Please use this identifier to cite or link to this item:
http://arks.princeton.edu/ark:/88435/dsp015425kd94c
Full metadata record
DC Field | Value | Language |
---|---|---|
dc.contributor.advisor | PriestleyPrud'homme, RodneyRobert DK | |
dc.contributor.author | Caggiano, Nicholas | |
dc.contributor.other | Chemical and Biological Engineering Department | |
dc.date.accessioned | 2023-07-06T20:26:09Z | - |
dc.date.available | 2023-07-06T20:26:09Z | - |
dc.date.created | 2023-01-01 | |
dc.date.issued | 2023 | |
dc.identifier.uri | http://arks.princeton.edu/ark:/88435/dsp015425kd94c | - |
dc.description.abstract | Nanoparticle encapsulation is an attractive technique for the solubility enhancement of poorly soluble oral therapeutics since the increased specific surface area of the nanoparticles promotes rapid dissolution kinetics while avoiding the need for chemical modification of the drug molecule. Additionally, for nanoparticles produced by rapid quenching or precipitation, the resulting amorphous drug core can offer thermodynamically increased solubility relative to the crystalline form. We employ Flash NanoPrecipitation (FNP), a scalable self-assembly process which uses turbulent mixing and rapid precipitation, to form polymer-stabilized core-shell nanoparticles with high core loading (~50% or higher). However, in our application of FNP to hydrophobic small molecules and peptides we show that the physical and chemical properties of therapeutics can present obstacles to nanoparticle formulation. We describe nanoparticle formulations of cannabidiol, a hydrophobic small molecule oil, using FNP. However, the low density of cannabidiol required development of a new method to characterize in vitro dissolution from cannabidiol-loaded nanoparticles. In the case of delamanid, a hydrophobic but highly crystalline small molecule, surface stabilizer attachment during self-assembly was inhibited by suspected incompatibility caused by the fluorinated and nitro-substituted drug molecule. Therefore, emulsification was used as an alternative route to prepare delamanid-loaded nanoparticles for global health applications. In both the case of cannabidiol and delamanid, the nanoparticle formulations greatly enhanced in vitro dissolution kinetics. Comparative studies formulating cannabidiol and delamanid as amorphous solid dispersions highlighted the advantages of nanoparticles for solubility enhancement and physical stability. We also applied FNP to a family of oral peptides displaying systematic structure and property variations to highlight differences in nanoparticle composition required for successful formulation of hydrophobic and hydrophilic peptides. Lastly, we present a sequential, two-mixer FNP process which temporally separates core precipitation and stabilizer attachment to limit stabilizer entrainment and enable higher core loadings of up to 90%. | |
dc.format.mimetype | application/pdf | |
dc.language.iso | en | |
dc.publisher | Princeton, NJ : Princeton University | |
dc.subject | emulsions | |
dc.subject | encapsulation | |
dc.subject | Flash NanoPrecipitation | |
dc.subject | nanomedicine | |
dc.subject | pharmaceuticals | |
dc.subject.classification | Chemical engineering | |
dc.subject.classification | Pharmaceutical sciences | |
dc.subject.classification | Nanoscience | |
dc.title | Nanoparticle Encapsulation for the Solubility Enhancement of Oral Therapeutics | |
dc.type | Academic dissertations (Ph.D.) | |
pu.date.classyear | 2023 | |
pu.department | Chemical and Biological Engineering | |
Appears in Collections: | Chemical and Biological Engineering |
Files in This Item:
File | Description | Size | Format | |
---|---|---|---|---|
Caggiano_princeton_0181D_14645.pdf | 6.85 MB | Adobe PDF | View/Download |
Items in Dataspace are protected by copyright, with all rights reserved, unless otherwise indicated.