Laboratory of Pharmaceutical Technology, Dept. of Pharmacy, School of Health Sciences, University of Patras, 26510 Rio, Greece.
Institute of Chemical Engineering Sciences of the Foundation for Research and Technology Hellas (FORTH/IEC-HT), 26504 Rio Patras, Greece.
Molecules. 2019 Apr 18;24(8):1540. doi: 10.3390/molecules24081540.
Amyloid β (Aβ) species are considered as potential targets for the development of diagnostics/therapeutics towards Alzheimer's disease (AD). Nanoliposomes which are decorated with molecules having high affinity for Aβ species may be considered as potential carriers for AD theragnostics. Herein, benzothiazolyl (BTH) decorated nanoliposomes were prepared for the first time, after synthesis of a lipidic BTH derivative (lipid-BTH). The synthetic pathway included acylation of bis(2-aminophenyl) disulfide with palmitic acid or palmitoyl chloride and subsequent reduction of the oxidized dithiol derivative. The liberated thiols were able to cyclize to the corresponding benzothiazolyl derivatives only after acidification of the reaction mixture. Each step of the procedure was monitored by HPLC analysis in order to identify all the important parameters for the formation of the BTH-group. Finally, the optimal methodology was identified, and was applied for the synthesis of the lipid-BTH derivative. BTH-decorated nanoliposomes were then prepared and characterized for physicochemical properties (size distribution, surface charge, physical stability, and membrane integrity during incubation in presence of buffer and plasma proteins). Pegylated BTH-nanoliposomes were demonstrated to have high integrity in the presence of proteins (in comparison to non-peglated ones) justifying their further exploitation as potential theragnostic systems for AD.
淀粉样蛋白 β（Aβ）被认为是开发阿尔茨海默病（AD）诊断和治疗方法的潜在靶点。用对 Aβ 具有高亲和力的分子修饰的纳米脂质体可以被认为是 AD 治疗学的潜在载体。本文首次制备了苯并噻唑基（BTH）修饰的纳米脂质体，该脂质体是通过合成脂质 BTH 衍生物（脂质-BTH）得到的。合成途径包括用棕榈酸或棕榈酰氯对双（2-氨基苯基）二硫醚进行酰化，然后还原氧化的二硫醇衍生物。只有在反应混合物酸化后，游离的硫醇才能环化成相应的苯并噻唑衍生物。为了确定形成 BTH 基团的所有重要参数，对该过程的每个步骤都进行了 HPLC 分析监测。最后，确定了最佳的方法，并将其应用于脂质-BTH 衍生物的合成。然后制备并表征了 BTH 修饰的纳米脂质体的物理化学性质（粒径分布、表面电荷、物理稳定性以及在缓冲液和血浆蛋白存在下孵育时的膜完整性）。与非聚乙二醇化的纳米脂质体相比，聚乙二醇化的 BTH-纳米脂质体在存在蛋白质的情况下具有更高的完整性，这证明了它们可进一步作为 AD 的潜在治疗学系统进行开发。
