木犀草素纳米结构脂质载体的制备、优化及抗菌活性

刘媛媛; 贺朝

doi:10.11665/j.issn.1000-5048.20200606

木犀草素纳米结构脂质载体的制备、优化及抗菌活性

刘媛媛¹,
贺朝²

1.
咸阳职业技术学院,咸阳 712000
2.
陕西中医药大学,咸阳 712046

基金项目: 陕西省自然科学基础研究计划项目（No.2019JQ-871）

计量
- 文章访问数: 241
- HTML全文浏览量: 19
- PDF下载量: 607
出版历程
- 收稿日期: 2020-06-28
- 修回日期: 2020-10-14
- 刊出日期: 2020-12-24

Preparation，optimization and antibacterial activity of luteolin nanostructured lipid carriers

LIU Yuanyuan¹,
HE Chao²

Funds: This study was supported by the Natural Science Basic Research Program of Shaanxi Province (No.2019JQ-871)

摘要

摘要: 制备和优化木犀草素纳米结构脂质载体（Lut-NLCs），并考察其体外抗菌活性。采用热熔乳化-超声波制备Lut-NLCs，以固体脂质质量浓度（X₁）、液体脂质质量浓度（X₂）、表面活性剂质量浓度（X₃）作为自变量，以粒径大小（Y₁）和包封率（Y₂）作为因变量，利用Box-Behnken实验设计优化得到Lut-NLCs最佳处方，通过透射电镜观察Lut-NLCs的微观结构；并考察了Lut-NLCs的体外释药特性，比较了木犀草素原料药和Lut-NLCs的体外抗菌活性。经实验优化得到Lut-NLCs的最佳处方组成为：固体脂质质量浓度为18.0 mg/mL，液体脂质质量浓度为13.0 mg/mL，表面活性剂质量浓度为15.0 mg/mL；制备3批Lut-NLCs的平均粒径为（210.4±17.3）nm，包封率为（88.4±1.2）%；在透射电镜可观察到Lut-NLCs为类球状，表面光滑，粒径分布均匀；体外释放结果显示，Lut-NLCs在前期药物释放较快，后期药物释放较为平稳，12 h药物释放可以达到95%；抗菌圈实验结果显示，Lut-NLCs对金黄色葡萄球菌、大肠埃希菌的抑菌效果均高于木犀草素原料药。本研究制备的木犀草素纳米结构脂质载体处方设计合理，制备工艺简单，体外抗菌活性显著，有望成为木犀草素外用给药的一种有效途径。
- 木犀草素 /
- 纳米结构脂质载体 /
- 热熔乳化-超声波 /
- 抗菌活性
Abstract: To prepare and optimize luteolin nanostructured lipid carriers (Lut-NLCs) and investigate their antibacterial activity in vitro. Lut-NLCs were prepared by hot melt emulsification-ultrasonic method. The solid lipid concentration (X₁),liquid lipid concentration (X₂) and surfactant concentration (X₃) were used as independent variables,with the average particle size (Y₁) and the encapsulation efficiency (Y₂) as the dependent variables. The optimal formulation of Lut-NLCs was obtained through Box-Behnken experiment design. The microstructure of Lut-NLCs was observed by transmission electron microscopy(TEM). The in vitro release characteristics of Lut-NLCs were investigated. Furthermore, the in vitro antibacterial activities of luteolin and Lut-NLCs were compared. The formulation composition of Lut-NLCs was optimized as follows:the concentration of the solid lipid, liquid lipid and surfactant were 13.0 mg/mL,15.0 mg/mL,and 15.0 mg/mL,respectively. Three batches of Lut-NLCs were prepared with an average particle size of (210.4±17.3) nm,and an encapsulation efficiency of (88.4±1.2)%. Lut-NLCs were observed to be spheroidal,with a smooth surface and a uniform particle size distribution by TEM. The drug release profiles of Lut-NLCs showed a bursting release in the early stage and a slow and stable release in the later stage. Moreover, the cumulative release amount of drug reached 95% in 12 hours. The results of antibacterial circle experiment showed that the antibacterial effect of Lut-NLCs on Staphylococcus aureus and Escherichia coli was higher than that of luteolin raw materials. In this study,the formulation of Lut-NLCs prepared by simple preparation process is reasonable,and Lut-NLCs also exhibited the significant in vitro antibacterial activity. It is expected to be an effective way for external application of luteolin.
- luteolin /
- nanostructured lipid carriers /
- hot melt emulsification-ultrasonic method /
- antibacterial activity

