基于半化中蛋白质粉悬浮的局部眼部蛋白质输送
Christoph Marschall1, Julia Filster2, Madlen Witt3
1Ludwig-Maximilians-Universität München, Department of Pharmacy, Pharmaceutical Technology and Biopharmaceutics, Butenandtstraße 5, D-81377 München, Germany; AbbVie Deutschland GmbH, Knollstraße 50, D-67061 Ludwigshafen, Germany.
概括
新的半化基悬浮物改善局部眼部蛋白质输送,增强药物透和稳定性,用于治疗视网膜疾病等眼睛疾病.
科学领域:
- 眼科医生 眼科 眼科
- 药物运输 药物运输 药物运输
- 生物化学 生物化学
背景情况:
- 眼部疾病,特别是视网膜疾病,可以有效地用蛋白质药物治疗.
- 局部眼部蛋白质配方为角膜和结膜疾病的眼内注射提供了一个有希望的替代方案.
- 局部眼部蛋白质输送的挑战包括药物透率差和稳定性有限.
研究的目的:
- 为了评估半化 (F6H8) 悬浮剂对增强局部眼部蛋白质递送.
- 评估F6H8悬浮物对蛋白质稳定性和角膜透的影响.
- 为了研究F6H8悬浮剂和透增强剂的协同作用.
主要方法:
- 使用模型单克隆抗体 (mAb) 和Fab片段的ex vivo角膜透试验.
- 在F6H8中配制蛋白质悬浮剂,并与水溶液进行比较.
- 用不同度的甲酸盐增强透性的评估.
- 在实验室中使用分层的人类角质细胞进行眼睛刺激测试.
- 在F6H8悬浮剂中对贝瓦齐祖马布的长期稳定性研究.
主要成果:
- 与水溶液相比,F6H8中的蛋白粉悬浮物显著增加了角膜透率.
- 甲酸的透度提高,在F6H8悬浮物中效果更为明显 (Fab片段高达31倍,mAb为13倍).
- 在F6H8悬浮剂中,通过较低的增强剂度实现了可比的透增强.
- 在F6H8中的贝瓦西祖马布悬浮物表现出优越的长期稳定性,而不是市场上的水溶液.
- 测试的配方在角质细胞模型中没有显示眼睛刺激.
结论:
- 半化基悬浮物是局部眼部蛋白质输送的有希望的非水性载体.
- 这种方法增强了蛋白质的透和稳定性,克服了眼部药物输送的关键挑战.
- F6H8悬浮剂,特别是透增强剂,为改善眼表面和视网膜疾病的治疗提供了潜在的策略.
相关概念视频
01:45Overview of Protein Sorting and Transport
Eukaryotic cells have different membrane-bound organelles with distinct protein requirements. The process by which proteins are targeted to a specific organelle is called protein sorting.
Protein sorting can be of two types: signal-based sorting and vesicle-based trafficking. In signal-based sorting, specific amino acid sequences called sorting signals target proteins to the proper location inside the cell either via gated transport or by protein translocation. In gated transport, folded...
Protein sorting can be of two types: signal-based sorting and vesicle-based trafficking. In signal-based sorting, specific amino acid sequences called sorting signals target proteins to the proper location inside the cell either via gated transport or by protein translocation. In gated transport, folded...
01:34Nuclear Protein Sorting
Nuclear protein sorting is the selective trafficking of histones, polymerases, gene regulatory proteins into the nucleus and exporting RNAs and ribosomes to the cytosol. It is a tightly controlled process that regulates gene expression within a cell.
Proteins targeted to the nucleus carry nuclear localization signals or NLS recognized by import receptors in the cytosol. Similarly, proteins with nuclear export signals are recognized by export receptors. Import and export receptors are...
Proteins targeted to the nucleus carry nuclear localization signals or NLS recognized by import receptors in the cytosol. Similarly, proteins with nuclear export signals are recognized by export receptors. Import and export receptors are...
00:59COP Coated Vesicles
Membrane-enclosed structures called vesicles transport proteins and lipids across the cell. The vesicles derive their cargo from the plasma membrane, Golgi, ER, or endosome. Coated vesicles are spherical, protein-coated carriers with a 50–100 nm diameter that mediate bidirectional transport between the ER and the Golgi. The distribution of proteins between the ER and Golgi complex is dynamic and is maintained by different coated vesicles. Their formation is driven by the assembly of different...
01:45Vesicular Tubular Clusters
After budding out from the ER membrane, some COPII vesicles lose their coat and fuse with one another to form larger vesicles and interconnected tubules called vesicular tubular clusters or VTCs. These clusters constitute a compartment at the ER-Golgi interface known as ERGIC (Endoplasmic Reticulum Golgi Intermediate Compartment). The ERGIC is a mobile membrane-bound cargo transport system that sorts proteins secreted from ER and delivers them to the Golgi.
With the help of motor proteins such...
With the help of motor proteins such...
01:28Protein Translocation Machinery on the ER Membrane
The translocon complex situated on the ER membrane is the main gateway for the protein secretory pathway. It facilitates the transport of nascent peptides into the ER lumen and their insertion into the ER membrane.
Sec61 protein conducting channel
In eukaryotes, the translocon complex comprises a core heterotrimeric translocator channel called the Sec61 complex. This channel includes three transmembrane proteins, Sec61α, Sec61β, and Sec61γ, and is the largest subunit of the translocon complex.
Sec61 protein conducting channel
In eukaryotes, the translocon complex comprises a core heterotrimeric translocator channel called the Sec61 complex. This channel includes three transmembrane proteins, Sec61α, Sec61β, and Sec61γ, and is the largest subunit of the translocon complex.
01:26Bacterial Translocation and Protein Secretion
Bacterial protein secretion involves translocation systems to ensure proteins reach their designated locations, including the plasma membrane, periplasm, outer membrane, or the external environment. These translocation systems are vital for bacterial physiology, supporting processes like membrane assembly, enzymatic activity in the periplasm, and interactions with the external environment. The division of labor between Sec and Tat pathways ensures efficiency in handling proteins with diverse...