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Local delivery of minocycline-loaded PEG-PLA nanoparticles for the enhanced treatment of periodontitis in dogs

Authors Yao W, Xu P, Pang Z, Zhao J, Chai Z, Li X, Li H, Jiang M, Cheng H, Zhang B, Cheng N, Pang Z

Received 10 May 2014

Accepted for publication 21 June 2014

Published 18 August 2014 Volume 2014:9(1) Pages 3963—3970


Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 4

Wenxin Yao,1 Peicheng Xu,1 Zhiqing Pang,2,3 Jingjing Zhao,2,3 Zhilan Chai,2,3 Xiaoxia Li,4 Huan Li,2,3 Menglin Jiang,2,3 Hongbo Cheng,2,3 Bo Zhang,2,3 Nengneng Cheng4

1Shanghai Xuhui District Dental Center, 2Key Laboratory of Smart Drug Delivery, Ministry of Education, 3Department of Pharmaceutics, School of Pharmacy, Fudan University, 4Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai, People’s Republic of China

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.

Keywords: minocycline, nanoparticles, periodontitis, local delivery

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