title: Polymer assisted entrapment of netilmicin in PLGA nanoparticles for sustained antibacterial activity.
abstract: This study was aimed to develop poly(dl-lactide-co-glycolide) (PLGA) nanoparticle of highly water soluble antibiotic drug, netilmicin sulfate (NS) with improved entrapment efficiency (EE) and antibacterial activity. Dextran sulfate was introduced as helper polymer to form electrostatic complex with NS. Nanoparticles were prepared by double emulsification method and optimized using 2(5-1) fractional factorial design. EE was mainly influenced by dextran sulfate: NS charge ratio and PLGA concentration, whereas particle size (PS) was affected by all factors examined. The optimized NS-loaded-NPs had EE and PS of 93.23 ± 2.7% and 140.83 ± 2.4 nm respectively. NS-loaded-NPs effectively inhibited bacterial growth compared to free NS. Sustained release protected its inactivation and reduced the decline in its killing activity over time even in presence of bronchial cells. A MIC value of 18 μg/mL was observed for NPs on P. aeruginosa. Therefore, NPs with sustained bactericidal efficiency against P. aeruginosa may provide therapeutic benefit in chronic pulmonary infection, like cystic fibrosis.
authors.affiliation: Pharmacy Department, Faculty of Technology and Engineering, The Maharaja Sayajirao University of Baroda , Vadodara, Gujarat , India , and.
authors.forename: Atul
authors.initials: A
authors.lastname: Kolate
authors.forename: Girish
authors.initials: G
authors.lastname: Kore
authors.forename: Pierre
authors.initials: P
authors.lastname: Lesimple
authors.forename: Dipesh
authors.initials: D
authors.lastname: Baradia
authors.forename: Sushilkumar
authors.initials: S
authors.lastname: Patil
authors.forename: John W
authors.initials: JW
authors.lastname: Hanrahan
authors.forename: Ambikanandan
authors.initials: A
authors.lastname: Misra
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D002460:Cell Line; D003550:Cystic Fibrosis / Q000188:drug therapy* / Q000382:microbiology; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D053758:Nanoparticles / Q000737:chemistry*; D009428:Netilmicin / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D011100:Polyglycolic Acid / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011550:Pseudomonas aeruginosa / Q000254:growth & development*
chemical_list: D000900:Anti-Bacterial Agents; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D009428:Netilmicin
keywords: Antibiotic; PLGA; Pseudomonas aeruginosa, sustained release; antimicrobial effect; nanoparticle