Cao Jiafu, Choi Jin-Seok, Oshi Murtada A, Lee Juho, Hasan Nurhasni, Kim Jihyun, Yoo Jin-Wook
College of Pharmacy, Pusan National University, Busan 46241, South Korea.
Department of Medical Management, Chodang University, Muan-gun 58530, South Korea.
Asian J Pharm Sci. 2019 Jan;14(1):86-94. doi: 10.1016/j.ajps.2018.08.008. Epub 2018 Sep 24.
Particle shape has been recognized as one of the key properties of nanoparticles in biomedical applications including targeted drug delivery. Targeting ability of shape-engineered particles depends largely on targeting ligands conjugated on the particle surface. However, poor capacity for surface ligand conjugation remains a problem in anisotropic nanoparticles made with biodegradable polymers such as PLGA. In this study, we prepared anisotropic PLGA nanoparticles with abundant conjugatable surface functional groups by a film stretching-based fabrication method with poly (ethylene-alt-maleic acid) (PEMA). Scanning electron microscopy images showed that microrods and nanorods were successfully fabricated by the PEMA-based film stretching method. The presence of surface carboxylic acid groups was confirmed by confocal microscopy and zeta potential measurements. Using the improved film-stretching method, the amount of protein conjugated to the surface of nanorods was increased three-fold. Transferrin-conjugated, nanorods fabricated by the improved method exhibited higher binding and internalization than unmodified counterparts. Therefore, the PEMA-based film-stretching system presented in this study would be a promising fabrication method for non-spherical biodegradable polymeric micro- and nanoparticles with high capacity of surface modifications for enhanced targeted delivery.
颗粒形状已被公认为纳米颗粒在包括靶向药物递送在内的生物医学应用中的关键特性之一。形状工程化颗粒的靶向能力在很大程度上取决于共轭在颗粒表面的靶向配体。然而，对于由可生物降解聚合物（如聚乳酸-羟基乙酸共聚物，PLGA）制成的各向异性纳米颗粒而言，其表面配体共轭能力较差仍是一个问题。在本研究中，我们通过基于薄膜拉伸的制备方法，使用聚（乙烯-alt-马来酸）（PEMA）制备了具有丰富可共轭表面官能团的各向异性PLGA纳米颗粒。扫描电子显微镜图像显示，通过基于PEMA的薄膜拉伸方法成功制备了微棒和纳米棒。通过共聚焦显微镜和zeta电位测量证实了表面羧酸基团的存在。使用改进的薄膜拉伸方法，共轭到纳米棒表面的蛋白量增加了两倍。通过改进方法制备的转铁蛋白共轭纳米棒比未修饰的纳米棒表现出更高的结合和内化能力。因此，本研究中提出的基于PEMA的薄膜拉伸系统将是一种很有前景的制备方法，用于制备具有高表面修饰能力的非球形可生物降解聚合物微米和纳米颗粒，以增强靶向递送。
