摘要
目的 Box-Behnken设计-效应面法优化白屈菜红碱单甲氧基聚乙二醇-聚乳酸羟基乙酸共聚物(methoxy poly(ethylene glycol)-poly(lactic-co-glycolic acid,m PEG-PLGA))纳米粒[chelerythrine mPEG-PLGA nanoparticles,Che@m PEG-PLGA/NPs]处方,并对最佳处方进行体外评价及体内药动学研究。方法 纳米沉淀法制备Che@m PEG-PLGA/NPs,以包封率、载药量和粒径为指标,采用单因素试验结合Box-Behnken设计-效应面法筛选Che@m PEG-PLGA/NPs的最佳处方。将Che@mPEGPLGA/NPs混悬液进一步制备成冻干粉,并考察冻干粉的稳定性和体外释药行为。SD大鼠分为Che原料药组、物理混合物组和Che@m PEG-PLGA/NPs组,分别按20 mg/kg剂量ig后采血,HPLC法测定血药浓度,计算主要药动学参数及相对生物利用度。结果 Che@m PEG-PLGA/NPs最佳处方为mPEG-PLGA用量572 mg、水相与有机相的体积比为2.3∶1、泊洛沙姆188用量为1.2%。Che@m PEG-PLGA/NPs的包封率为(83.49±1.59)%,载药量为(4.61±0.14)%,粒径为(163.93±8.02)nm。Che@m PEG-PLGA/NPs在不同pH值释药介质中的体外释药具有明显的缓释特征。药动学结果显示,Che@mPEGPLGA/NPs的达峰时间(t_(max))延后至(2.12±0.46)h,半衰期(t_(1/2))延长至(5.66±0.93)h,达峰浓度(C_(max))增加至4.49倍,相对口服吸收生物利用度提高至4.66倍。结论 Che@m PEG-PLGA/NPs可显著提高Che的口服吸收生物利用度,值得进一步研究。
Objective Box-Behnken design-response surface method was employed to optimize the formulation of chelerythrine methoxy poly(ethylene glycol)-poly(lactic-co-glycolic acid(mPEG-PLGA) nanoparticles(Che@mPEG-PLGA/NPs),and carry out in vitro evaluation and oral pharmacokinetics study of optimal prescriptions.Methods Nano-precipitation method was employed to prepare Che@mPEG-PLGA/NPs.Encapsulation rate,drug loading and particle size were used as evaluation indexes,single factor investigation method combined with Box-Behnken response surface design method was combined to investigate the optimal prescriptions of Che@mPEG-PLGA/NPs,and then its lyophilized powder was prepared.Stability and release behavior in vitro of lyophilized powder was investigated.SD rats were divided into Che suspension,physical mixture and Che@mPEG-PLGA/NPs groups,blood samples were collected after gastric administration at a dose of 20 mg/kg.The plasma concentrations were determined by HPLC,main pharmacokinetic parameters and relative bioavailability were calculated.Results The optimal formulation of Che@ mPEGPLGA/NPs:mPEG-PLGA dosage was 572 mg,water phase to organic phase volume ratio was 2.3∶1 and concentration of poloxamer 188 was 1.2%.Envelopment efficiency,drug loading and particle size of Che@mPEG-PLGA/NPs were(83.49 ± 1.59)%,(4.61 ±0.14)% and(163.93 ± 8.02) nm.Drug release in vitro had obvious sustained-release characteristics in different pH dissolution media.Pharmacokinetic results showed that tmax of Che@mPEG-PLGA/NPs was delayed to(2.12 ± 0.46) h,t1/2was prolonged to(5.66 ± 0.93)h,Cmax was increased to 4.49 times and relative oral bioavailability was enhanced to 4.66 times.Conclusion Che@mPEG-PLGA/NPs can significantly improve the oral bioavailability of Che,which was worthy of further study.
作者
刘万路
LIU Wan-lu(Weihai Ocean Vocational College,Weihai 264300,China)
出处
《中草药》
CAS
CSCD
北大核心
2022年第23期7361-7371,共11页
Chinese Traditional and Herbal Drugs
基金
国家自然科学青年基金资助项目(51804021)。
