Microtek — Department of Health and Human Services SBIR Phase I: 100

Description

Project SummaryAbstractThe rate of FDA approval for respiratory drugs is onlymuch lower than drugs developed for other key therapeutic areasThe lower success rate for respiratory drugs can be attributed to the lack of innovation for developing inhaled therapeuticsespecially tools needed for early drug development phasesThe early assessment of a drug s metabolismpharmacokineticsand toxicologyDMPK toxare extremely criticalPreclinical animal studies reduce the time and costs expended with the development of new drugsthus increasing the overall success of bringing new therapies to marketHoweverfor animal models of lung diseasescurrent methods for airway dosing have major limitations that greatly affect the data qualityreliability and feasibility of DMPK tox studiesTo address these limitationsour proposed project will develop a new tool for use during the preclinical stages of drug development of inhaled therapeuticsWe will design and assemble a working prototype of a miniaturized intratracheal device that will produce aerosolized drug particles andltm in sizewhich is the optimum particle size to allow even drug distribution to the distal lungsWe will then optimize the surgical procedure for implantation of the intratracheal device in the trachea of the rat modelquantify particle deposition in the lung in single and multiple dose studiesand evaluate biocompatibility of the deviceImplantable catheters are commonly used for DMPK tox testing of oral and intravenous drugsbut a technology for an implantable system for inhaled dosing is not yet availableUpon completion of Phase Iwe will have a working prototype and surgical implantation methods for an intratracheal device that demonstrates efficient particle distribution in the lungs when administered via airway using single or multiple dosing strategiesThis will provide the foundation for Phase II studiesin which we will evaluate costsconduct comparative DMPK tox studies with existing inhalation dosing methodsand demonstrate utility in disease models in order to define specific viable market sectorsThe integration of a new tool for preclinical development of respiratory drugs will greatly improve the early stage drug development process for respiratory drugs and help advance therapeutics towards FDA approval Project NarrativeRespiratory disease is a global pandemicaffecting overbillion people worldwideWith the rising prevalence of pulmonary disorderssuch as asthma and chronic obstructive pulmonary diseasethere is an increasing need for new medicationsHoweverthe rate of market approval for respiratory drugs is onlycompared to other diseasessuch as cancer and cardiovascular diseaseThe lower success rate for respiratory drugs can be attributed to the lack of innovation for developing inhaled therapeuticsespecially tools needed for the early drug development phasesCurrentlyin vivo inhalation dosing studies remain difficulttime consumingexpensiveand inaccurateresulting in poor quality dataTo address these challengesour proposed project will develop a new tool for use during the preclinicalearly stages of development of inhaled therapeuticsThe early in vivo assessment of a drug s metabolismpharmacokineticsand toxicologyDMPK toxare extremely criticalThese studies reduce the time and costs expended with the development of new drugsthus increasing the overall success of bringing new drugs to marketSurgical implantation of catheters in rodents for dosing and sampling are widely used methods for DMPK tox studieswhich range from small scaleearly stage development in academic research settingto large scalepharmaceutical industry and CRO settingaccommodating single or multiple dosing strategiesHoweverthese methods are limited to dosing and sampling in veinsarteries and GI tract onlywhich have helped to advance the development of oral and intravenous drugsThe development of an intratracheal device for animal models would fill in this technological gapenabling the utility of improved inhaled dosing strategiesWe anticipate that an implantable intratracheal device would increase the accuracy of respiratory drug studies by improving drug distribution to the distal lung and reduction of stress in freely moving animalsIn additionthe intratracheal device will provide cost savings by reducing the loss of drugreduce excessive use of animalsand importantlyprovide reliable data for go no go decisions early in preclinical drug development