Laboratory of Bioactive Polymers, Institute of Polymers, Bulgarian Academy of Sciences, Acad. G. Bonchev St, Bl. 103A, BG-1113 Sofia, Bulgaria.
Laboratory of Bioactive Polymers, Institute of Polymers, Bulgarian Academy of Sciences, Acad. G. Bonchev St, Bl. 103A, BG-1113 Sofia, Bulgaria.
Int J Pharm. 2020 Jun 30;584:119426. doi: 10.1016/j.ijpharm.2020.119426. Epub 2020 May 21.
Berberine chloride (Brb) is a natural isoquinoline quaternary alkaloid that displayed a set of beneficial biological properties such as antioxidant, antimicrobial, antitumor, anti-inflammatory, and antiviral. Brb is poorly soluble in water and body fluids and its intestinal absorption is very low, which predetermine its low bioavailability. Polymeric nanoparticles seem to be a good platform to overcome these drawbacks. In this study, for the first time, stable aqueous dispersions of nanoparticles (NPs) based on complexes of Brb and poly(methacrylic acid) (PMA) or poly(acrylic acid) (PAA), were successfully prepared by mixing their dilute aqueous solutions as evidenced by the performed dynamic light scattering (DLS) and transmission electron microscopy (TEM) analyses. It was found that the mean diameter and zeta potential of NPs depended on the Brb molar fraction. In the case of Brb/PMA and Brb/PAA NPs the encapsulation efficiency was observed to approach a maximum value of 58.9 ± 0.5% and of 78.4 ± 0.9%, respectively, at values of Brb molar fraction at which maximum amount of complexes was obtained. The performed differential scanning calorimetry (DSC) and X-ray diffraction (XRD) analyses revealed that Brb incorporated in the NPs was in the amorphous state. The Brb release profile was pH-dependent. The Brb-containing NPs displayed good antioxidant capacity close to that of free Brb. In vitro cell viability studies demonstrated that the Brb/PMA (PAA) NPs exerted a higher cytotoxicity against HeLa tumor cell than non-tumor BALB/c 3T3 mouse fibroblast cells. Thus, the obtained NPs are promising candidates in the drug delivery systems in the treatment of cervical tumors.
盐酸小檗碱（Brb）是一种天然异喹啉季铵生物碱，具有抗氧化、抗菌、抗肿瘤、抗炎和抗病毒等一系列有益的生物学特性。Brb 在水中和体液中的溶解度很差，其肠道吸收非常低，这决定了其生物利用度低。聚合物纳米粒子似乎是克服这些缺点的良好平台。在这项研究中，首次通过混合其稀水溶液，成功制备了基于 Brb 与聚（甲基丙烯酸）（PMA）或聚（丙烯酸）（PAA）复合物的纳米粒子（NPs）的稳定水性分散体，这一点通过动态光散射（DLS）和透射电子显微镜（TEM）分析得到了证明。结果发现，NPs 的平均直径和zeta 电位取决于 Brb 的摩尔分数。在 Brb/PMA 和 Brb/PAA NPs 的情况下，观察到包封效率分别在获得最大复合物量时的 Brb 摩尔分数值接近 58.9±0.5%和 78.4±0.9%达到最大值。进行的差示扫描量热法（DSC）和 X 射线衍射（XRD）分析表明，掺入 NPs 中的 Brb 处于无定形状态。Brb 的释放曲线呈 pH 依赖性。含 Brb 的 NPs 表现出与游离 Brb 相近的良好抗氧化能力。体外细胞活力研究表明，与非肿瘤 BALB/c 3T3 小鼠成纤维细胞相比，Brb/PMA（PAA）NPs 对 HeLa 肿瘤细胞具有更高的细胞毒性。因此，所获得的 NPs 是治疗宫颈癌的药物输送系统中的有前途的候选物。
