Şenel Behiye, Başaran Ebru, Akyıl Evrim, Güven Umay Merve, Büyükköroğlu Gülay
Faculty of Pharmacy, Department of Pharmaceutical Biotechnology, Anadolu University, 26470 Eskisehir, Türkiye.
Faculty of Pharmacy, Department of Pharmaceutical Technology, Anadolu University, 26470 Eskisehir, Türkiye.
ACS Omega. 2024 Feb 27;9(10):11671-11685. doi: 10.1021/acsomega.3c09098. eCollection 2024 Mar 12.
The present study aims to develop a delivery system that can carry small interference RNA (siRNA) with small-molecule chemotherapeutic drugs, which can be used in cancer treatment. The drug delivery system combines the advantages of a therapeutic agent with two different mechanisms to ensure that it is used efficiently for cancer therapy. In this study, a nanostructured lipid carrier system was prepared, Docetaxel was loaded to these systems, and the Eph siRNA was adsorbed to the outer surface. In addition, DOTAP was added to the lipophilic phase to load a positive charge on the lipidic structure for interaction with the cells. Moreover, characterization, cytotoxicity, and transfection procedures were performed on the whole system. This candidate system was also compared to Taxotere, which is the first approved Docetaxel-containing drug on the market. Given the results, it was determined that the particle size of NLC-DTX was 165.3 ± 3.5 nm, the ζ potential value was 38.2 ± 1.7 mV, and the PDI was 0.187 ± 0.024. Entrapment efficacy of nanoparticles was found to be 92.89 ± 0.21%. It was determined that the lipidic system prepared release analyses were able to provide sustained release and exhibit cytotoxicity, even at doses lower than the dose used for Taxotere. The formulations prepared had a higher level of effect on cells when compared with pure DTX and Taxotere, but they also exhibited time-dependent cytotoxicity. It was also observed that the use of Eph siRNA together with the chemotherapeutic agent formulation also contributed to this cell death. The results of the present study indicate that there is a promising carrier system in order to deliver hydrophilic nucleic acids, such as siRNA, together with lipophilic drugs in cancer treatment.
本研究旨在开发一种能够携带小分子化疗药物和小干扰RNA（siRNA）的递送系统，该系统可用于癌症治疗。该药物递送系统结合了具有两种不同作用机制的治疗剂的优点，以确保其能有效地用于癌症治疗。在本研究中，制备了一种纳米结构脂质载体系统，将多西他赛负载到这些系统中，并将Eph siRNA吸附到外表面。此外，将DOTAP添加到亲脂相中，以使脂质结构带上正电荷，以便与细胞相互作用。此外，还对整个系统进行了表征、细胞毒性和转染程序研究。该候选系统还与泰索帝（Taxotere）进行了比较，泰索帝是市场上首个获批的含多西他赛药物。根据结果，确定NLC-DTX的粒径为165.3±3.5nm，ζ电位值为38.2±1.7mV，多分散指数（PDI）为0.187±0.024。发现纳米颗粒的包封率为92.89±0.21%。确定所制备的脂质系统的释放分析能够实现持续释放，并且即使在低于泰索帝所用剂量的情况下也表现出细胞毒性。与纯多西他赛和泰索帝相比，所制备的制剂对细胞具有更高水平的作用，但它们也表现出时间依赖性细胞毒性。还观察到，Eph siRNA与化疗药物制剂一起使用也促成了这种细胞死亡。本研究结果表明，在癌症治疗中，存在一种有前景的载体系统，可用于递送亲水性核酸（如siRNA）以及亲脂性药物。
