Isoglu Ismail Alper, Ozsoy Yıldız, Isoglu Sevil Dincer
Bioengineering Department, Faculty of Life and Natural Sciences, Abdullah Gül University, Kayseri, Turkey.
Faculty of Pharmacy, Istanbul University, Istanbul, Turkey.
Curr Top Med Chem. 2017;17(13):1469-1489. doi: 10.2174/1568026616666161222110600.
There are several barriers that drug molecules encounter in body beginning from kidney filtration and reticulo-endothelial system (RES) clearance to cellular trafficking. Multifunctional nanocarriers have a great potential for the delivery of drugs by enhancing therapeutic activity of existing methodologies. A variety of nanocarriers are constructed by different material types, which have unique physicochemical properties for drug delivery applications. Micelles formed by amphiphilic polymers are one of the most important drug/nanocarrier formulation products, in which the core part is suitable for encapsulation of hydrophobic agent whereas the outer shell can be utilized for targeting the drug to the disease area. Micelles as self-assembled nanostructures may encounter difficulties in biodistribution of encapsulated drugs because they have a tendency to be dissociated in dilution or high ionic strength. Therefore, therapeutic efficiency is decreased and it requires high amount of drug to be administered to achieve more efficient result. To overcome this problem, covalently stabilized structures produced by cross-linking in core or shell part, which can prevent the micelle dissociation and regulate drug release, have been proposed. These systems can be designed as responsive systems in which cross-links are degradable or hydrolysable under specific conditions such as low pH or reductive environment. These are enhancing characteristics in drug delivery because their cleavage allows the release of bioactive agent encapsulated in the carrier at a certain site or time. This review describes the chemical methodologies for the preparation of cross-linked micelles, and reports an update of latest studies in literature.
药物分子在体内会遇到多种屏障，从肾脏滤过、网状内皮系统（RES）清除到细胞转运。多功能纳米载体通过增强现有方法的治疗活性，在药物递送方面具有巨大潜力。多种纳米载体由不同材料类型构建而成，它们在药物递送应用中具有独特的物理化学性质。两亲性聚合物形成的胶束是最重要的药物/纳米载体制剂产品之一，其中核心部分适合封装疏水性药物，而外壳可用于将药物靶向疾病区域。胶束作为自组装纳米结构，在封装药物的生物分布方面可能会遇到困难，因为它们在稀释或高离子强度下有解离的倾向。因此，治疗效率会降低，需要施用大量药物才能获得更有效的结果。为了克服这个问题，人们提出了通过在核心或外壳部分交联产生的共价稳定结构，这种结构可以防止胶束解离并调节药物释放。这些系统可以设计为响应系统，其中交联在特定条件下（如低pH或还原环境）可降解或水解。这些是药物递送中的增强特性，因为它们的裂解允许在特定部位或时间释放封装在载体中的生物活性剂。本文综述了制备交联胶束的化学方法，并报告了文献中最新研究的进展。
