Shanghai Xuhui District Dental Center

Shanghai, China

Shanghai Xuhui District Dental Center

Shanghai, China
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Yao W.,Shanghai Xuhui District Dental Center | Xu P.,Shanghai Xuhui District Dental Center | Pang Z.,Key Laboratory of Smart Drug Delivery | Pang Z.,Fudan University | And 14 more authors.
International Journal of Nanomedicine | Year: 2014

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. © 2014 Yao et al.


Yao W.,Shanghai Xuhui District Dental Center | Xu P.,Shanghai Xuhui District Dental Center | Zhao J.,Fudan University | Ling L.,Fudan University | And 4 more authors.
Journal of Colloid and Interface Science | Year: 2015

Long term retention of antimicrobials with effective drug concentration in gingival crevicular fluid (GCF) is of vital importance for the treatment of chronic periodontitis. In this study, a novel epithelial cell-targeting nanoparticle drug delivery system by conjugating minocycline-loaded poly(ethylene glycol)-poly(lactic acid) (PEG-PLA) nanoparticles (NP-MIN) with RGD peptide were developed and administrated locally for targeting periodontitis epithelial cells and enhancing the treatment of periodontitis in dogs. Biodegradable NP-MIN was made with an emulsion/solvent evaporation technique. RGD peptide was conjugated to the surface of nanoparticles via Maleimide group reaction with hydrosulfide in RGD peptide (RGD-NP-MIN). Transmission electron microscopy examination and dynamic light scattering results revealed that RGD-NP-MIN had a sphere shape, with a mean diameter around 106. nm. In vitro release of minocycline from RGD-NP-MIN showed that RGD modification did not change the remarkable sustained releasing characteristic of NP-MIN. To elucidate the interaction of RGD-NP and epithelial cells, RGD-NP binding, uptake and cellular internalization mechanisms by calu-3 cells were investigated. It was shown RGD modification significantly enhanced nanoparticles binding and uptake by Calu-3 cells, and RGD-NP uptake was an energy-dependent process through receptor-mediated endocytosis. Both clathrin-associated endocytosis and caveolae-dependent endocytosis pathway were involved in the RGD-NP uptake, and the intracellular transport of RGD-NP was related to lysosome and Golgi apparatus. Finally, i. n vivo pharmacokinetics of minocycline in the periodontal pockets and anti-periodontitis effects of RGD-NP-MIN on periodontitis-bearing dogs were evaluated. After local administration of RGD-NP-MIN, minocycline concentration in gingival crevicular fluid decreased slowly and maintained an effective drug concentration for a longer time than that of NP-MIN. Anti-periodontitis effects demonstrated that RGD-NP-MIN could significantly decrease symptoms of periodontitis, which was better than any other control group. These findings suggested that these epithelial cell-targeting nanoparticles offered a novel and effective local delivery system for the treatment of periodontitis. © 2015 Elsevier Inc.


Qian W.,Shanghai Xuhui District Dental Center | Xu P.,Shanghai Xuhui District Dental Center | Lu G.,CAS Shanghai Institute of Organic Chemistry | Huang X.,CAS Shanghai Institute of Organic Chemistry
Chinese Journal of Chemistry | Year: 2014

A well-defined amphiphilic graft copolymer, consisting of hydrophobic poly(tert-butyl acrylate) (PtBA) backbone and hydrophilic poly(N-vinylcaprolactam) (PNVCL) side chains, was synthesized by successive reversible addition-fragmentation chain transfer (RAFT) polymerization and atom transfer radical polymerization (ATRP). A new acrylate monomer bearing a chlorine-based initiating group, tert-butyl 2-((2-chloropropanoyloxy)methyl)acrylate, was first RAFT homopolymerized in a controlled way to give a well-defined homopolymer with a narrow molecular weight distribution (Mw/Mn=1.15). This homopolymer directly initiated ATRP of N-vinylcaprolactam (NVCL) to afford a well-defined PtBA-g-PNVCL graft copolymer (Mw/Mn=1.22) via the grafting-from strategy without polymeric functionality transformation. PAA-g-PNVCL graft copolymer was prepared by selectively hydrolyzing PtBA-g-PNVCL. Ornidazole (ONZ)-loaded polymeric micelles using PAA-g-PNVCL copolymer as carrier were prepared by physical entrapping. Drug release experiment of the nano-carrier indicated the pH-dependent drug release characteristics. © 2014 SIOC, CAS, Shanghai & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.


