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Expanding the Repertoire of Poly(Oxazoline) Functionality
Expanding the Repertoire of Poly(Oxazoline) Functionality
상세정보
- 자료유형
- 학위논문 서양
- 최종처리일시
- 20250211152941
- ISBN
- 9798896074649
- DDC
- 540
- 서명/저자
- Expanding the Repertoire of Poly(Oxazoline) Functionality
- 발행사항
- [Sl] : University of California, Los Angeles, 2024
- 발행사항
- Ann Arbor : ProQuest Dissertations & Theses, 2024
- 형태사항
- 307 p
- 주기사항
- Source: Dissertations Abstracts International, Volume: 86-04, Section: B.
- 주기사항
- Advisor: Sletten, Ellen M.
- 학위논문주기
- Thesis (Ph.D.)--University of California, Los Angeles, 2024.
- 초록/해제
- 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.
- 일반주제명
- Chemistry
- 일반주제명
- Polymer chemistry
- 일반주제명
- Pharmaceutical sciences
- 일반주제명
- Analytical chemistry
- 일반주제명
- Nanoscience
- 키워드
- Poly(oxazoline)
- 키워드
- Polymers
- 키워드
- Surfactants
- 기타저자
- University of California, Los Angeles Chemistry 0153
- 기본자료저록
- Dissertations Abstracts International. 86-04B.
- 전자적 위치 및 접속
- 로그인 후 원문을 볼 수 있습니다.
MARC
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■00520250211152941
■006m o d
■007cr#unu||||||||
■020 ▼a9798896074649
■035 ▼a(MiAaPQ)AAI31565046
■040 ▼aMiAaPQ▼cMiAaPQ
■0820 ▼a540
■1001 ▼aGarcia, Joseph Angel.
■24510▼aExpanding the Repertoire of Poly(Oxazoline) Functionality
■260 ▼a[Sl]▼bUniversity of California, Los Angeles▼c2024
■260 1▼aAnn Arbor▼bProQuest Dissertations & Theses▼c2024
■300 ▼a307 p
■500 ▼aSource: Dissertations Abstracts International, Volume: 86-04, Section: B.
■500 ▼aAdvisor: Sletten, Ellen M.
■5021 ▼aThesis (Ph.D.)--University of California, Los Angeles, 2024.
■520 ▼aWater 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.
■590 ▼aSchool code: 0031.
■650 4▼aChemistry
■650 4▼aPolymer chemistry
■650 4▼aPharmaceutical sciences
■650 4▼aAnalytical chemistry
■650 4▼aNanoscience
■653 ▼aPoly(oxazoline)
■653 ▼aPolymers
■653 ▼aSurfactants
■653 ▼aPharmaceutical industry
■653 ▼aHydrophilic polymers
■690 ▼a0485
■690 ▼a0565
■690 ▼a0486
■690 ▼a0572
■690 ▼a0495
■71020▼aUniversity of California, Los Angeles▼bChemistry 0153.
■7730 ▼tDissertations Abstracts International▼g86-04B.
■790 ▼a0031
■791 ▼aPh.D.
■792 ▼a2024
■793 ▼aEnglish
■85640▼uhttp://www.riss.kr/pdu/ddodLink.do?id=T17164266▼nKERIS▼z이 자료의 원문은 한국교육학술정보원에서 제공합니다.
