药物考虑和代谢命运的腹腔脂质纳米颗粒剂量形式的药物考虑和代谢命运
David F Driscoll1, Bruce R Bistrian2
1Stable Solutions LLC, Easton, MA, USA; UMASS Chan Medical School, Worcester, MA, USA.
Journal of pharmaceutical sciences
|April 30, 2024
概括
脂质纳米粒子 (LNP) 药物输送系统的物理稳定性至关重要. 需要新的方法来准确测量LNP粒子大小分布,并确保这些重要的治疗方法的安全性和有效性.
科学领域:
- 制药科学 制药科学
- 纳米技术 纳米技术
- 药物运输 药物运输 药物运输
背景情况:
- 通过分散剂进行门药物递送,可提供卓越的生物可用性.
- 已建立的药典方法存在于脂质可注射乳液 (迷你乳液),但不是基于脂质纳米粒子 (LNP) 的微乳液.
- 几种基于LNP的药物,包括mRNA疫苗,已获得批准,对mRNA疗法越来越感兴趣.
研究的目的:
- 突出了对基于LNP的微乳液物理稳定性的药典指导的迫切需要.
- 强调开发LNP分散的可靠分析方法的重要性.
- 为了解决测量LNP粒子大小分布 (PSD) 的挑战.
主要方法:
- 讨论了通过粒子聚变或PSD更大的直径尾巴的生长来检测分散中的不稳定性的一般原则.
- 建议对单粒子光学传感技术进行修改光学检测设计的必要性.
- 建议扩大用于光灭和光散射方法的低粒子检测极限.
主要成果:
- 分散的不稳定性由粒子聚变或PSD大直径尾巴的生长表明.
- 目前的药库方法对于基于LNP的微乳液是不够的.
- 已有修改的光学检测技术可用于满足LNP的定量分析要求.
结论:
- 精确测量LNP粒子大小分布对于确保基于LNP的治疗方法的物理稳定性,安全性和有效性至关重要.
- 对于LNP分散,需要制定药库标准和先进的分析技术.
- 现有的技术可以为LNP物理稳定性评估提供必要的定量分析.
相关概念视频
Biopharmaceutics and Pharmacokinetics: Overview
2.0K
Understanding drugs, drug products, and their performance in pharmaceutical science is pivotal. Drugs, whether simple molecules or complex compounds, are designed to interact with the body's biological systems to diagnose, treat, or prevent diseases. Drug products include various delivery systems such as tablets, capsules, injections, and inhalers. The performance of these drug products is gauged by their ability to deliver the active ingredient to the desired site of action at the...
2.0K
Factors Affecting Dissolution: Drug pKa, Lipophilicity and GI pH
1.3K
Drug absorption within the gastrointestinal (GI) tract is a complex process influenced by several critical factors, including the site pH, the drug's dissociation constant (pKa), and the drug's lipophilicity. The GI tract exhibits a pH gradient, with an acidic environment in the stomach and a more alkaline environment in the small intestine. This pH variation directly affects the ionization state of drugs.
A drug's pKa and the pH of the gastrointestinal (GI) tract play crucial roles...
A drug's pKa and the pH of the gastrointestinal (GI) tract play crucial roles...
1.3K
Pharmacokinetics: Overview
6.3K
Pharmacokinetics is a scientific discipline that focuses on the journey of a drug within the body, encompassing four key stages: absorption, distribution, metabolism, and elimination. The first stage, absorption, involves the drug's transfer into the bloodstream. Several factors dictate the extent and speed of this process. For example, the liver often metabolizes oral drugs before they reach systemic circulation, leading to only partial absorption. In contrast, intravenous (IV)...
6.3K
Routes of Drug Administration: Parenteral
1.9K
The administration of drugs via parenteral routes allows for direct drug introduction into the systemic circulation, resulting in high bioavailability because the medication bypasses the harsh conditions of the gastrointestinal tract and hepatic metabolism.
The intravenous route (IV) of drug administration can be further categorized into two types. The bolus injection administers the entire dose rapidly, while an intravenous infusion slowly delivers smaller doses steadily.
The IV route is often...
The intravenous route (IV) of drug administration can be further categorized into two types. The bolus injection administers the entire dose rapidly, while an intravenous infusion slowly delivers smaller doses steadily.
The IV route is often...
1.9K
Factors Affecting Drug Response: Overview
2.0K
When it comes to infants and young children, they are typically administered smaller doses of medication in comparison to adults. This is primarily because their organ functions still need to fully develop, meaning their bodies are not as efficient at metabolizing or eliminating drugs. Additionally, their blood-brain barrier is more permeable than in adults. As a result, high concentrations of drugs can easily penetrate the central nervous system (CNS), potentially leading to neurological...
2.0K
Factors Affecting Drug Distribution: Organ Perfusion Rate
124
Drug distribution within the body is a complex process influenced by several factors, including perfusion rate, the rate at which the bloodstream transports drugs to tissue. This limitation becomes particularly significant when dealing with highly lipophilic drugs. In such cases, the rate at which the drug can move across membranes is crucial, and if the membrane is highly permeable to the drug, distribution becomes rate-limited by perfusion.
Perfusion rate-limited distribution relies on the...
Perfusion rate-limited distribution relies on the...
124


