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Description

Title: 1639 - Minocycline Grafted Curcumin-PLGA Nanomedicine for Local Control of Periodontal Infections

Authors:

Hsin-Ju Chang, Kaohsiung Veterans General Hospital
Pei-Wen Wang, Institute of Oral Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
Jian-Long Su, Institute of Oral Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
Dar-Bin Shieh (Presenter)
Institute of Oral Medicine, College of Medicine, National Cheng Kung University

Abstract:

Objectives: Periodontitis is a chronic inflammatory disease co-contributed by pathogenic flora and the host inflammatory responses. Dental biofilms may trigger host’s defense system to produce cytokines and enzymes that subsequently aggravate local inflammation and destruct periodontal tissues. Thus effective disease control may require breaking the vicious cycle by long-term synergistic modulation of anti-bacterial and inflammation in the therapeutic design. Minocycline is used to help treat periodontal diseases and shows good anti-bacterial efficacy over a wide spectrum of infectious pathogens. However, most current local periodontal medication only addressed antimicrobial aspect and achieved relatively short local effects. The objective of this study is to formulate localized combination therapy that integrated anti-microbial and anti-inflammation with potential sustained release kinetics.

Methods: The curcumin-PLGA nanoparticles were synthesized first via double emulsion method to encapsulate curcumin in the particle core. Minocycline was then grafted onto the curcumin-PLGA particles by covalent cross-link using EDC/NHS. The anti-bacterial efficacy was determined by MIC (minimum inhibitory concentration) and MBC (minimum bactericidal concentration) test while the biocompatibilities to human gingival fibroblasts (hGF) and human normal oral keratinocytes (hNOK) were measured by MTT assay. The inflammation genes expressions affected by the nanoparticles were evaluated by RT-QPCR.

Results: The results showed that minocycline grafted curcumin-PLGA nanoparticles presented excellent anti-bacterial efficacy to S. aureus, E. coli, A. actinomycetemcomitans and P. gingivalis in both MIC & MBC tests at nanoparticles regimen containing 0.1μg /mL minocycline. The MTT assay showed good biocompatibility of the particles to hGF and hNOK at the therapeutic dose range. Minocycline grafted curcumin-PLGA nanoparticles significantly attenuated nitric oxide production, RAW 264.7 differentiation and pro-inflammatory mediators (TNF-α and IL-1β) signaling stimulated by lipopolysaccharide (LPS).

Conclusions: These results suggest that minocycline grafted curcumin-PLGA nanoparticles may provide synergistic combination of anti-bacterial and local inflammatory modulation advantages for future applications in periodontitis infection control.

This abstract is based on research that was funded entirely or partially by an outside source:
MOST 106-2627-M-006 -001 - and 104-2314-B-006 -063 -MY3

Disclosure Statement:
The submitter must disclose the names of the organizations with which any author have a relationship, the nature of the relationship, and the clinical or research area involved. The following is submitted: NONE

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