Ciprofloxacin-loaded PLGA nanoparticles against cystic fibrosis P. aeruginosa lung infections

Eur J Pharm Biopharm. 2017 Aug:117:363-371. doi: 10.1016/j.ejpb.2017.04.032. Epub 2017 May 2.

Abstract

Current pulmonary treatments against Pseudomonas aeruginosa infections in cystic fibrosis (CF) lung suffer from deactivation of the drug and immobilization in thick and viscous biofilm/mucus blend, along with the general antibiotic resistance. Administration of nanoparticles (NPs) with high antibiotic load capable of penetrating the tight mesh of biofilm/mucus can be an advent to overcome the treatment bottlenecks. Biodegradable and biocompatible polymer nanoparticles efficiently loaded with ciprofloxacin complex offer a solution for emerging treatment strategies. NPs were prepared under controlled conditions by utilizing MicroJet Reactor (MJR) to yield a particle size of 190.4±28.6nm with 0.089 PDI. Encapsulation efficiency of the drug was 79% resulting in a loading of 14%. Release was determined to be controlled and medium-independent in PBS, PBS+0.2% Tween 80 and simulated lung fluid. Cytotoxicity assays with Calu-3 cells and CF bronchial epithelial cells (CFBE41o-) indicated that complex-loaded PLGA NPs were non-toxic at concentrations ≫ MICcipro against lab strains of the bacteria. Antibacterial activity tests revealed enhanced activity when applied as nanoparticles. NPs' colloidal stability in mucus was proven. Notably, a decrease in mucus turbidity was observed upon incubation with NPs. Herewith, ciprofloxacin complex-loaded PLGA NPs are introduced as promising pulmonary nano drug delivery systems against P.aeruginosa infections in CF lung.

Keywords: Antibiotic-loaded nanoparticles; Biofilm; Ciprofloxacin (PubChem CID: 2764); Nanomedicines; Pluronic® F68 (PubChem CID: 24751); Poly(dl-lactide-co-glycolide) (PubChem SID: 24866924); Pulmonary nanoparticulate drug delivery; Sodium dodecyl sulfate (PubChem CID: 3423265).

MeSH terms

  • Animals
  • Cell Line
  • Ciprofloxacin / administration & dosage*
  • Ciprofloxacin / metabolism
  • Cystic Fibrosis* / drug therapy
  • Cystic Fibrosis* / metabolism
  • Drug Carriers / administration & dosage
  • Drug Carriers / metabolism
  • Horses
  • Humans
  • Lactic Acid / administration & dosage*
  • Lactic Acid / metabolism
  • Mucus / drug effects
  • Mucus / metabolism
  • Mucus / microbiology
  • Nanoparticles / administration & dosage*
  • Nanoparticles / metabolism
  • Polyglycolic Acid / administration & dosage*
  • Polyglycolic Acid / metabolism
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Pseudomonas aeruginosa / drug effects*
  • Pseudomonas aeruginosa / metabolism
  • Respiratory Mucosa / drug effects
  • Respiratory Mucosa / metabolism
  • Respiratory Mucosa / microbiology
  • Respiratory Tract Infections* / drug therapy
  • Respiratory Tract Infections* / metabolism

Substances

  • Drug Carriers
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Polyglycolic Acid
  • Lactic Acid
  • Ciprofloxacin