Bioresorbable Nanoparticles for Visual Detection of Early-Stage Dental Caries

PROJECT SUMMARY ABSTRACT This project responds to the need identified by NIDCR to develop improved methods to detect and predict progression of dental cariestooth decayto improve human healthWorldwidecaries is the most common chronic disease affecting almost everyoneDental disease is major cause of economic and social loss and leads to complications including paintooth loss and even deathGenerally inactive lesions require no treatment while active lesions doEarly active lesions permit conservative treatmentwhereas cavitated lesions require more costly and invasive restorationSince the earlyscaries diagnosis has been performed visually and using a dental explorerbut early cavities are missed and the explorer can cause cavitationAlternativelyX Rays identify more fully developed cavities but are unable to identify early forming lesionsNewer methods for caries diagnosis show little benefit and incur greater cost to dentist and patientCurrent methods diagnose a surfacedefectin the enamel but cannot distinguish between active and inactive carious lesionsa critical need in modern dentistryOur goal is to develop a new clinically valid test to diagnose early and active carious lesions that also enables effective monitoring of conservative treatmentWe have invented a nanoparticle technology which specifically targets active carious lesionsThe nanoparticles are made from food grade corn starchWe have functionalized them so they specifically target the subsurface of carious lesionsThey are tagged with a safe fluorescent dye so the caries will illuminate and be easily seen using a standard dental curing lampThis would allow dentists to quickly differentiate whether a carious lesion is active or inactive and to monitor treatment resultsThe product envisioned is a mouth rinse containing a low concentration of the nanoparticles in waterenabling visual detection of early active carious lesions otherwise invisible on the tooth surfacebecause the extremely small nanoparticles can penetrate through surface microchannels into the early active sub surface lesionThe starch based nature of the nanoparticles facilitates rapid degradation by amylase enzyme present in human salivaso teeth will no longer fluoresce upon leaving the dentist s officeWith earlier detection of caries and treatment of the disease before cavitation occursinvasive treatments will be preventedresulting in the enablement of Minimally Invasive Dentistry and improved oral healthOur preliminary research has demonstrated the potential of this technologyOur hypothesis is the functionalities on the nanoparticles can be optimized to provide a viable product with sufficient targeting and fluorescence contrast to be macroscopically visible by the dental professional on various tooth surfaces when using a standard dental curing light available in a dental practiceSuccessful completion of the Specific Aims will establish feasibility of a viable nanoparticle composition and diagnostic proof of conceptwhich are essential milestones towards further clinical validationPhase II will involve in vivo biocompatibility studiesin vitro sensitivity and specificity evaluationcaries activity assessmentclinical validation and cationic fluorescent starch nanoparticle manufacturing Randamp D for production according to FDA cGMP QSR requirements PUBLIC HEALTH RELEVANCE STATEMENT In this SBIRGreenMark Biomedical Incwill develop a diagnostic test which will be used by dental professionals as part of the routine dental exam to better detect and predict progression of dental cariesa need identified by NIDCRThe product will be a mouth rinse containing small fluorescent particles made from corn starchwhich are targeted into active carious lesions and which illuminate when using a standard dental curing lamp found in every dental practiceIt will result in improved long term oral health outcomes for patients through greater conservative treatment and less overtreatment of dental caries