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Joscelyn C. Mejias
BME Ph.D. Proposal Presentation
Date: Monday, April 24th 2017
Time: 2:30 PM
Location: EBB CHOA seminar room
Advisor:
Dr. Krishnendu Roy
Thesis Committee:
Dr. Andres Garcia
Dr. Manu Platt
Dr. Ravi Kane
Dr. Rabin Tirouvanziam
Title: Nano-in-Micro Multi-Stage Particles for Pulmonary Drug Delivery
Abstract:
Pulmonary drug delivery is a non-invasive method for targeted delivery of therapeutics for the treatment of respiratory diseases such as asthma, lung cancer, or cystic fibrosis. Although the lung appears to be an “easy” target for site-specific gene therapy, there are several physiologic barriers hindering its effectiveness. For particle deposition in respiratory airways, the aerodynamic diameter of particles should fall between 0.5-5 µm, however, alveolar macrophages rapidly clear particles within this geometric range. Additionally, nano-sized (< 200 nm) particles are required for efficient transport through the pulmonary mucosa and to facilitate efficient endocytosis for intracellularly targeting small molecules or biologics such as siRNA. These design parameters suggest a two-stage system is necessary for efficient therapeutic delivery; a microparticle for aerodynamic properties and a nanoparticle for drug delivery.
A nanoparticle-inside-microgel multi-stage formulation could provide efficient, intracellular, delivery of nanoparticles to target cells of interest. The microgel carriers are designed for (a) protease-triggered release of drug loaded nanoparticles, (b) avoiding rapid clearance by alveolar macrophages, and (c) appropriate aerodynamic properties, while the nanoparticles are designed to (a) carry small hydrophobic molecules and (b) bypass mucosa. The overall objective is to test this by investigating (i) how the microgels and nanoparticles interact with the phagocytic immune cells in vivo and (ii) how we can study these interactions in an in vitro setting.
