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用于有效脑药物递送系统的聚合物胶束的滞留

The Sojourn of Polymeric Micelles for Effective Brain Drug Delivery System.

作者信息

Kaur Prabhjot, Rajput Ankita, Singh Dilpreet, Singh Gurdeep, Mehra Anshula, Kaur Sarabjit, Bedi Neena, Arora Saroj

机构信息

Department of Botanical and Environmental Sciences, Guru Nanak Dev University, Amritsar, 143005, India.

Department of Pharmaceutics, ISF College of Pharmacy, Moga, 142001, India.

出版信息

Curr Drug Deliv. 2024;21(1):65-79. doi: 10.2174/1567201820666230413082352.

Abstract

The brain is a delicate organ and targeting neurological diseases with conventional approaches is still a daunting task. This is due to the presence of necessary physiological barriers, mainly the blood-brain barrier, that blocks the entry of dangerous and poisonous substances from the bloodstream, thus helping in maintaining homeostasis. Furthermore, the presence of multidrug resistance transporters which act by prohibiting the entry of drugs across the cell membrane and by channelizing them to the outside environment is another defense mechanism. Despite the advancements in the understanding of disease pathology, only a restricted number of drugs and drug therapies can treat and target neurological diseases. To overcome this shortcoming, the therapeutic approach using amphiphilic block copolymers - using polymeric micelles has gained momentum because of its wide applications like drug targeting, delivery, and imaging. Polymeric micelles are nanocarriers that arise when amphiphilic block copolymers spontaneously assemble in aqueous solutions. The hydrophobic core-hydrophilic shell configuration of these nanoparticles makes it easier to load hydrophobic drugs into the core and as a result, the solubility of these medications is improved. Micelle-based drug delivery carriers can target the brain with reticuloendothelial system uptake and produce a long-circulating effect. PMs can also be combined with targeting ligands that increase their uptake by specific cells and thus decreasing off-target effects. In the present review, we primarily focused on polymeric micelles for brain delivery along with the method of preparation, mechanism of micelle formulation, and the ongoing formulations under clinical trials for brain delivery.

摘要

大脑是一个脆弱的器官,用传统方法治疗神经系统疾病仍然是一项艰巨的任务。这是因为存在必要的生理屏障,主要是血脑屏障,它能阻止危险和有毒物质从血液中进入,从而有助于维持体内平衡。此外,多药耐药转运蛋白的存在也是一种防御机制,它通过阻止药物跨细胞膜进入并将其导向外部环境来发挥作用。尽管在疾病病理学的理解方面取得了进展,但只有数量有限的药物和药物疗法能够治疗和靶向神经系统疾病。为了克服这一缺点,使用两亲性嵌段共聚物——即聚合物胶束的治疗方法因其在药物靶向、递送和成像等广泛应用而受到关注。聚合物胶束是两亲性嵌段共聚物在水溶液中自发组装时形成的纳米载体。这些纳米颗粒的疏水核心-亲水外壳结构使得将疏水药物加载到核心中变得更容易,结果这些药物的溶解度得到了提高。基于胶束的药物递送载体可以通过网状内皮系统摄取靶向大脑并产生长循环效应。聚合物胶束还可以与靶向配体结合,增加其被特定细胞摄取,从而减少脱靶效应。在本综述中,我们主要关注用于脑递送的聚合物胶束,以及其制备方法、胶束形成机制和正在进行的脑递送临床试验配方。

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