生物相容的聚合物纳米粒子降解并释放货物,以应对生物相关水平的过氧化
Caroline de Gracia Lux1, Shivanjali Joshi-Barr, Trung Nguyen
1Skaggs School of Pharmacy and Pharmaceutical Sciences, Department of NanoEngineering, University of California at San Diego, La Jolla, California 92093, United States.
Journal of the American Chemical Society
|September 6, 2012
概括
新的生物相容聚合物降解并释放药物,以应对过氧化,炎症的标志物. 这一突破使得针对性药物输送到患病组织使用新型H(2) O(2) 敏感纳米粒子.
科学领域:
- 生物材料科学 生物材料科学
- 聚合物化学 聚合物化学
- 药物输送系统 药物输送系统
背景情况:
- 氧化应激,以过氧化 (H(2) O(2)) 积累为标志,将炎症与健康组织区分开来.
- 通过对刺激有反应的系统,可以增强对疾病组织的向药物输送.
- 现有的聚合物药物输送系统对生物相关的H2O2度 (50-100μM) 缺乏灵敏度.
研究的目的:
- 开发新型生物相容的聚合物囊,对低度的过氧化敏感.
- 为有针对性的药物输送应用设计H(2) O(2) 触发的降解和货物释放.
- 为了研究这些聚合物的表现在释放治疗有效载荷在氧化应激的反应.
主要方法:
- 合成两个具有乙烯链接的生物相容聚合物,在与聚合物骨干的连接上有所不同 (直接与以太链接).
- 使用核磁共振 (NMR) 和凝浸透染色学 (GPC) 进行聚合物稳定性和降解动学的表征.
- 从这些聚合物中制备纳米颗粒,以评估H(2) O(2) 触发的货物释放,并评估激活中性粒细胞的性能.
主要成果:
- 这两种聚合物结构都在水溶液中表现出稳定性,并且在暴露于H(2) O(2) 时通过乙烯裂变和随后的子甲基重新排列而降解.
- 与聚合物1相比,具有以太链接的聚合物2呈现出明显更快的骨干降解.
- 聚合物2中的纳米颗粒在10小时内在1毫米H2O2下实现了完整的记者染料释放,而聚合物1的时间为26小时,并且在生物学相关的H2O2水平上显示了选择性释放.
- 聚合物2纳米颗粒在与活性中性粒细胞化后释放的量增加了2倍,这表明有针对性的响应能力.
结论:
- 开发了新型生物相容的聚合物囊,该囊会降解并释放货物,以应对生物相关度的过氧化.
- 以乙烯结合的聚合物 (聚合物2) 提供了优异的H(2) O(2) 触发的降解特征,使有效和选择性的药物释放成为可能.
- 这些对H2O2敏感的聚合物代表了先进的,有针对性的药物输送系统的有希望的平台,这些药物降解为安全的副产品.
相关概念视频
Site-Targeted Drug Delivery Systems: Polymeric Carriers
Polymeric carriers enhance targeted drug delivery by increasing efficacy while minimizing off-target effects. These carriers comprise a biodegradable polymeric backbone integrated with functional elements that enable targeting, improve physicochemical properties, and regulate drug release.Targeting MechanismsThe targeting ability of polymeric carriers is mediated by a homing device, which is a molecular recognition component designed to selectively bind to specific tissues or cells. Monoclonal...
Modified-Release Drug Delivery Systems: Stimuli-Activated
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 called...
Bioplastics
Bioplastics derived from microbial processes present a sustainable alternative to conventional petroleum-based plastics. Among these, polyhydroxyalkanoates (PHAs), particularly polyhydroxybutyrates (PHBs), have emerged as prominent candidates due to their biodegradability and biocompatibility. These polymers are synthesized by a variety of bacteria, such as Cupriavidus necator and Pseudomonas putida, which naturally accumulate PHAs as intracellular carbon and energy reserves, especially under...
Peroxisomes
Peroxisomes are specialized organelles present in fungi, plant, and animal cells. It can vary in number, size, morphology, and activity depending on the type of tissue and the nutritional state of the cell. For example, cells with active lipid metabolism, such as adipocytes, neurons, and hepatocytes, have more peroxisomes than other cells in the body. Besides their primary role in breaking down complex organic molecules, peroxisomes can also synthesize specific macromolecules and participate in...
Bioactivation and Tissue Toxicity
Bioactivation is a metabolic process that transforms less reactive substances into highly reactive metabolites, initiating tissue toxicity. This transformation can lead to various toxic effects, including carcinogenesis and teratogenesis. Reactive metabolites are classified into two main types: electrophiles and free radicals.Electrophiles are electron-deficient species and are produced primarily by the enzyme cytochrome P-450 during the metabolism of compounds containing carbon, nitrogen, or...
Drug Biotransformation: Overview
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...

