10th International Aerosol Conference September 2 - September 7, 2018 America's Center Convention Complex St. Louis, Missouri, USA
Abstract View
Designed Micro-particles for Targeted Delivery of Anti-Tubercular Drugs
CHETHANI ATHUKORALA, Hema Priyamvada, Shantanu Sur, Suresh Dhaniyala, Clarkson University
Abstract Number: 1092 Working Group: Aerosols in Medicine
Abstract Treatment of pulmonary tuberculosis remains to be a major challenge, primarily due to the intracellular localization of tubercle bacilli inside macrophages and the ability of the bacteria to form a biofilm, both of which decreases the response to antitubercular drugs. Aerosolized delivery of antitubercular drugs has recently gained interest from its potential to effectively deliver the drugs into the affected lung regions without eliciting systemic side effects. We are working on the design of a core-shell microparticle formulation for antitubercular therapy deliverable via inhalational route: the biopolymer alginate core in these particles will allow a sustained release of DNAse to degrade DNA filaments in the biofilm; the shell consisted of self-assembled peptide nanofibers will enable the delivery of antitubercular drugs and macrophage targeting. A tetrapeptide tuftsin epitope will be presented on these nanofibers to promote macrophage targeting and particle internalization, while anti-tubercular drug isoniazid conjugated to the peptide through hydrazine linkage will allow the release of drug at the target site. The details of our approach using nebulization and electrospray techniques to optimally generate these therapeutic particles in the targeted size range of 1 – 3 µm will be presented. We are currently investigating the release of DNAse from these microparticles and their interaction with macrophage cell line. Our strategy of combining in a single microparticle the delivery of antitubercular drugs, macrophage targeting, and biofilm degradation capability could allow for the development of an efficient therapy for pulmonary tuberculosis.
Keywords: Core-shell microparticles, aerosol therapy, pulmonary drug delivery, tuberculosis therapy