Souto Eliana B, Souto Selma B, Zielinska Aleksandra, Durazzo Alessandra, Lucarini Massimo, Santini Antonello, Horbańczuk Olaf K, Atanasov Atanas G, Marques Conrado, Andrade Luciana N, Silva Amélia M, Severino Patricia
Department of Pharmaceutical Technology, Faculty of Pharmacy (FFUC), University of Coimbra, Pólo das Ciências da Saúde, Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal.
CEB-Centre of Biological Engineering, University of Minho, Campus de Gualtar 4710-057 Braga, Portugal.
Pharmaceutics. 2020 Feb 16;12(2):161. doi: 10.3390/pharmaceutics12020161.
We have developed a new cationic solid lipid nanoparticle (SLN) formulation, composed of Compritol ATO 888, poloxamer 188 and cetyltrimethylammonium bromide (CTAB), to load perillaldehyde 1,2-epoxide, and surface-tailored with a monoclonal antibody for site-specific targeting of human epithelial growth receptor 2 (HER2). Perillaldehyde 1,2-epoxide-loaded cationic SLN (c-SLN), with a mean particle size (z-Ave) of 275.31 ± 4.78 nm and polydispersity index (PI) of 0.303 ± 0.081, were produced by high shear homogenization. An encapsulation efficiency of c-SLN above 80% was achieved. The release of perillaldehyde 1,2-epoxide from cationic SLN followed the Korsemeyer-Peppas kinetic model, which is typically seen in nanoparticle formulations. The lipid peroxidation of c-SLN was assessed by the capacity to produce thiobarbituric acid-reactive substances, while the antioxidant activity was determined by the capacity to scavenge the stable radical DPPH. The surface functionalization of c-SLN with the antibody was done via streptavidin-biotin interaction, monitoring z-Ave, PI and ZP of the obtained assembly (c-SLN-), as well as its stability in phosphate buffer. The effect of plain cationic SLN (c-SLN, monoterpene free), c-SLN and c-SLN- onto the MCF-7 cell lines was evaluated in a concentration range from 0.01 to 0.1 mg/mL, confirming that streptavidin adsorption onto c-SLN- improved the cell viability in comparison to the cationic c-SLN.
我们开发了一种新型阳离子固体脂质纳米粒(SLN)制剂,其由Compritol ATO 888、泊洛沙姆188和十六烷基三甲基溴化铵(CTAB)组成,用于负载紫苏醛1,2 - 环氧化物,并通过单克隆抗体进行表面修饰,以实现对人表皮生长因子受体2(HER2)的位点特异性靶向。通过高剪切均质法制备了负载紫苏醛1,2 - 环氧化物的阳离子SLN(c - SLN),其平均粒径(z - Ave)为275.31±4.78 nm,多分散指数(PI)为0.303±0.081。c - SLN的包封率达到80%以上。阳离子SLN中紫苏醛1,2 - 环氧化物的释放遵循Korsemeyer - Peppas动力学模型,这在纳米粒制剂中较为常见。通过产生硫代巴比妥酸反应性物质的能力评估c - SLN的脂质过氧化,同时通过清除稳定自由基DPPH的能力测定其抗氧化活性。通过链霉亲和素 - 生物素相互作用对c - SLN进行抗体表面功能化,监测所得组装体(c - SLN - )的z - Ave、PI和ZP,以及其在磷酸盐缓冲液中的稳定性。在0.01至0.1 mg/mL的浓度范围内评估了普通阳离子SLN(c - SLN,不含单萜)、c - SLN和c - SLN - 对MCF - 7细胞系的影响,证实与阳离子c - SLN相比,链霉亲和素吸附到c - SLN - 上可提高细胞活力。