三维口腔粘膜等价物作为跨粘膜药物透研究模型
Azra Riaz1,2, Sanna Gidvall1,2, Zdenka Prgomet3
1Biomedical Science, Faculty of Health and Society, Malmö University, 205 06 Malmö, Sweden.
Pharmaceutics
|May 27, 2023
概括
研究人员为药物输送研究开发了先进的口腔粘膜等价物 (OME). 这些3D体外模型模仿人类口腔组织,为药物透测试的传统方法提供了更好的替代方案.
科学领域:
- 组织工程是组织工程.
- 生物材料科学 生物材料科学
- 药理学 药理学是指药理学的学科.
背景情况:
- 口服透管药物管理为药物输送提供了优势.
- 现有的体外模型,如单层培养或动物组织,在模拟体内条件方面存在局限性.
- 3D口腔粘膜等价物 (OME) 之所以有趣,是因为它们能够复制口腔组织结构和细胞分化.
研究的目的:
- 开发OME作为药物透研究的可靠膜.
- 使用人类角质细胞创建全厚和分厚的OME模型.
- 评估已开发的OME的屏障特性和脂质分化.
主要方法:
- 使用OKF6 TERT-2人类角质细胞开发全厚和分厚OME.
- 对屏障功能的横体电阻 (TEER) 的评估.
- 使用 eletriptan 化物作为模型药物的药物透性研究.
- 脂质组成 (胺,脂) 和细胞增殖/细胞亡的分析.
主要成果:
- 开发的OME模型表现出与商业模型相比的TEER值.
- 全厚的OME表现出与商业模型相似的药物流量,表明具有相当的透屏障特性.
- 组织工程OME显示了胺的增加和脂的减少,这表明脂质的分化.
- 分裂厚度的OME模型在21天的空气液体界面显示出最佳的发展,在以后的时间点出现了亡的迹象.
结论:
- 开发的OME模型准确地模拟了用于药物透研究的口腔粘膜屏障特性.
- 组织工程协议成功诱导了OME中的脂质分化.
- 这些OME模型提供了更好的保质期和更广泛的药物应用的潜力,包括长期药物暴露和炎症状况研究.
相关概念视频
Methods for Studying Drug Absorption: In vitro
264
In vitro experiments are crucial for understanding the transport and absorption of drugs through biological materials. These studies employ varied methods such as the diffusion cell method, the everted sac technique, and the everted ring technique.
The diffusion cell method uses a two-compartment cell, including a donor compartment with the drug solution, which simulates the environment where the drug is applied, and a receptor compartment with a buffer solution, which simulates the environment...
The diffusion cell method uses a two-compartment cell, including a donor compartment with the drug solution, which simulates the environment where the drug is applied, and a receptor compartment with a buffer solution, which simulates the environment...
264
Methods for Studying Drug Absorption: In situ
275
In situ experiments, such as the Doluisio method and Single-Pass Perfusion technique, provide critical insights into drug uptake by simulating in vivo conditions for drug absorption.
The Doluisio method involves perfusing a prepared segment of a rat's small intestine with a solution of radiolabeled drug and a non-absorbable marker. This helps to differentiate between absorbed and non-absorbed drug concentrations. The intestinal segment is connected at both ends using tubing and syringes,...
The Doluisio method involves perfusing a prepared segment of a rat's small intestine with a solution of radiolabeled drug and a non-absorbable marker. This helps to differentiate between absorbed and non-absorbed drug concentrations. The intestinal segment is connected at both ends using tubing and syringes,...
275
Factors Affecting Dissolution: Drug Permeability, Stability and Stereochemistry
238
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...
238
Non-Oral Extravascular Drug Absorption Routes
242
Non-oral extravascular routes, which encompass sublingual, buccal, topical, intramuscular, and inhalation methods, primarily utilize passive diffusion to transport drugs into the systemic circulation. The absorption rates and effectiveness of these routes depend on the drug's physicochemical properties, as well as the patient's anatomical and pathophysiological state.
Lipophilic drugs that are stable at salivary pH (6) and exhibit minimal binding to the oral mucosa are absorbed more...
Lipophilic drugs that are stable at salivary pH (6) and exhibit minimal binding to the oral mucosa are absorbed more...
242
Drug Delivery: Enteral Route
528
The enteral drug administration involves three primary routes: oral, sublingual, and buccal. Oral ingestion is the most prevalent, safe, economical, and convenient method for drug administration. However, it has certain drawbacks, including limited absorption due to the drug's low water solubility or poor membrane permeability, possible emesis from GI mucosa irritation, destruction of drugs by digestive enzymes or low gastric pH, and irregular absorption along with food or other drugs.
528
Noncompartmental Analysis: Mean Transit, Absorption and Dissolution Time
126
When drugs are administered extravascularly, a comprehensive evaluation through noncompartmental analysis becomes imperative. This analytical approach considers various parameters that play a crucial role in understanding the pharmacokinetics of these drugs.
One of the key parameters is the mean transit time (MTT), which refers to the total duration required for drug molecules to transit through the body. MTT is determined by calculating the ratio of the area under the moment curve to the area...
One of the key parameters is the mean transit time (MTT), which refers to the total duration required for drug molecules to transit through the body. MTT is determined by calculating the ratio of the area under the moment curve to the area...
126


