A novel chronopharmacological drug delivery systems based on PEG-containing nanoparticles for protein delivery
Abstract
In this work, novel chrono-pharmacological drug delivery systems based on a multilayer microcapsule were developed. The multilayer microcapsules consisted of drug containing hydrogel layers and seal coatings. The hydrogel layer was prepared from poly(ethylene-glycol)-containing nanoparticles and the seal coating was prepared from ethyl cellulose dispersions. The systems were designed such that upon contact with water, water molecule started to diffuse through the seal coat and swell the hydrogel nanoparticles. This build-up pressure from the osmotic pressure and the swelling of the nanoparticles forced the seal coat to rupture and exposed the crosslinked hydrogel nanoparticles, which dispersed and released the drug loaded inside them. The PEG-nanoparticle systems were prepared using a thermal initiated dispersion polymerization. Temperature sensitive PNIPAAm was included into the systems along with PEGDMA as the crosslinker. The nanoparticle systems were designed to have a high loading efficiency and to be able to protect highly sensitive therapeutic agents from the high temperature, high shear stress, and high air/liquid interface encountered during the Wurster bed coating process. The size of the nanoparticles changed by one order of magnitude when the temperature of the system was changed from 5°C to 35°C as measured using the photon correlation spectroscopy. The nanoparticulate systems were able to protect insulin from the simulated harsh environment encountered during the coating process. In order to elucidate the structure and performance of the multilayer microcapsules, several microscopic techniques were employed. Polarizing microscopy was employed to observe the uniformity of the layers created and also to observe the redispersion of the PEG-nanoparticles. Fluorescent microscopy was utilized to observe the release behavior of FD4 from the multilayer microcapsules. Confocal laser scanning microscopy was used to dissect the microcapsule and observe the uniformity of each layer throughout. Factors affecting the coating process, such as the feed rate of the dispersions, the flow rate of the air, and the temperature of the inlet air were investigated and optimized. These intensive studies of the multilayer microcapsules, the PEG-containing nanoparticles, and the seal coat materials showed that these systems had the potential to be applied as a chronopharmacological drug delivery system.
Degree
Ph.D.
Advisors
Peppas, Purdue University.
Subject Area
Chemical engineering|Pharmacology
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