자료유형  

 학위논문

Control Number  

0016932462

International Standard Book Number  

9798379721053

Dewey Decimal Classification Number  

660

Main Entry-Personal Name  

Caggiano, Nicholas Joseph, III.

Publication, Distribution, etc. (Imprint  

[S.l.] : Princeton University., 2023

Publication, Distribution, etc. (Imprint  

Ann Arbor : ProQuest Dissertations & Theses, 2023

Physical Description  

1 online resource(251 p.)

General Note  

Source: Dissertations Abstracts International, Volume: 84-12, Section: B.

General Note  

Advisor: Priestley, Rodney D.;Prud'homme, Robert K.

Dissertation Note  

Thesis (Ph.D.)--Princeton University, 2023.

Restrictions on Access Note  

This item must not be sold to any third party vendors.

Summary, Etc.  

요약Nanoparticle 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%.

Subject Added Entry-Topical Term  

Chemical engineering.

Subject Added Entry-Topical Term  

Pharmaceutical sciences.

Subject Added Entry-Topical Term  

Nanoscience.

Index Term-Uncontrolled  

Emulsions

Index Term-Uncontrolled  

Encapsulation

Index Term-Uncontrolled  

Nanomedicine

Index Term-Uncontrolled  

Pharmaceuticals

Added Entry-Corporate Name  

Princeton University Chemical and Biological Engineering

Host Item Entry  

Dissertations Abstracts International. 84-12B.

Host Item Entry  

Dissertation Abstract International

Electronic Location and Access  

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Control Number  

joongbu:640396