title: Local delivery of minocycline-loaded PEG-PLA nanoparticles for the enhanced treatment of periodontitis in dogs.
abstract: BACKGROUND
  Rapid local drug clearance of antimicrobials is a major drawback for the treatment of chronic periodontitis. In the study reported here, minocycline-loaded poly(ethylene glycol)-poly(lactic acid) nanoparticles were prepared and administered locally for long drug retention and enhanced treatment of periodontitis in dogs.
  
  
  METHODS
  Biodegradable poly(ethylene glycol)-poly(lactic acid) was synthesized to prepare nanoparticles using an emulsion/solvent evaporation technique. The particle size and zeta potential of the minocycline-loaded nanoparticles (MIN-NPs) were determined by dynamic light scattering and the morphology of the nanoparticles was observed by transmission electron microscopy. The in vitro release of minocycline from MIN-NPs and in vivo pharmacokinetics of minocycline in gingival crevice fluid, after local administration of MIN-NPs in the periodontal pockets of beagle dogs with periodontitis, were investigated. The anti-periodontitis effects of MIN-NPs on periodontitis-bearing dogs were finally evaluated.
  
  
  RESULTS
  Transmission electron microscopy examination and dynamic light scattering results revealed that the MIN-NPs had a round shape, with a mean diameter around 100 nm. The in vitro release of minocycline from MIN-NPs showed a remarkably sustained releasing characteristic. After local administration of the MIN-NPs, minocycline concentration in gingival crevice fluid decreased slowly and retained an effective drug concentration for a longer time (12 days) than Periocline(®). Anti-periodontitis effects demonstrated that MIN-NPs could significantly decrease symptoms of periodontitis compared with Periocline and minocycline solution. These findings suggest that MIN-NPs might have great potential in the treatment of periodontitis.
authors.affiliation: Shanghai Xuhui District Dental Center, Fudan University, Shanghai, People's Republic of China.
authors.forename: Wenxin
authors.initials: W
authors.lastname: Yao
authors.affiliation: Shanghai Xuhui District Dental Center, Fudan University, Shanghai, People's Republic of China.
authors.forename: Peicheng
authors.initials: P
authors.lastname: Xu
authors.affiliation: Key Laboratory of Smart Drug Delivery, Ministry of Education, Fudan University, Shanghai, People's Republic of China ; Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai, People's Republic of China.
authors.forename: Zhiqing
authors.initials: Z
authors.lastname: Pang
authors.affiliation: Key Laboratory of Smart Drug Delivery, Ministry of Education, Fudan University, Shanghai, People's Republic of China ; Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai, People's Republic of China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Key Laboratory of Smart Drug Delivery, Ministry of Education, Fudan University, Shanghai, People's Republic of China ; Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai, People's Republic of China.
authors.forename: Zhilan
authors.initials: Z
authors.lastname: Chai
authors.affiliation: Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai, People's Republic of China.
authors.forename: Xiaoxia
authors.initials: X
authors.lastname: Li
authors.affiliation: Key Laboratory of Smart Drug Delivery, Ministry of Education, Fudan University, Shanghai, People's Republic of China ; Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai, People's Republic of China.
authors.forename: Huan
authors.initials: H
authors.lastname: Li
authors.affiliation: Key Laboratory of Smart Drug Delivery, Ministry of Education, Fudan University, Shanghai, People's Republic of China ; Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai, People's Republic of China.
authors.forename: Menglin
authors.initials: M
authors.lastname: Jiang
authors.affiliation: Key Laboratory of Smart Drug Delivery, Ministry of Education, Fudan University, Shanghai, People's Republic of China ; Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai, People's Republic of China.
authors.forename: Hongbo
authors.initials: H
authors.lastname: Cheng
authors.affiliation: Key Laboratory of Smart Drug Delivery, Ministry of Education, Fudan University, Shanghai, People's Republic of China ; Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai, People's Republic of China.
authors.forename: Bo
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai, People's Republic of China.
authors.forename: Nengneng
authors.initials: N
authors.lastname: Cheng
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000032:analysis* / Q000737:chemistry / Q000493:pharmacokinetics*; D004195:Disease Models, Animal; D004285:Dogs; D004337:Drug Carriers / Q000737:chemistry* / Q000493:pharmacokinetics / Q000627:therapeutic use; D005883:Gingival Crevicular Fluid / Q000737:chemistry / Q000187:drug effects; D007773:Lactates / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D008911:Minocycline / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D010316:Particle Size; D010512:Periodontal Index; D010518:Periodontitis / Q000188:drug therapy* / Q000378:metabolism; D011092:Polyethylene Glycols / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D011897:Random Allocation
chemical_list: D000900:Anti-Bacterial Agents; D004337:Drug Carriers; D007773:Lactates; C088513:poly(lactic acid-ethylene glycol); D011092:Polyethylene Glycols; D008911:Minocycline
keywords: local delivery; minocycline; nanoparticles; periodontitis