Advisor(s)

Mansoor M. Amiji

Contributor(s)

Robert Campbell, Toshiihisa Kawai, Nikolaos S. Soukos

Date of Award

2009

Date Accepted

7-2009

Degree Grantor

Northeastern University

Degree Level

M.S.

Degree Name

Master of Science

Department or Academic Unit

Bouvé College of Health Sciences. Department of Pharmaceutical Sciences.

Keywords

Pharmaceutical science, Methylene blue, Monoclonal antibody, Nanoparticles, Periodontitis, Photodynamic therapy

Subject Categories

Pharmaceutical technology

Disciplines

Pharmacy and Pharmaceutical Sciences

Abstract

Periodontitis is a chronic inflammatory disease of the periodontal tissues, which can lead to tooth loss and significant sub-gingival tissue deformities. The inflammatory process is initiated by chronic infection resulting from the presence of multi-species bacterial biofilms (dental plaques). Mechanical removal of the periodontal biofilms with or without antimicrobial agents is the current method of treatment. Antiseptics and antibiotics are also used. However, development of resistance in the target organisms is a problem associated with the use of such agents. On the other hand, Porphyromonas gingivalis is a microorganism present in dental plaque and a key player in the development of periodontitis. Selective targeting of P. gingivalis in dental plaque may lead to the development of a strategy for prevention of periodontal diseases. In the present study, we explored a) the in vitro effects of poly(lactic-co-glycolic acid) (PLGA) nanoparticles loaded with the photosensitizer methylene blue (MB) and light against Enterococcus faecalis, and b) the preparation of a conjugate between a monoclonal antibody PF18 against Porphyromonas gingivalis and MB-loaded polymeric nanoparticles for selective photosensitization of the microbe. MB-encapsulated nanoparticles of poly(lactic-co-glycolic acid) (PLGA) with negative and positive surface charge were prepared and characterized. The uptake and distribution of cationic and anionic nanoparticles in E. faecalis was investigated by transmission electron microscopy (TEM) after incubation with PLGA complexed with colloidal gold particles for 5 min. A large fraction of nanoparticles were found to be concentrated onto the cell walls of microorganisms. The synergism of light and cationic MB-loaded nanoparticles led to approximately >1 log10 reduction of colony-forming units in planktonic phase. On the other hand, the selectivity of an PF18-modified gold nanoparticle conjugate was demonstrated by TEM using P. gingivalis and E. faecalis (negative control). Our results indicate that a) PLGA nanoparticles encapsulated with photoactive drugs may be an effective adjunct in antimicrobial periodontal treatment, and b) a targeting approach may be possible for selective suppression of key pathogenic bacteria in dental plaque.

Document Type

Master's Thesis

Rights Holder

Niraj B. Patel


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