title: Optimization of ciprofloxacin complex loaded PLGA nanoparticles for pulmonary treatment of cystic fibrosis infections: Design of experiments approach.
abstract: Design of Experiments (DoE) is a powerful tool for systematic evaluation of process parameters' effect on nanoparticle (NP) quality with minimum number of experiments. DoE was employed for optimization of ciprofloxacin loaded PLGA NPs for pulmonary delivery against Pseudomonas aeruginosa infections in cystic fibrosis (CF) lungs. Since the biofilm produced by bacteria was shown to be a complicated 3D barrier with heterogeneous meshes ranging from 100nm to 500nm, nanoformulations small enough to travel through those channels were assigned as target quality. Nanoprecipitation was realized utilizing MicroJet Reactor (MJR) technology based on impinging jets principle. Effect of MJR parameters flow rate, temperature and gas pressure on particle size and PDI was investigated using Box-Behnken design. The relationship between process parameters and particle quality was demonstrated by constructed fit functions (R2=0.9934 p<0.0001 and R2=0.9983 p<0.0001, for particle size and PDI, respectively). Prepared nanoformulations varied between 145.2 and 979.8nm with PDI ranging from 0.050 to 1.00 and showed encapsulation efficiencies >65%. Response surface plots provided experimental data-based understanding of MJR parameters' effect, thus NP quality. Presented work enables ciprofloxacin loaded PLGA nanoparticle preparations with pre-defined quality to fulfill the requirements of local drug delivery under CF disease conditions.
authors.affiliation: MJR PharmJet GmbH, Industriestr. 1B, 66802 Überherrn, Germany; Biopharmaceutics and Pharmaceutical Technology, Department of Pharmacy, Saarland University, 66123 Saarbrücken, Germany. Electronic address: n.guenday@mjr-pharmjet.com.
authors.forename: Nazende
authors.initials: N
authors.lastname: Günday Türeli
authors.affiliation: MJR PharmJet GmbH, Industriestr. 1B, 66802 Überherrn, Germany.
authors.forename: Akif Emre
authors.initials: AE
authors.lastname: Türeli
authors.affiliation: Biopharmaceutics and Pharmaceutical Technology, Department of Pharmacy, Saarland University, 66123 Saarbrücken, Germany.
authors.forename: Marc
authors.initials: M
authors.lastname: Schneider
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology; D018441:Biofilms / Q000187:drug effects; D002626:Chemistry, Pharmaceutical / Q000379:methods; D002939:Ciprofloxacin / Q000737:chemistry* / Q000494:pharmacology*; D003550:Cystic Fibrosis / Q000188:drug therapy*; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry*; D008168:Lung / Q000187:drug effects; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011552:Pseudomonas Infections / Q000188:drug therapy; D011550:Pseudomonas aeruginosa / Q000187:drug effects
chemical_list: D000900:Anti-Bacterial Agents; D004337:Drug Carriers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D002939:Ciprofloxacin
keywords: Antibiotic-loaded nanoparticles; Ciprofloxacin (PubChem CID: 2764); Design-of-experiments; Pluronic(®) F68 (PubChem CID: 24751); Poly(DL-lactide-co-glycolide) (PubChem SID 24866924); Process optimization; Quality-by-design; Sodium dodecyl sulfate (PubChem CID: 3423265)