Inflammation of the dental pulp, or pulpitis, is a common, painful, and costly global public health problem that affects quality of life of patients. n most cases, pulpitis is a consequence of moderate or advanced dental caries (tooth decay), the most common chronic disease in the world. Pulpitis can also result from repeated thermal insults to a sensitive tooth, tooth attrition, trauma, microleakage of dental restorations, and periodontitis (inflammation of tissues supporting the teeth). Pulpitis is characterized by sharp shooting pain evoked by thermal stimuli (reversible pulpitis) or debilitating, dull, throbbing pain that occurs spontaneously or can be evoked by mechanical or thermal stimuli and lingers after cessation of the stimulus, necessitating emergency care (irreversible pulpitis). The quality and severity of the pain correlates with the extent of irritation from bacteria and other etiologies. Diagnosis can be complicated because the pain can be referred to other orofacial structures, or to adjacent teeth. We recently invented a new technique to deliver therapeutic agents to the pulp without affecting the integrity of the pulp chamber. To do so, we take advantage of naturally occurring dentinal tubules (~0.3 - 2 ?m diameter channels in dentin), and use magnetic forces to direct therapeutic magnetic particles into the tooth pulp. Preliminary experiments demonstrated efficient delivery of 100-500 nm starch-coated particles to the pulp chamber of extracted human teeth in approximately 30 minutes, using magnet arrays of our design. In this application, we seek funds to allow us to develop this innovative technique and to test its effect on pulpal tissues and tissues surrounding the teeth.
We aim :
Aim 1. To test the magneto-dynamics and pharmacokinetics of biocompatible nanoparticles guided to the pulp through dentinal tubules. We will use an in vitro preparation of freshly extracted human teeth and investigate: (1) The optimum particle size for delivery into the pulp;(2) The effect of polysaccharide coating (starch vs. chitosan) on the delivery of particles to the pulp;and (3) The amount of therapeutic medication (prednisolone or ofloxacin) that can be delivered to the pulp and the rate of sustained release of these therapeutic agents after magnetic force application is stopped. Nanoparticle concentrations will be determined using inductively coupled plasma atomic emission spectroscopy (ICP-AES), and drug levels will be quantified using high performance liquid chromatography coupled with mass spectrometry.
Aim 2. To quantify delivery of drug-conjugated nanoparticles to the pulp in vivo, and to evaluate the effects of these nanoparticles on pulpal tissues under normal and pathologic conditions. We will prepare cavities of various depths in the molar teeth of rats. We will apply nanoparticles coated with polysaccharides or conjugated to prednisolone, or ofloxacin (particle size will be based on results from Aim 1) and: (1) Assess changes in pulpal biology and surrounding dental tissues after the application of polysaccharide-coated nanoparticles to experimentally prepared cavities in rat molars;and (2) Test the effect of drug-conjugated nanoparticles (prednisolone, and ofloxacin) on directly or indirectly injured pulp. We will use histological examination to test for changes in pulpal biology, inflammatory cell infiltration in the pulp and tissues surrounding the tooth, thickness of periodontal ligament (tissues surrounding the tooth). We will also use ICP-AES to determine nanoparticle concentration within the teeth.

Public Health Relevance

Inflammation of the dental pulp, or pulpitis, is a common, painful, global public health problem that affects quality of life of patients. In most instances, pulpitis is a consequence of repeated insults from thermal stimuli and moderate or advanced tooth decay, the most common chronic disease in the world. Available strategies for the treatment of pulpitis are aggressive, costly, painful and outdated. They are focused at excising the affected hard tissues (cavity preparation) and the placement of a filling or in advanced cases, the radical amputation of the tooth pulp-the highly vascularized, highly innervated inner layer of the tooth. In this application, we describe an innovative technique to deliver medications locally to reduce tooth sensitivity and treat pulpitis. We exploit naturally occurring tubules withn the tooth, in the dentin layer, to magnetically control and deliver biocompatible nanoparticles carrying medications to the tooth pulp. This is a simple, conservative, and cost effective technique that may cause a paradigm shift in how dentists treat pulpal disease and may prove effective for other dental conditions that affect the teeth such as hypersensitivity and abscesses.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21DE024227-01
Application #
8676982
Study Section
Oral, Dental and Craniofacial Sciences Study Section (ODCS)
Program Officer
Lumelsky, Nadya L
Project Start
2014-05-06
Project End
2016-04-30
Budget Start
2014-05-06
Budget End
2015-04-30
Support Year
1
Fiscal Year
2014
Total Cost
$229,125
Indirect Cost
$40,125
Name
University of Maryland Baltimore
Department
Dentistry
Type
Schools of Dentistry
DUNS #
188435911
City
Baltimore
State
MD
Country
United States
Zip Code
21201