Qian W.,Shanghai Xuhui District Dental Center | Song X.,CAS Shanghai Institute of Organic Chemistry | Feng C.,CAS Shanghai Institute of Organic Chemistry | Xu P.,Shanghai Xuhui District Dental Center | And 3 more authors.
Polymer Chemistry | Year: 2016

A series of well-defined amphiphilic brush polymers containing hydrophilic poly(ethylene glycol) (PEG) and hydrophobic poly(lactic acid) segments was synthesized by the combination of reversible addition-fragmentation chain transfer (RAFT) polymerization, ring opening polymerization (ROP), and the grafting-from strategy. tert-Butyl 2-((4-hydroxybutanoyloxy)methyl)acrylate (tBHBMA) monomer containing a ROP initiation group (-OH) was first RAFT block copolymerized using a PEG-based chain transfer agent to form two well-defined PEG-b-PtBHBMA diblock copolymers (Mw/Mn ≤ 1.10) bearing pendant hydroxyls in every repeated unit of PtBHBMA segment. Both diblock copolymers directly initiated ROP of lactide by the pendant hydroxyls to provide well-defined poly(ethylene glycol)-b-(poly(tert-butyl acrylate)-g-poly(lactic acid)) (PEG-b-(PtBA-g-PLA)) brush polymers (Mw/Mn ≤ 1.16) without post-polymerization functionality transformation. The target well-defined poly(ethylene glycol)-b-(polyacrylic acid)-g-poly(lactic acid) (PEG-b-(PAA-g-PLA)) amphiphilic brush polymers were achieved by the selective acidolysis of hydrophobic PtBA backbone (tert-butyoxycarbonyls) into hydrophilic PAA backbone (carboxyls) using trifluoroacetic acid. PEG-b-(PAA-g-PLA) brush polymers could self-assemble into spheres with a size of ca. 70-110 nm in aqueous media as evidenced by DLS and TEM. The drug (doxorubicin) loading ability of PEG-b-(PAA-g-PLA) brush polymers was investigated preliminarily by measuring the in vitro cell (SMMC-7721 and SH-SY5Y) viabilities, which showed higher cytotoxicity compared to free DOX. © The Royal Society of Chemistry 2016.


Qian W.,Tongji University | Qian W.,Shanghai Xuhui District Dental Center | Su J.,Tongji University | Gong X.,Tongji University | And 2 more authors.
Chinese Journal of Organic Chemistry | Year: 2015

The end of linear m-PEG-OH was functionalized to provide m-PEG-CTA macro-RAFT agent. RAFT homopolymerization of tBHBMA was conducted to give PEG-b-PtBHBMA diblock copolymer, which initiated ROP of lactide directly. The obtained graft copolymer, PEG-b-(PtBA-g-PLA), was then esterified with 7-methoxycoumarin-3- carboxylic acid to afford PEG-b-(PtBA-g-PLA-COU) containing fluorescent dye molecule. PEG-b-(PAA-g-PLA-COU) amphiphilic graft copolymer was prepared by selective hydrolysis of PtBA segment. Finally, doxorubicin (DOX) was loaded into polymeric micelles aggregated by PEG-b-(PAA-g-PLA-COU). The drug loading content (DLC) and size of the obtained polymeric drug micelles containing fluorescent dye molecule was measured by UV-vis and DLS. © 2015 Chinese Chemical Society & SIOC, CAS.


Qian W.,Shanghai Xuhui District Dental Center | Xu P.,Shanghai Xuhui District Dental Center | Su J.,Tongji University | Lu G.,CAS Shanghai Institute of Organic Chemistry | Huang X.,CAS Shanghai Institute of Organic Chemistry
Chinese Journal of Organic Chemistry | Year: 2013

Two composite resin bonders were prepared via in-situ polymerization and blending method using Bis-GMA as resin matrix and nano-SiO2 as inorganic filler. Composite resin bonder A was composed of crosslinked copolymer of Bis-GMA/TEDMA and nano-SiO2, and composite resin bonder B contained crosslinked copolymer of Bis-GMA/HEMA and nano-SiO2. Both composite resins were employed as luting agent to bond fiber posts into root canals and the effects of temperature fatigue and mechanical fatigue on their shear bonding strength were studied. © 2013 Chinese Chemical Society & SIOC, CAS.

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