从现场形成的脂质体储存库中进行生理控制的释放
Remo Eugster1, Simone Aleandri1, Julia Blandine Bassila2
1Department of Chemistry, Biochemistry and Pharmaceutical Sciences, University of Bern, Bern, Switzerland.
概括
这项研究引入了一种用于控制药物释放的新型热敏脂质体储存 (TILD). TILD提供长达四天的持续治疗药物水平,解决治疗坚持挑战.
科学领域:
- 生物材料科学 生物材料科学
- 药物输送系统 药物输送系统
- 药理学 药理学是指药理学的学科.
背景情况:
- 治疗不良的坚持是全球重要的健康问题,增加了发病率,死亡率和医疗保健费用.
- 控制释放储存提供了一个有希望的策略,以改善患者的遵守,特别是当频繁的剂量是困难的.
- 现有的长效注射配方面临着诸如注射能力差,药物开始延迟和复杂制造等挑战.
研究的目的:
- 开发和表征一种热敏,在位形成脂质体储存 (TILD) 用于调节膜相关药物的释放.
- 评估TILD在皮下注射后持续药物输送的体内性能.
- 用分子模拟来合理设计系统和验证生理暗示响应.
主要方法:
- 热响应性脂肪体储存系统的设计和合成.
- 使用布普伦诺啡因作为释放研究的模式止痛药.
- 采用分子模拟来指导系统设计和预测行为.
- 进行结构和体表征以验证响应性.
- 在老鼠和比格尔犬身上进行体内研究,以评估仓库形成,药物水平和药理动力学.
主要成果:
- 提尔德证明可以调节的药物释放对皮下双价和体温的反应.
- 分子模拟成功指导了热敏脂质体储存库的设计.
- 在体内研究表明,稳定的仓库形成和维持治疗性布普伦诺芬水平在老鼠和狗中长达四天.
- 药理动力学研究证实了老鼠的长时间止痛,验证了该系统的有效性.
结论:
- 热敏反应,在位形成脂质体储存 (TILD) 是持续的皮下药物递送的可行平台.
- 根据生理线索,TILD有效调节药物释放,从而有可能改善治疗坚持.
- 这种新的配方表明了长期作用的膜相关药物的潜力,解决了当前注射疗法的局限性.
相关概念视频
01:19Modified-Release Drug Delivery Systems: Rate-Programmed II
139
Rate-programmed drug delivery systems release drugs in a controlled manner to maintain therapeutic levels. Three main designs include reservoir, matrix, and hybrid systems.Reservoir systems consist of a drug core enclosed within a membrane that controls drug release. In non-swelling reservoir systems, polymers like ethyl cellulose or polymethacrylates are used. These do not hydrate in aqueous media and control release through membrane thickness, porosity, or insolubility. This type includes...
139
01:20Modified-Release Drug Delivery Systems: Influencing Factors
215
Modified-release drug delivery systems are designed to optimize the therapeutic effect of drugs by minimizing side effects, reducing the dosage required, and controlling drug release to align with pharmacokinetic and pharmacodynamic needs. The system depends on two key factors: the drug's release from the formulation and its movement through the body to the target site. Unlike conventional dosage forms, where absorption is the limiting step, the rate of drug release is the key determinant in...
215
01:23Modified-Release Drug Delivery Systems: Classification
318
Modified-release drug delivery systems improve drug efficacy and minimize side effects by controlling the rate and location of drug release. These systems fall into three categories: rate-programmed, stimuli-activated, and site-targeted.Rate-programmed systems release drugs at a predetermined rate, maintaining consistent therapeutic levels and reducing fluctuations that could lead to toxicity or subtherapeutic effects. These systems use polymeric matrices, reservoir-based designs, or osmotic...
318
01:22Modified-Release Drug Delivery Systems: Rate-Programmed I
174
Rate-programmed drug delivery systems (DDS) are designed to release drugs at specific, controlled rates to maintain consistent therapeutic levels. These systems are categorized based on their release mechanisms, including dissolution-controlled DDS, diffusion-controlled DDS, and combined dissolution-diffusion-controlled DDS.In dissolution-controlled DDS, the release rate depends on the slow dissolution of the drug itself or the surrounding matrix. Drugs with inherently slow dissolution rates,...
174
01:30Modified-Release Drug Delivery Systems: Stimuli-Activated
184
Stimuli-activated drug delivery systems are designed to release drugs in response to specific physical, chemical, or biological stimuli. These systems often utilize hydrogels—three-dimensional, hydrophilic polymer networks capable of swelling in aqueous environments and retaining significant fluid volumes. Upon exposure to particular stimuli, these hydrogels undergo structural transitions that allow the embedded drug to be released. Due to this adaptive behavior, such systems are also...
184
01:11Oral Drug Delivery Systems: Delayed-Release Systems
228
Delayed-release drug delivery systems are specialized pharmaceutical formulations designed to postpone the release of active compounds until the drug reaches a specific region of the gastrointestinal (GI) tract, typically the intestine. These systems are essential for drugs that may cause gastric irritation, are unstable in acidic environments, or need to exert therapeutic effects locally in the intestinal or colonic regions.The core feature of delayed-release systems is the use of enteric...
228