药学学报, 2019, 54(8): 1509-1514
引用本文:
孙钲, 许焕, 卫一丹, 张欣, 毛世瑞. 表面疏水性可调控型载药聚合物-脂质纳米粒的制备与表征[J]. 药学学报, 2019, 54(8): 1509-1514.
SUN Zheng, XU Huan, WEI Yi-dan, ZHANG Xin, MAO Shi-rui. Preparation and characterization of drug-loaded polymer-lipid hybrid nanoparticles with tunable surface hydrophobicity[J]. Acta Pharmaceutica Sinica, 2019, 54(8): 1509-1514.

表面疏水性可调控型载药聚合物-脂质纳米粒的制备与表征
孙钲, 许焕, 卫一丹, 张欣, 毛世瑞
沈阳药科大学药学院, 辽宁 沈阳 110016
摘要:
纳米粒表面疏水性对药物递送有显著的影响。本研究旨在探究采用自组装法制备表面疏水性可调控型载药纳米粒的可行性。以帕比司他(panobinostat,PNB)为模型药物,Soluplus为载体制备聚合物载药胶束,使用3种单甘油酯,即单油酸甘油酯(glycerly monooleate,GMO)、亚油酸甘油酯(glycerly linoleate,GML)和亚麻酸甘油酯(glycerly linolenate,GMLO)对胶束进行表面改性,得到聚合物-脂质纳米粒,采用玫瑰红法和黏附素法表征改性后得到的纳米粒表面疏水性,考察单甘油酯种类及用量对载药纳米粒的物理化学性质及疏水性的影响。结果表明,单一Soluplus载药胶束的粒径77.97±0.78 nm、zeta电位0.44±0.29 mV、包封率99.45%±1.47%、玫瑰红结合常数(K)值0.008±0.002,与黏附素亚粒子共孵育后粒径增幅(I) 7.90±1.41nm,经GMO、GML和GMLO(用量为Soluplus的1%)改性后得到的聚合物-脂质纳米粒表面疏水性均显著增强,K值分别为0.055±0.010、0.050±0.011和0.058±0.008;I值分别为17.37±4.48、22.60±2.10和25.13±3.89 nm。但经GMLO改性后纳米粒的理化性质(粒径81.60±4.52 nm、zeta电位0.77±0.03 mV和包封率99.59%±0.20%)无显著变化。因此,选择GMLO进一步考察其用量为Soluplus的1%~3%时对纳米粒的性质影响,结果表明,GMLO用量对纳米粒的粒径、zeta电位、包封率及体外释放行为均无显著变化,但粒子表面疏水性随GMLO用量增加呈线性增强。本研究表明,自组装法可制备基于Soluplus和GMLO的聚合物-脂质纳米粒,通过改变GMLO与Soluplus用量比可实现对表面疏水性的调控,用于开展纳米粒表面亲疏水性对体系递送过程影响的基础规律探究。
关键词:    纳米粒      聚乙烯己内酰胺-聚乙酸乙烯酯-聚乙二醇接枝共聚物      帕比司他      表面疏水性      黏附素     
Preparation and characterization of drug-loaded polymer-lipid hybrid nanoparticles with tunable surface hydrophobicity
SUN Zheng, XU Huan, WEI Yi-dan, ZHANG Xin, MAO Shi-rui
School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China
Abstract:
The surface hydrophobicity of nanoparticles plays an important role in drug delivery process. The aim of this study was to verify the feasibility of using self-assembly method to prepare drug-loaded nanoparticles with tunable surface hydrophobicity. Here, Soluplus was selected as the polymeric carrier to prepare panobinostat (PNB) loaded micelles. Three different monoglycerides, glycerly monooleate (GMO), glycerly linoleate (GML) and glycerly linolenate (GMLO), were used to modify the surface of PNB-Soluplus micelles to prepare polymerlipid hybrid nanoparticles (PLHNs). The effect of monoglyceride type and amount on the physico-chemical properties of PNB-loaded PLHNs was investigated, and the surface hydrophobicity of PLHNs was characterized by Rose Bengal (RB) binding method and mucin particle method. The results suggested that compared with the PNB-Soluplus micelles (particle size 77.97±0.78 nm, zeta potential 0.44±0.29 mV, entrapment efficiency 99.45%±1.47%, the RB binding constant (K) value 0.008±0.002, the increased particle size after mixing with mucin particles 7.90±1.41 nm), surface hydrophobicity of the PLHNs increased significantly when modified by GMO, GML, GMLO, with K values of 0.055±0.010, 0.050±0.011 and 0.058±0.008, respectively. The increased particle sizes after mixing with mucin particles were 17.37±4.48 nm, 22.60±2.10 nm and 25.13±3.89 nm, respectively. Among them, the physico-chemical properties of the GMLO modified PNB-loaded PLHNs (particle size 81.60±4.52 nm, zeta potential 0.77±0.03 mV, entrapment efficiency 99.59%±0.20%) kept constant, thus GMLO was selected to further investigate the effect of GMLO mass ratio (1%-3%) to Soluplus on the properties of the nanoparticles. While no statistical significant difference in particle size, zeta potential, entrapment efficiency or in vitro release behavior was found when GMLO ratio increased, the surface lipophilicity of the PLHNs, as characterized by K values and the increased particle sizes after mixing with mucin particles, increased almost linearly with the increase of GMLO amount. In conclusion, we demonstrated that drug-loaded PLHNs based on Soluplus and GMLO can be prepared by self-assembly method, and the surface hydrophobicity was tunable by modifying the mass ratio of GMLO to Soluplus. This approach could be used for related basic science research aiming to elucidate the effect of surface hydrophobicity on in vivo behavior of drug-loaded system.
Key words:    nanoparticle    polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer    panobinostat    surface hydrophobicity    mucins   
收稿日期: 2019-05-27
DOI: 10.16438/j.0513-4870.2019-0417
基金项目: 国家自然科学基金资助项目(31870987).
通讯作者: 毛世瑞,Tel:86-24-23986358,E-mail:maoshirui@syphu.edu.cn
Email: maoshirui@syphu.edu.cn
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