助剂在脂质纳米颗粒代谢中的作用:对增强治疗效果的影响
Karlene L M Knaggs1, Yikai Sun1, Brianna A Walz1
1Institute of Biomedical Engineering, University of Toronto, Toronto, ON, Canada.
Therapeutic delivery
|May 29, 2025
概括
脂质纳米粒子 (LNP) 对于核酸输送至关重要. 本次审查侧重于LNP成分化学和配方,以提高安全性,生物降解性和减少炎症,以改善药物输送.
科学领域:
- 生物技术是生物技术.
- 药物输送系统 药物输送系统
- 纳米医学是一种纳米医学.
背景情况:
- 脂质纳米颗粒 (LNP) 是核酸的关键输送载体,由电离性脂质,脂质,胆固醇和脂质聚乙烯糖醇组成.
- LNP的组成和比例极大地影响了核酸输送效率和器官向.
- 配送后的命运,包括LNP组件的降解,清除和保留,显著影响耐受性和安全性.
研究的目的:
- 审查LNP成分化学和配方对其体内命运的影响.
- 通过分子修改和配方优化突出提高LNP耐受性和安全性的策略.
- 为设计LNP组件提供可预测的新陈代谢和减少不良影响的见解.
主要方法:
- 对LNP组成,功能和体内行为现有文献的综述.
- 对可离子化脂质,脂质聚乙烯糖醇和核酸的化学变化的分析.
- 讨论配方策略,包括胆固醇和脂含量,以优化清除和生物降解性.
主要成果:
- 缓慢降解的电离性脂质可以导致长时间的炎症反应.
- 对LNP组件的分子修改可以提高耐受性和安全性.
- 配方策略,如调整胆固醇和脂量,可以提高生物降解性和减少炎症.
结论:
- 设计具有改善新陈代谢和生物降解性的LNP组件对于提高药物输送安全性和有效性至关重要.
- 了解每个LNP成分的降解和清除途径对于预测体内行为至关重要.
- 未来的研究应该专注于开发新的LNP化学物质和配方,以最大限度地减少非目标效应并促进有效的清除.
相关概念视频
Factors Affecting Dissolution: Particle Size and Effective Surface Area
1.1K
Dissolution kinetics, an essential aspect of oral drug delivery, is significantly influenced by the drug's particle size. According to the Noyes-Whitney dissolution model, the dissolution rate correlates directly with the drug's surface area. The larger the surface area, the higher the drug's solubility in water, leading to a faster drug dissolution rate. Reducing particle size increases the effective surface area, enhancing the dissolution process. Micronization and nanosizing are...
1.1K
Factors Influencing Drug Absorption: Pharmaceutical Parameters
198
Solid dosage forms such as tablets and capsules undergo rigorous manufacturing processes to ensure stability and effectiveness. Their dissolution and absorption properties are influenced significantly by the choice of excipients (inactive ingredients that serve various roles in the formulation), and the methodology applied during production. The manufacturing parameters, such as compression force and granulation techniques, significantly affect dissolution rates. Elevated compression forces...
198
Factors Affecting Dissolution: Drug Permeability, Stability and Stereochemistry
269
Orally administered drugs primarily enter the systemic circulation via passive diffusion through the intestinal membranes. The drug's absorption is influenced by drug stability in the gastrointestinal GI tract, membrane permeability, the surface area available for absorption, luminal drug concentration, and residence time in the lumen. Drug permeability can be enhanced by adjusting the lipophilicity, polarity, or molecular size of the drug, promoting its passive transport across intestinal...
269
Drug Biotransformation: Overview
3.0K
Pharmaceutical substances known as xenobiotics are predominantly lipophilic and nonionized. This enables them to permeate lipid bilayers, such as cell membranes, and interact with intracellular target receptors. Lipophilic drugs have an advantage in crossing biological barriers and reaching their intended sites of action. However, lipophilic drugs often have a restricted capacity for renal expulsion or elimination from the body. When these drugs enter the kidneys and undergo glomerular...
3.0K
Factors Affecting Drug Biotransformation: Physicochemical and Chemical Properties of Drugs
393
A drug's physicochemical properties fundamentally influence its metabolism. For instance, a drug's molecular size and shape critically determine its interaction with enzymes and transporters — larger drugs may face difficulty reaching enzyme active sites, altering their metabolic pathways. The pKa of a drug, which establishes its ionization state, can impact its solubility and absorption, thereby influencing metabolism.
The drug's acidity or basicity is essential in...
The drug's acidity or basicity is essential in...
393
Factors Affecting Drug Biotransformation: Biological
260
Biological factors significantly impact drug metabolism, influencing drug clearance, efficacy, and potential toxicity.
Species differences: Variations in enzyme systems across species can cause disparities in drug metabolism. For instance, humans may metabolize certain drugs faster than rodents, altering therapeutic effects.
Strain differences: Genetic variations within a species can result in differing enzyme activity, impacting drug response and toxicity. For example, some mouse strains may...
Species differences: Variations in enzyme systems across species can cause disparities in drug metabolism. For instance, humans may metabolize certain drugs faster than rodents, altering therapeutic effects.
Strain differences: Genetic variations within a species can result in differing enzyme activity, impacting drug response and toxicity. For example, some mouse strains may...
260


