Chountoulesi Maria, Pippa Natassa, Chrysostomou Varvara, Pispas Stergios, Chrysina Evangelia D, Forys Aleksander, Otulakowski Lukasz, Trzebicka Barbara, Demetzos Costas
Section of Pharmaceutical Technology, Department of Pharmacy, School of Health Sciences, National and Kapodistrian University of Athens, Panepistimioupolis Zografou, 15771 Athens, Greece.
Theoretical and Physical Chemistry Institute, National Hellenic Research Foundation, 48 Vassileos Constantinou Avenue, 11635 Athens, Greece.
Polymers (Basel). 2019 Aug 26;11(9):1400. doi: 10.3390/polym11091400.
There is an emerging need to evolve the conventional lyotropic liquid crystalline nanoparticles to advanced stimuli-responsive, therapeutic nanosystems with upgraded functionality. Towards this effort, typically used stabilizers, such as Pluronics, can be combined or replaced by smart, stimuli-responsive block copolymers. The aim of this study is to incorporate the stimuli-responsive amphiphilic block copolymer poly(2-(dimethylamino)ethyl methacrylate)-b-poly(lauryl methacrylate) (PDMAEMA-b-PLMA) as a stabilizer in lipidic liquid crystalline nanoparticles, in order to provide steric stabilization and simultaneous stimuli-responsiveness. The physicochemical and morphological characteristics of the prepared nanosystems were investigated by light scattering techniques, cryogenic-transmission electron microscopy (cryo-TEM), X-ray diffraction (XRD) and fluorescence spectroscopy. The PDMAEMA-b-PLMA, either individually or combined with Poloxamer 407, exhibited different modes of stabilization depending on the lipid used. Due to the protonation ability of PDMAEMA blocks in acidic pH, the nanoparticles exhibited high positive charge, as well as pH-responsive charge conversion, which can be exploited towards pharmaceutical applications. The ionic strength, temperature and serum proteins influenced the physicochemical behavior of the nanoparticles, while the polymer concentration differentiated their morphology; their micropolarity and microfluidity were also evaluated. The proposed liquid crystalline nanosystems can be considered as novel and attractive pH-responsive drug and gene delivery nanocarriers due to their polycationic content.
将传统的溶致液晶纳米颗粒发展为具有升级功能的先进刺激响应型治疗纳米系统的需求日益凸显。为此,可以将通常使用的稳定剂(如普朗尼克)与智能、刺激响应型嵌段共聚物结合或替代。本研究的目的是将刺激响应型两亲性嵌段共聚物聚(甲基丙烯酸2-(二甲氨基)乙酯)-b-聚(甲基丙烯酸月桂酯)(PDMAEMA-b-PLMA)作为稳定剂掺入脂质液晶纳米颗粒中,以提供空间稳定作用并同时具备刺激响应性。通过光散射技术、低温透射电子显微镜(cryo-TEM)、X射线衍射(XRD)和荧光光谱对所制备纳米系统的物理化学和形态特征进行了研究。PDMAEMA-b-PLMA单独使用或与泊洛沙姆407联合使用时,根据所使用的脂质表现出不同的稳定模式。由于PDMAEMA嵌段在酸性pH下具有质子化能力,纳米颗粒表现出高正电荷以及pH响应性电荷转换,这可用于药物应用。离子强度、温度和血清蛋白影响纳米颗粒的物理化学行为,而聚合物浓度则使它们的形态有所不同;还评估了它们的微极性和微流动性。所提出的液晶纳米系统由于其聚阳离子含量,可被视为新型且有吸引力的pH响应型药物和基因递送纳米载体。