HTML全文

参考文献(17)

[1]	. J Pharm Res （药学研究），2019，38（2）：108?111，119.
[2]	Fan WH，Huang M. Effects of luteolin on airway remodeling in asthmatic mice［J］. Anhui Med Pharm J （安徽医药），2006，10（9）：647?649.
[3]	Shi XX，Quan WJ，Tang Q，et al. Research progress of molecular mechanismsof luteolin against breast［J］. Anti-Tumor Pharmacy （肿瘤药学），2018，8（2）：135?138.
[4]	Huang CC，Gao X，Sun TT，et al. The antimicrobial activity of luteolin against four bacteria in vitro［J］. Chin J Veterinary Sci （中国兽医学报），2017，37（8）：1558?1561.
[5]	Qian W，Mingjie X. Antibacterial activity and mechanism of luteolin on Staphylococcus aureus［J］. Acta Microbiol Sin （微生物学报），2010，50（9）：1180?1184.
[6]	Wang M，Zhang M，Zhang FN，et al. Construction，optimization and antitumor activity of luteolin-loaded mPEG-PLGA nanoparticles［J］. J Logistics Univ CAPF（武警后勤学院学报医学版），2018，27（11）：900?905，910.
[7]	Zhao HR，Zhao Y. Study on effect of O/W microemulsion in enhancing solubility of luteolin［J］. Applied Chem Indus （应用化工），2014，43（6）：1054?1056，1077.
[8]	Hu Y，Chen X，Li Z，et al. Thermosensitive in situ gel containing luteolin micelles is a promising efficient agent for colorectal cancer peritoneal metastasis treatment［J］. J Biomed Nanotechnol，2020，16（1）：54?64.
[9]	Li ML，Li XL，Yu DC，et al. Preparation of β-cyclodextrin inclusion compound of luteolin［J］. Chin J New Drugs （中国新药杂志），2004，13（6）：524?526.
[10]	Khan J，Alexander A，Ajazuddin，et al. Luteolin-phospholipid complex：preparation，characterization and biological evaluation［J］. J Pharm Pharmacol，2014，66（10）：1451?1462.
[11]	Cortesi R，Valacchi G，Muresan XM，et al. Nanostructured lipid carriers （NLC） for the delivery of natural molecules with antimicrobial activity：production，characterisation and in vitro studies［J］. J Microencapsul，2017，34（1）：63?72.
[12]	Lin CH，Fang YP，Al-Suwayeh SA，et al. Percutaneous absorption and antibacterial activities of lipid nanocarriers loaded with dual drugs for acne treatment［J］. Biol Pharm Bull，2013，36（2）：276?286.
[13]	Liu YY. Optimization of harmine-loaded nanostructure lipid carriers by Box-Behnken design and its anticancer effect study［J］. West China J Pharm Sci （华西药学杂志），2019，34（4）：337?342.
[14]	Zhang XJ，Zuo GY，Wang T，et al. In vitro study on synergetic anti-MRSA effects of luteolin combined with antibacterial drugs［J］. Prog in Pharm Sci （药学进展），2012，36（4）：173?179.
[15]	Cao FL，Guo CY，Li QL，et al. Research progress on the preparation and application of nanostructured lipid carriers［J］. Chin J Biochem Pharm （中国生化药物杂志），2012，33（1）：93?96.
[16]	Li ZH，Sun LJ，Wang YL，et al. Preparation and antibacterial activity of stable carboxymethyl chitosan nanoparticles suspension with antibacterial lipopeptide［J］. J Microbiol （微生物学杂志），2013，33（1）：4?7.
[17]	Hong W，Liu LP，Zhao YN，et al. Pluronic-based nano-self-assemblies of bacitracin A with a new mechanism of action for an efficient in vivo therapeutic effect against bacterial peritonitis［J］. J Nanobiotechnol，2018，16：66.