青藤碱磷脂复合物纳米结构脂质载体的制备、表征及药动学研究
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摘要
为制备青藤碱磷脂复合物纳米结构脂质载体,并进行体外和SD大鼠体内评价。实验采用溶剂挥发法制备青藤碱磷脂复合物,乳化超声法制备青藤碱磷脂复合物纳米结构脂质载体。考察其粒径分布、Zeta电位,包封率,载药量及体外释药等基本理化性质。SD大鼠分别灌胃给予青藤碱混悬液和青藤碱磷脂复合物纳米结构脂质载体,比较药动学行为及生物利用度。结果显示,青藤碱磷脂复合物纳米结构脂质载体的平均粒径为201.32±5.05 nm,Zeta电位为-22.2±1.5 mV,包封率为80.31±1.01%,载药量为4.42±0.28%,体外释药具有明显的缓释特征,体外释药模型符合Weibull释药模型,拟合方程为:LnLn(1/1-Mt/M∞)=0.576 6Lnt-1.478 1(r=0.988 8)。体内药动学研究结果表明,磷脂复合物纳米结构脂质载体改变了青藤碱的药动学行为,增强了体内吸收,延长了青藤碱在体内滞留时间,相对生物利用度提高到了1.75倍。因此,青藤碱磷脂复合物纳米结构脂质载体可显著促进青藤碱体内吸收,提高其口服生物利用度。
To prepare sinomenine phospholipids complex nanostructured lipid carriers,and in vitro and in vivo in SD rats were evaluated.Solvent evaporation method was used to prepare sinomenine phospholipids complex,and ultrasonic emulsification method was adopted to prepare its nanostructured lipid carriers.The basic physicochemical properties,including particle size,zeta potential,encapsulation efficiency,drug loading and drug release in vitro were studied.The pharmacokinetics and bioavailability were compared after oral administration of sinomenine and its phospholipids complex nanostructured lipid carriers.The results showed that particle size,zeta potential,encapsulation efficiency and drug loading of sinomenine phospholipids complex nanostructured lipid carriers were 201.32±5.05 nm,-22.2±1.5 mV,80.31±1.01% and 4.42±0.28%,respectively.The drug release in vitro has a characteristic of slow release,which was better agreed with Weibull kinetics model and the equation was LnLn(1/1-Mt/M∞)=0.576 6 Lnt-1.478 1(r=0.988 8).The pharmacokinetic results showed that the pharmacokinetic behavior was changed,the absorption was enhanced,the residence time was extend and the bioavailability of sinomenine was enhanced by 1.75 times.Therefore,sinomenine phospholipids complex nanostructured lipid carriers could promote the drug absorption and enhance the bioavailability significantly.
To prepare sinomenine phospholipids complex nanostructured lipid carriers,and in vitro and in vivo in SD rats were evaluated.Solvent evaporation method was used to prepare sinomenine phospholipids complex,and ultrasonic emulsification method was adopted to prepare its nanostructured lipid carriers.The basic physicochemical properties,including particle size,zeta potential,encapsulation efficiency,drug loading and drug release in vitro were studied.The pharmacokinetics and bioavailability were compared after oral administration of sinomenine and its phospholipids complex nanostructured lipid carriers.The results showed that particle size,zeta potential,encapsulation efficiency and drug loading of sinomenine phospholipids complex nanostructured lipid carriers were 201.32±5.05 nm,-22.2±1.5 mV,80.31±1.01% and 4.42±0.28%,respectively.The drug release in vitro has a characteristic of slow release,which was better agreed with Weibull kinetics model and the equation was LnLn(1/1-Mt/M∞)=0.576 6 Lnt-1.478 1(r=0.988 8).The pharmacokinetic results showed that the pharmacokinetic behavior was changed,the absorption was enhanced,the residence time was extend and the bioavailability of sinomenine was enhanced by 1.75 times.Therefore,sinomenine phospholipids complex nanostructured lipid carriers could promote the drug absorption and enhance the bioavailability significantly.
引文
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2 Zhang XZ,Chen XQ,Pan XG.Preparation of sinomenine-loaded solid lipid nanoparticles[J].Chin Hosp Pharm J(中国医院药学杂志),2008,28:2081-2084.
3 Huo ZJ,Li TT,Li MS,et al.Study on preparation technology of sinomenine long circulating liposomes[J].J Mod Med Health(现代医药卫生),2018,34:12-14.
4 Li X,Liu YT,Wu SM,et al.Transdermal delivery character of sinomenine microemulsion[J].Chin Tradit Pat Med(中成药),2008,30:1119-1122.
5 Wei YG,Xu K.Sinomenine phospholipids complex:preparation,characteration and skin permeation test in vitro[J].Nat Prod Res Dev(天然产物研究与开发),2018,30:1449-1453.
6 Wu XC,Hao HJ,Liu YX,et al.Bioavailability of 10-hydroxycamptothecin-phospholipid complex loaded by solid dispersion and lipid-based formulations[J].J Chin Pharm Sci,2015,24:779-787.
7 Wu XC,Hao HJ,Liu YX,et al.Comparison of bioavailability of two kinds of solid dispersion from 10-hydroxycamptothecin in SD rats in vivo[J].Chin J Chin Mater Med(中国中药杂志),2016,41:1130-1134.
8 Hao HJ,Jia YZ,Han R.Phytosomes:an effective approach to enhance the oral bioavailability of active constitutents extracted from plants[J].J Chin Pharm Sci,2013,22:385-392.
9 Xu K,Wei YG.Lappaconitine phospholipids complex nanoparticles:preparation,characterization and pharmacokinetic[J].Nat Prod Res Dev(天然产物研究与开发),2018,30:870-874.
10 Yuan X,Liu X,Hao WQ,et al.Optimization of penetration enhancer of nabiletin micromulision gel by orthogonal test and evaluation of drug release in vitro[J].Nat Prod Res Dev(天然产物研究与开发),2017,29:851-861.
11 Elmowafy M,Shalaby K,Badran M,et al.Fatty alcohol containing nanostructured lipid carrier(NLC) for progesterone oral delivery:in vitro and ex vivo studies[J].J Drug Deliv Sci Tec,2018,45:230-239.
12 Huang J,Wang Q,Li T,et al.Nanostructured lipid carrier(NLC) as a strategy for encapsulation of quercetin and linseed oil:Preparation and in vitro characterization studies[J].J Food Eng,2017,215(10):1-12.
13 Shi GY,Wang XL,Wang RL,et al.Preparation and in vitro release of artemether nanostructured lipid carriers[J].Chin J Pharm,2017,48:699-705.
14 Babazadeh A,Ghanbarzadeh B,Hamishehkar H.Formulation of food grade nanostructured lipid carrier(NLC) for potential applications in medicinal-functional foods[J].J Drug Deliv Sci Tec,2017,44:50-58.
15 Feng SY,Wang CJ,Ding YP,et al.Preparation of nanostructured lipid carriers for volatile oils from Artemisiae argyi Folium[J].Chin Tradit Pat Med(中成药),2018,40:70-75.
16 Feng F,Wang HC,Yang XC,et al.Optimization of freeze-drying process of furanodiene-loaded nanostructured lipid carriers for injection[J].Chin New Drug J(中国新药杂志),2016,25:1765-1769.