Faculty Collaboration Database

Novel molecules for intra-oral delivery of antimicrobials to prevent and treat oral infectious diseases. Biochem J 2008 Jan 15;409(2):601-9

Date

10/09/2007

Pubmed ID

17919120

DOI

10.1042/BJ20070810

Scopus ID

2-s2.0-38749094109 (requires institutional sign-in at Scopus site)   6 Citations

Abstract

New molecules were designed for efficient intra-oral delivery of antimicrobials to prevent and treat oral infection. The salivary statherin fragment, which has high affinity for the tooth enamel, was used as a carrier peptide. This was linked through the side chain of the N-terminal residue to the C-terminus of a defensin-like 12-residue peptide to generate two bifunctional hybrid molecules, one with an ester linkage and the other with an anhydride bond between the carrier and the antimicrobial components. They were examined for their affinity to a HAP (hydroxyapatite) surface. The extent of the antimicrobial release in human whole saliva was determined using 13C-NMR spectroscopy. The candidacidal activity of the molecules was determined as a function of the antimicrobial release from the carrier peptide in human saliva. The hybrid-adsorbed HAP surface was examined against Candida albicans and Aggregatibacter actinomycetemcomitans using the fluorescence technique. The bifunctional molecules were tested on human erythrocytes, GECs (gingival epithelial cells) and GFCs (gingival fibroblast cells) for cytotoxicity. They were found to possess high affinity for the HAP mineral. In human whole saliva, a sustained antimicrobial release over a period of more than 40-60 h, and candidacidal activity consistent with the extent of hybrid dissociation were observed. Moreover, the bifunctional peptide-bound HAP surface was found to exhibit antimicrobial activity when suspended in clarified human saliva. The hybrid peptides did not show any toxic influence on human erythrocytes, GECs and GFCs. These novel hybrids could be safely used to deliver therapeutic agents intra-orally for the treatment and prevention of oral infectious diseases.

Author List

Raj PA, Rajkumar L, Dentino AR

Author

Andrew Dentino BS,DDS,PhD Professor & Program Director of Periodontics in the Surgical Sciences department at Marquette University

MESH terms used to index this publication - Major topics in bold

Administration, Oral
Amino Acid Sequence
Anti-Infective Agents
Candida albicans
Circular Dichroism
Defensins
Drug Carriers
Gingival Diseases
Humans
Infection Control
Kinetics
Molecular Sequence Data
Pasteurellaceae
Peptides
Periodontal Diseases
Saliva
Salivary Proteins and Peptides