Magnetic Delivery of Therapeutic Nanoparticles to the Dental Pulp

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DESCRIPTION (provided by applicant): 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.