Department of Pharmacy - Pharmaceutical Sciences, University of Bari "Aldo Moro", Orabona St. 4, 70125 Bari, Italy; Drug Research Program, Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, FI-00014 Helsinki, Finland.
Drug Research Program, Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, FI-00014 Helsinki, Finland.
Int J Pharm. 2021 Dec 15;610:121246. doi: 10.1016/j.ijpharm.2021.121246. Epub 2021 Oct 28.
Solid lipid nanoparticles (SLNs) can combine the advantages of different colloidal carriers and prevent some of their disadvantages. The production of nanoparticles by means of microfluidics represents a successful platform for industrial scale-up of nanoparticle manufacture in a reproducible way. The realisation of a microfluidic technique to obtain SLNs in a continuous and reproducible manner encouraged us to create surface functionalised SLNs for targeted drug release using the same procedure. A tumor homing peptide, iRGD, owning a cryptic C-end Rule (CendR) motif is responsible for neuropilin-1 (NRP-1) binding and for triggering extravasation and tumor penetration of the peptide. In this study, the Paclitaxel loaded-SLNs produced by microfluidics were functionalized with the iRGD peptide. The SLNs proved to be stable in aqueous medium andwere characterized by a Z-average under 150 nm, a polydispersity index below 0.2, a zeta-potential between -20 and -35 mV and a drug encapsulation efficiency around 40%. Moreover, in vitro cytotoxic effects and cellular uptake have been assessed using 2D and 3D tumour models of U87 glioblastoma cell lines. Overall, these results demonstrate that the surface functionalization of SLNs with iRGD allow better cellular uptake and cytotoxicity ability.
固体脂质纳米粒（SLNs）可以结合不同胶体载体的优点，并避免它们的一些缺点。通过微流控技术生产纳米粒是一种成功的平台，可以以可重复的方式将纳米粒制造工业规模扩大。我们利用微流控技术连续、可重复地制备固体脂质纳米粒，这一技术的实现激励我们使用相同的方法来制备表面功能化的固体脂质纳米粒，以实现靶向药物释放。iRGD 是一种具有隐蔽 C 端规则（CendR）基序的肿瘤归巢肽，负责与神经纤毛蛋白-1（NRP-1）结合，并触发肽的血管外渗和肿瘤穿透。在本研究中，通过微流控技术制备的载紫杉醇固体脂质纳米粒用 iRGD 肽进行了功能化。SLNs 在水介质中稳定，Z 均粒径小于 150nm，多分散指数低于 0.2，zeta 电位在-20 至-35mV 之间，药物包封效率约为 40%。此外，还使用 U87 神经胶质瘤细胞系的 2D 和 3D 肿瘤模型评估了体外细胞毒性作用和细胞摄取。总的来说，这些结果表明，用 iRGD 对 SLNs 进行表面功能化可以提高细胞摄取和细胞毒性能力。
