title: Poly(glycerol adipate-co-ω-pentadecalactone) spray-dried microparticles as sustained release carriers for pulmonary delivery.
abstract: OBJECTIVE
  The aim of this work was to optimize biodegradable polyester poly(glycerol adipate-co-ω-pentadecalactone), PGA-co-PDL, microparticles as sustained release (SR) carriers for pulmonary drug delivery.
  
  
  METHODS
  Microparticles were produced by spray drying directly from double emulsion with and without dispersibility enhancers ((L)-arginine and (L)-leucine) (0.5-1.5%w/w) using sodium fluorescein (SF) as a model hydrophilic drug.
  
  
  RESULTS
  Spray-dried microparticles without dispersibility enhancers exhibited aggregated powders leading to low fine particle fraction (%FPF) (28.79 ± 3.24), fine particle dose (FPD) (14.42 ± 1.57 μg), with a mass median aerodynamic diameter (MMAD) 2.86 ± 0.24 μm. However, (L)-leucine was significantly superior in enhancing the aerosolization performance ((L-)arginine:%FPF 27.61 ± 4.49-26.57 ± 1.85; FPD 12.40 ± 0.99-19.54 ± 0.16 μg and MMAD 2.18 ± 0.35-2.98 ± 0.25 μm, (L)-leucine:%FPF 36.90 ± 3.6-43.38 ± 5.6; FPD 18.66 ± 2.90-21.58 ± 2.46 μg and MMAD 2.55 ± 0.03-3.68 ± 0.12 μm). Incorporating (L)-leucine (1.5%w/w) reduced the burst release (24.04 ± 3.87%) of SF compared to unmodified formulations (41.87 ± 2.46%), with both undergoing a square root of time (Higuchi's pattern) dependent release. Comparing the toxicity profiles of PGA-co-PDL with (L)-leucine (1.5%w/w) (5 mg/ml) and poly(lactide-co-glycolide), (5 mg/ml) spray-dried microparticles in human bronchial epithelial 16HBE14o- cell lines, resulted in cell viability of 85.57 ± 5.44 and 60.66 ± 6.75%, respectively, after 72 h treatment.
  
  
  CONCLUSIONS
  The above data suggest that PGA-co-PDL may be a useful polymer for preparing SR microparticle carriers, together with dispersibility enhancers, for pulmonary delivery.
authors.affiliation: School of Pharmacy & Biomolecular Sciences, Liverpool John Moores University, James Parsons Building, Byrom Street, Liverpool L33AF, UK.
authors.forename: Hesham
authors.initials: H
authors.lastname: Tawfeek
authors.forename: Sayed
authors.initials: S
authors.lastname: Khidr
authors.forename: Eman
authors.initials: E
authors.lastname: Samy
authors.forename: Sayed
authors.initials: S
authors.lastname: Ahmed
authors.forename: Mark
authors.initials: M
authors.lastname: Murphy
authors.forename: Afzaal
authors.initials: A
authors.lastname: Mohammed
authors.forename: Anjum
authors.initials: A
authors.lastname: Shabir
authors.forename: Gillian
authors.initials: G
authors.lastname: Hutcheon
authors.forename: Imran
authors.initials: I
authors.lastname: Saleem
mesh_terms: D000336:Aerosols; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003692:Delayed-Action Preparations / Q000008:administration & dosage* / Q000493:pharmacokinetics; D004337:Drug Carriers / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D004339:Drug Compounding / Q000379:methods; D004847:Epithelial Cells / Q000187:drug effects; D006801:Humans; D008168:Lung / Q000378:metabolism; D008855:Microscopy, Electron, Scanning; D008863:Microspheres; D015394:Molecular Structure; D010316:Particle Size; D011091:Polyesters / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D011208:Powders; D012995:Solubility; D013499:Surface Properties; D014018:Tissue Distribution
chemical_list: D000336:Aerosols; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D011091:Polyesters; D011208:Powders; C568823:poly(glycerol adipate-co-omega-pentadecalactone)