자료유형  

 학위논문

Control Number  

0017164266

International Standard Book Number  

9798896074649

Dewey Decimal Classification Number  

540

Main Entry-Personal Name  

Garcia, Joseph Angel.

Publication, Distribution, etc. (Imprint  

[S.l.] : University of California, Los Angeles., 2024

Publication, Distribution, etc. (Imprint  

Ann Arbor : ProQuest Dissertations & Theses, 2024

Physical Description  

307 p.

General Note  

Source: Dissertations Abstracts International, Volume: 86-04, Section: B.

General Note  

Advisor: Sletten, Ellen M.

Dissertation Note  

Thesis (Ph.D.)--University of California, Los Angeles, 2024.

Summary, Etc.  

요약Water soluble homopolymers and surfactants are an essential part of current and future therapeutics. They allow for the solubilization of hydrophobic drugs either by covalent attachment to hydrophilic polymers, or through noncovalent encapsulation into nanoparticles by surfactants. With respect to cancer treatment, these nanoparticles can be administered as unfunctionalized packages that will passively accumulate into tumor, or as functionalized packages with either tumor targeting ligands on the outside, or tumor-selective stimuli responsive moieties built within the polymer. The golden standard for hydrophilic polymers in the biomedical field is poly(ethylene) glycol (PEG), a polymer known for its high hydrophilicity, high anti-fouling capabilities, and prolific commercial availability. In part because of the tremendous success seen by PEG, an ever-growing percentage of the population is developing PEG allergies. This was exemplified in the recent Coronavirus pandemic, where a small but non-insignificant number of allergic reactions caused by PEG in the nanoparticle formulation were observed. Thus, there is an ever-growing need to develop alternatives to PEG for use, especially in the pharmaceutical industry.One such alternative to PEG is poly(2-Methyl-2-Oxazoline) (P(MeOx)). P(MeOx) is more hydrophilic than PEG, the size of the polymer can be easily tuned by the reaction stoichiometry, and P(MeOx) is highly functionalizable. While there have been many reports of building functional groups into poly(oxazolines) (P(Ox)s) for various applications, only one P(Ox) based therapeutic is undergoing clinical trials. It is apparent that in order to actualize the claims of P(Ox) being a PEG alternative, functional groups relevant to in vivo and clinical applications need to be installed. This thesis aims to expand the repertoire of POx functionality by installing chemical groups can affect the localization of P(Ox)-stabilized nanoparticles within the body.Chapter 1 is an unpublished perspective on the current state of P(Ox) surfactant functionality, specifically with regards to cancer relevant targeting ligands and stimuli responsive moieties.Chapter 2 details the synthesis of a biotin initiator, with biotin being a ligand of interest for cancer targeting and general chemical biology applications. This initiator was used to polymerize several different P(Ox)s with varying functional groups. The efficacy of these polymers was then evaluated using a set of standard chemical biology techniques.Chapter 3 details the synthesis of acid cleavable P(Ox) based diblock copolymer surfactants. The cleavage kinetics were evaluated both in free polymers and in perfluorocarbon (PFC)-in-water nanoemulsions. Lastly emulsions made from this cleavable surfactant were used to deliver a fluorophore into cells to demonstrate endosomal escape.Chapter 4 describes the synthesis of custom, fluorinated P(MeOx) based surfactants for the purpose of lowering PFC-in-water microdroplet interfacial tensions. The structure-property relationships of polymers of different sizes and block length ratios were evaluated for this purpose.Chapter 5 investigates the role that nanoemulsion charge plays in organ localization in mice. Uncharged, positively charged, and negatively charged emulsions were administered into mice, where their localization was quantified through fluorescence microscopy.

Subject Added Entry-Topical Term  

Chemistry.

Subject Added Entry-Topical Term  

Polymer chemistry.

Subject Added Entry-Topical Term  

Pharmaceutical sciences.

Subject Added Entry-Topical Term  

Analytical chemistry.

Subject Added Entry-Topical Term  

Nanoscience.

Index Term-Uncontrolled  

Poly(oxazoline)

Index Term-Uncontrolled  

Polymers

Index Term-Uncontrolled  

Surfactants

Index Term-Uncontrolled  

Pharmaceutical industry

Index Term-Uncontrolled  

Hydrophilic polymers

Added Entry-Corporate Name  

University of California, Los Angeles Chemistry 0153

Host Item Entry  

Dissertations Abstracts International. 86-04B.

Electronic Location and Access  

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Control Number  

joongbu:657094