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Role of Surfactants in the Stabilization of Protein Formulations
Role of Surfactants in the Stabilization of Protein Formulations
상세정보
- 자료유형
- 학위논문 서양
- 최종처리일시
- 20260202102943
- ISBN
- 9798290916941
- DDC
- 615
- 저자명
- Li, Jinghan.
- 서명/저자
- Role of Surfactants in the Stabilization of Protein Formulations
- 발행사항
- [Sl] : University of Minnesota, 2024
- 발행사항
- Ann Arbor : ProQuest Dissertations & Theses, 2024
- 형태사항
- 143 p
- 주기사항
- Source: Dissertations Abstracts International, Volume: 87-02, Section: B.
- 주기사항
- Advisor: Suryanarayanan, Raj.
- 학위논문주기
- Thesis (Ph.D.)--University of Minnesota, 2024.
- 초록/해제
- 요약Surfactants are widely used in protein formulations to mitigate interfacial stresses. In aqueous solutions, the stabilization effect of surfactants is brought out by competitively replacing proteins from surface adsorption, and by interacting with proteins to reduce their aggregation propensity. There are three surfactants used in protein products - polysorbate 20 and 80 (PS20 and PS80) as well as poloxamer 188 (P188). The first objective of this thesis was to compare the stabilization effect of these surfactants on a model protein, lactate dehydrogenase (LDH). The dynamic surface tension analysis results showed that polysorbates were more effective than P188 in preventing LDH surface adsorption and effectively stabilized LDH against mechanical stress during shaking. However, based on near UV circular dichroism results, polysorbates perturbed LDH higher order structure through hydrophobic interaction and accelerated protein destabilization during quiescent incubation, while P188 did not have such an adverse effect. In frozen and freeze-dried protein formulations, surfactants are used to prevent ice surface-induced protein destabilization. Thus, the second objective was to investigate the stabilization effect of surfactants in frozen protein solutions, and to study the impact of surfactant phase transformation (i.e., crystallization) on protein stability. The phase behavior of surfactants was studied using synchrotron X-ray diffractometry and differential scanning calorimetry. Similar to polysorbates, P188 was effective in preventing ice surface-induced LDH destabilization. However, P188 crystallization undermined its stabilization function when used at a low concentration. The addition of noncrystallizing solutes, such as protein and sugar, by inhibiting surfactant crystallization, improved its function as a stabilizer in frozen solutions. Overall, P188 can be an alternative surfactant to polysorbates in preventing ice surface-induced protein destabilization. In addition, the high crystallization propensity of P188 renders it an additional functionality as a bulking agent in freeze-dried formulations, ensuring elegant lyophiles. The third objective aims to explore the dual functionality of P188 - a stabilizer in frozen solutions and a bulking agent in lyophiles. During lyophilization, the surfactant substantially crystallized upon drying, providing elegant freeze-dried cakes. However, P188 alone did not function as a lyoprotectant and had to be used in combination with a sugar. Overall, the thesis highlights the importance of surfactants in stabilizing protein against interfacial stress, and the multifunctionality of P188, an alternative candidate to polysorbates, in frozen and freeze-dried formulations.
- 일반주제명
- Pharmaceutical sciences
- 일반주제명
- Medicine
- 일반주제명
- Biochemistry
- 일반주제명
- Biomechanics
- 키워드
- Freezing
- 키워드
- Lyophilization
- 키워드
- Protein
- 키워드
- Stability
- 키워드
- Surfactant
- 기타저자
- University of Minnesota Pharmaceutics
- 기본자료저록
- Dissertations Abstracts International. 87-02B.
- 전자적 위치 및 접속
- 로그인 후 원문을 볼 수 있습니다.
MARC
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■020 ▼a9798290916941
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■040 ▼aMiAaPQ▼cMiAaPQ
■0820 ▼a615
■1001 ▼aLi, Jinghan.
■24510▼aRole of Surfactants in the Stabilization of Protein Formulations
■260 ▼a[Sl]▼bUniversity of Minnesota▼c2024
■260 1▼aAnn Arbor▼bProQuest Dissertations & Theses▼c2024
■300 ▼a143 p
■500 ▼aSource: Dissertations Abstracts International, Volume: 87-02, Section: B.
■500 ▼aAdvisor: Suryanarayanan, Raj.
■5021 ▼aThesis (Ph.D.)--University of Minnesota, 2024.
■520 ▼aSurfactants are widely used in protein formulations to mitigate interfacial stresses. In aqueous solutions, the stabilization effect of surfactants is brought out by competitively replacing proteins from surface adsorption, and by interacting with proteins to reduce their aggregation propensity. There are three surfactants used in protein products - polysorbate 20 and 80 (PS20 and PS80) as well as poloxamer 188 (P188). The first objective of this thesis was to compare the stabilization effect of these surfactants on a model protein, lactate dehydrogenase (LDH). The dynamic surface tension analysis results showed that polysorbates were more effective than P188 in preventing LDH surface adsorption and effectively stabilized LDH against mechanical stress during shaking. However, based on near UV circular dichroism results, polysorbates perturbed LDH higher order structure through hydrophobic interaction and accelerated protein destabilization during quiescent incubation, while P188 did not have such an adverse effect. In frozen and freeze-dried protein formulations, surfactants are used to prevent ice surface-induced protein destabilization. Thus, the second objective was to investigate the stabilization effect of surfactants in frozen protein solutions, and to study the impact of surfactant phase transformation (i.e., crystallization) on protein stability. The phase behavior of surfactants was studied using synchrotron X-ray diffractometry and differential scanning calorimetry. Similar to polysorbates, P188 was effective in preventing ice surface-induced LDH destabilization. However, P188 crystallization undermined its stabilization function when used at a low concentration. The addition of noncrystallizing solutes, such as protein and sugar, by inhibiting surfactant crystallization, improved its function as a stabilizer in frozen solutions. Overall, P188 can be an alternative surfactant to polysorbates in preventing ice surface-induced protein destabilization. In addition, the high crystallization propensity of P188 renders it an additional functionality as a bulking agent in freeze-dried formulations, ensuring elegant lyophiles. The third objective aims to explore the dual functionality of P188 - a stabilizer in frozen solutions and a bulking agent in lyophiles. During lyophilization, the surfactant substantially crystallized upon drying, providing elegant freeze-dried cakes. However, P188 alone did not function as a lyoprotectant and had to be used in combination with a sugar. Overall, the thesis highlights the importance of surfactants in stabilizing protein against interfacial stress, and the multifunctionality of P188, an alternative candidate to polysorbates, in frozen and freeze-dried formulations.
■590 ▼aSchool code: 0130.
■650 4▼aPharmaceutical sciences
■650 4▼aMedicine
■650 4▼aBiochemistry
■650 4▼aBiomechanics
■653 ▼aFreezing
■653 ▼aLyophilization
■653 ▼aProtein
■653 ▼aStability
■653 ▼aSurfactant
■690 ▼a0572
■690 ▼a0564
■690 ▼a0487
■690 ▼a0648
■71020▼aUniversity of Minnesota▼bPharmaceutics.
■7730 ▼tDissertations Abstracts International▼g87-02B.
■790 ▼a0130
■791 ▼aPh.D.
■792 ▼a2024
■793 ▼aEnglish
■85640▼uhttp://www.riss.kr/pdu/ddodLink.do?id=T17356520▼nKERIS▼z이 자료의 원문은 한국교육학술정보원에서 제공합니다.
