دورية أكاديمية

Spray-freeze-dried inhalable composite microparticles containing nanoparticles of combinational drugs for potential treatment of lung infections caused by Pseudomonas aeruginosa.

التفاصيل البيبلوغرافية
العنوان: Spray-freeze-dried inhalable composite microparticles containing nanoparticles of combinational drugs for potential treatment of lung infections caused by Pseudomonas aeruginosa.
المؤلفون: Yu, Shihui1,2 (AUTHOR), Pu, Xiaohui1,2,3 (AUTHOR) pgh425@163.com, Ahmed, Maizbha Uddin2 (AUTHOR), Yu, Heidi H.4 (AUTHOR), Mutukuri, Tarun Tejasvi2 (AUTHOR), Li, Jian4 (AUTHOR), Zhou, Qi Tony1,2 (AUTHOR) tonyzhou@purdue.edu
المصدر: International Journal of Pharmaceutics. Dec2021, Vol. 610, pN.PAG-N.PAG. 1p.
مصطلحات موضوعية: *PSEUDOMONAS aeruginosa infections, *LUNG infections, *CYSTIC fibrosis, *MULTIDRUG resistance, *PARTICULATE matter, *COLISTIN, *PSEUDOMONAS aeruginosa
مستخلص: [Display omitted] The multi-drug resistance of Pseudomonas aeruginosa is an overwhelming cause of terminal and persistent lung infections in cystic fibrosis (CF) patients. Antimicrobial synergy has been shown for colistin and ivacaftor, and our study designed a relatively high drug-loading dry powder inhaler formulation containing nanoparticles of ivacaftor and colistin. The ivacaftor-colistin nanosuspensions (Iva-Col-NPs) were prepared by the anti-solvent method with different stabilizers. Based on the aggregation data, the formulation 7 (F7) with DSPG-PEG-OMe as the stabilizer was selected for further studies. The F7 consisted of ivacaftor, colistin and DSPG-PEG-OMe with a mass ratio of 1:1:1. The F7 powder formulation was developed using the ultrasonic spray-freeze-drying method and exhibited a rough surface with relatively high fine particle fraction values of 61.4 ± 3.4% for ivacaftor and 63.3 ± 3.3% for colistin, as well as superior emitted dose of 97.8 ± 0.3% for ivacaftor and 97.6 ± 0.5% for colistin. The F7 showed very significant dissolution improvement for poorly water soluble ivacaftor than the physical mixture. Incorporating two drugs in a single microparticle with synchronized dissolution and superior aerosol performance will maximize the synergy and bioactivity of those two drugs. Minimal cytotoxicity in Calu-3 human lung epithelial cells and enhanced antimicrobial activity against colistin-resistant P. aeruginosa suggested that our formulation has potential to improve the treatment of CF patients with lung infections. [ABSTRACT FROM AUTHOR]
قاعدة البيانات: Academic Search Index
الوصف
تدمد:03785173
DOI:10.1016/j.ijpharm.2021.121160