-221005, India.
Department of Pharmacy, Moti Lal Nehru Medical College, Allahabad-211002, India.
Iran J Pharm Res. 2017 Winter;16(1):74-92.
Inhalation delivery of aerosolized antibacterials is preferred over conventional methods of delivery for targeting lung infection. The present study is concerned with the development and characterization of a novel, spray dried, aerosolized, chitosan polyelectrolyte complex (PEC) based microparticles containing antibacterials for the treatment of lung infections. Chitosan polyelectrolyte complex microparticles were formulated by spray drying process. Prepared spray dried chitosan PEC microparticles were studied for surface morphology, drug encapsulation efficiency, moisture content, Carr's index, solid state interaction by XRD, aerosolization behaviour and drug release. cytotoxicity studies of microparticles were carried out on H1299 alveolar cell lines. Antibacterial efficacy of microparticles was assessed on the basis of determination of pharmacokinetic parameters in bronchial alveolar lavage (BAL) of rats using PK/PD analysis. The PEC microparticles were mostly spherical and exhibited high drug encapsulation efficiency. Release profiles showed an initial burst phase followed by a secondary sustained release phase. Good aerosolization behaviour as dry powder inhaler was demonstrated by microparticles with high values of recovered dose, emitted dose, and fine particle fraction. No overt cytotoxicity of microparticles was detected against H1299 alveolar cell line. More than 8 to 9 folds higher C values were obtained in BAL fluid with microparticles as compared to intravenously administered antibacterial solution. The findings of the study suggest that chitosan polyelectrolyte complex based microparticles as dry powder inhaler can be an efficient antibacterial delivery system for sustained and effective management of lung infection.
对于肺部感染的靶向治疗,雾化抗菌药物的吸入给药优于传统给药方法。本研究关注的是一种新型的、喷雾干燥的、雾化的、基于壳聚糖聚电解质复合物(PEC)的含抗菌药物微粒的开发与表征,用于治疗肺部感染。壳聚糖聚电解质复合物微粒通过喷雾干燥工艺制备。对制备的喷雾干燥壳聚糖PEC微粒进行了表面形态、药物包封率、水分含量、卡尔指数、XRD固态相互作用、雾化行为和药物释放研究。在H1299肺泡细胞系上进行了微粒的细胞毒性研究。使用PK/PD分析,通过测定大鼠支气管肺泡灌洗(BAL)中的药代动力学参数来评估微粒的抗菌效果。PEC微粒大多呈球形,具有较高的药物包封率。释放曲线显示出初始突释阶段,随后是二次缓释阶段。具有高回收剂量、发射剂量和细颗粒分数值的微粒表现出作为干粉吸入器的良好雾化行为。未检测到微粒对H1299肺泡细胞系有明显的细胞毒性。与静脉注射抗菌溶液相比,微粒在BAL液中的C值高出8至9倍以上。该研究结果表明,基于壳聚糖聚电解质复合物的微粒作为干粉吸入器可以成为一种有效的抗菌给药系统,用于持续有效地管理肺部感染。