Alginate lyase immobilized chitosan nanoparticles of ciprofloxacin for the improved antimicrobial activity against the biofilm associated mucoid P. aeruginosa infection in cystic fibrosis
Alginate lyase immobilized chitosan nanoparticles of ciprofloxacin for the improved antimicrobial activity against the biofilm associated mucoid P. aeruginosa infection in cystic fibrosis
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DOI：
10.1016/j.ijpharm.2019.03.051
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发表时间：
2019-03
影响因子：
5.8
通讯作者：
K. Patel;M. Tripathi;N. Pandey;A. Agrawal;Shilpkala Gade;M. Anjum;R. Tilak;Sanjay Singh
中科院分区：
文献类型：
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作者：
K. Patel;M. Tripathi;N. Pandey;A. Agrawal;Shilpkala Gade;M. Anjum;R. Tilak;Sanjay Singh
粘液样铜绿假单胞菌在被称为生物膜的自我分泌的细胞外基质（主要是海藻酸盐）中密集定植，是囊性纤维化患者抗菌治疗失败的主要原因。藻酸盐是黏液idp生物膜的关键成分。铜绿菌负责生物膜的表面粘附和稳定。为解决这一问题，研制了海藻酸解酶功能化壳聚糖纳米粒环丙沙星，对p的有效治疗。囊性纤维化患者的铜绿杆菌感染。开发的纳米颗粒具有理想的质量属性，并表现出根据Higuchi释放动力学的持续释放。FTIR和粉末x射线衍射分析证实了与壳聚糖的药物相容性，并证实了药物在纳米颗粒基质内的包埋。乳糖吸附的NPs表现出良好的空气动力学性能。纳米颗粒在浮游细菌悬浮液中表现出延长MIC和显著减少生物膜聚集和形成的作用。纳米颗粒对磷生物膜的抑制作用明显增强。通过共聚焦显微镜观察，铜绿菌的生物量、厚度和密度均有所降低。此外，制备的纳米颗粒具有血液相容性，在体外和体内对雄性Wistar大鼠的肺没有任何毒性。现有的数据表明，提出的策略是有效治疗囊性纤维化感染的更好选择。
Dense colonization of mucoidPseudomonas aeruginosawithin the self-secreted extracellular matrix (mainly alginate), called biofilm, is a principal reason for the failure of antimicrobial therapy in cystic fibrotic patients. Alginate is a key component in the biofilm of mucoidP. aeruginosaand responsible for surface adhesion and stabilization of biofilm. To overcome this problem, alginate lyase functionalized chitosan nanoparticles of ciprofloxacin were developed for the effective treatment ofP. aeruginosainfection in cystic fibrosis patients. The developed nanoparticles were found to have desired quality attributes and demonstrated sustained release following the Higuchi release kinetics. Drug compatibility with the chitosan was confirmed by FTIR while powder X-ray diffraction analysis confirmed the entrapment of drug within the nanoparticle matrix. Lactose adsorbed NPs showed promising aerodynamic property. Nanoparticles showed prolonged MIC and significant reduction in biofilm aggregation and formation in planktonic bacterial suspension. Nanoparticles exhibited significantly higher inhibitory effect against biofilm ofP. aeruginosaand reduced the biomass, thickness and density confirmed by confocal microscopy. Furthermore, developed nanoparticles were haemocompatible and did not exhibit any toxicityin vitroMTT assay and in vivo on lungs male Wistar rats. The data in hand collectively suggest the proposed strategy a better alternative for the effective treatment of cystic fibrosis infections.