Laboratory of Microscopic Imaging & Specialized Biological Techniques. Faculty of Biology & Environmental Protection. University of Lodz, Banacha 12/16, Lodz 90-237, Poland.
Department of Nuclear Physics and Biophysics, Faculty of Mathematics, Physics and Informatics, Comenius University, 842 48 Bratislava, Slovakia.
Colloids Surf B Biointerfaces. 2023 Jul;227:113371. doi: 10.1016/j.colsurfb.2023.113371. Epub 2023 May 24.
One of the major limitations for the treatment of many diseases is an inability of drugs to cross the cell membrane barrier. Different kinds of carriers are being investigated to improve drug bioavailability. Among them, lipid or polymer-based systems are of special interest due to their biocompatibility. In our study, we combined dendritic and liposomal carriers and analysed the biochemical and biophysical properties of these formulations. Two preparation methods of Liposomal Locked-in Dendrimers (LLDs) systems have been established and compared. Carbosilane ruthenium metallodendrimer was complexed with an anti-cancer drug (doxorubicin) and locked in a liposomal structure, using both techniques. The LLDs systems formed by hydrophilic locking had more efficient transfection profiles and interacted with the erythrocyte membrane better than systems using the hydrophobic method. The results indicate these systems have improved transfection properties when compared to non-complexed components. The coating of dendrimers with lipids significantly reduced their hemotoxicity and cytotoxicity. The nanometric size, low polydispersity index and reduced positive zeta potential of such complexes made them attractive for future application in drug delivery. The formulations prepared by the hydrophobic locking protocol were not effective and will not be considered furthermore as prospective drug delivery systems. In contrast, the formulations formed by the hydrophilic loading method have shown promising results where the cytotoxicity of LLD systems with doxorubicin was more effective against cancer than normal cells.
治疗许多疾病的主要限制之一是药物无法穿过细胞膜屏障。正在研究各种载体以提高药物的生物利用度。其中，由于其生物相容性，基于脂质或聚合物的系统特别受到关注。在我们的研究中，我们结合了树突状和脂质体载体，并分析了这些制剂的生化和物理特性。已经建立并比较了两种脂质体锁定树突状（LLD）系统的制备方法。使用这两种技术，将碳硅烷钌金属树突状化合物与抗癌药物（阿霉素）络合并锁定在脂质体结构中。通过亲水锁定形成的 LLD 系统具有更高的转染效率，并且与红细胞膜的相互作用优于使用疏水性方法的系统。结果表明，与未络合的成分相比，这些系统具有改善的转染特性。用脂质对树突状进行涂层可显著降低其血液毒性和细胞毒性。这些复合物的纳米尺寸，低多分散指数和降低的正 ζ 电位使它们成为药物递送的有吸引力的未来应用。通过疏水性锁定方案制备的制剂没有效果，因此不会进一步被认为是有前途的药物递送系统。相比之下，通过亲水性加载方法形成的制剂显示出有希望的结果，其中阿霉素的 LLD 系统的细胞毒性对癌细胞比对正常细胞更有效。
