摘要
结合前期制备的水飞蓟宾过饱和自纳米微乳,考察醋酸羟丙甲纤维素琥珀酸酯对过饱和自纳米乳中水飞蓟宾吸收的影响。通过MTT法评价自乳化制剂的毒性,通过建立Caco-2细胞单层模型评价自乳化制剂的体外膜透性和促吸收作用;大鼠灌胃自乳化制剂后,通过测定水飞蓟宾血药浓度评价体内外过饱和相关性。MTT结果表明制剂质量浓度低于2 mg·mL^(-1)(C_(SLB)约100μg·mL^(-1))对细胞无毒性;加入聚合物对细胞的存活率无明显影响。转运结果显示,与溶液组相比,自乳化制剂组的P_(app)(AP→BL)均具有极显著增加;在0~30 min聚合物可降低水飞蓟宾的转运速率;但在2 h内水飞蓟宾过饱和自纳米乳与水飞蓟宾自纳米乳未表现出过饱和转运差异。药动学参数显示,与水飞蓟宾混悬液比较,水飞蓟宾自纳米乳和水飞蓟宾过饱和自纳米乳组血药浓度均有显著的提高,C_(max)分别为其5.25,9.69倍;相对生物利用度分别为其578.45%,1139.44%;另外,水飞蓟宾过饱和自纳米乳的C_(max)和相对生物利用度分别为水飞蓟宾自纳米乳的1.85倍和197%。因此过饱和自纳米乳体系一方面可通过维持水飞蓟宾过饱和稳定性,增加水飞蓟宾胃肠道溶解度;另一方面通过其制剂组成调控水飞蓟宾渗透转运过程,两者共同促进水飞蓟宾转运吸收,进而提高水飞蓟宾的口服生物利用度。
To evaluate the effects of Hydroxypropyl methylcellulose acetate succinate(HPMCAS MF)on absorption of silybin(SLB)from supersaturable self-nanoemulsifying drug delivery system which was pre-prepared at the early stage experiment.The cell toxicity of self-emulsifying preparation was evaluated by the MTT method,and the in vitro membrane permeability and absorption promoting effect of the self-emulsifying preparation were evaluated by establishing a Caco-2 cell monolayer model.The in vivo and in vitro supersaturation correlation was evaluated via the blood concentration of SLB.The results of MTT showed that the concentration of the preparation below 2 mg·mL^(-1)(C_(SLB)100μg·mL^(-1))was not toxic to Caco-2 cells,and the addition of polymer had no significant effect on Caco-2 cells viability.As compared with the solution group,the transport results showed that the P_(app)(AP→BL)of the self-emulsifying preparation had a very significant increase;the transport rate of silybin can be reduced by polymer in 0-30 min;however,there was no difference in supersaturated transport between supersaturated SLB self-nanoemulsion drug delivery system(SLB-SSNEDDS)and SLB self-nanoemulsion drug delivery system(SLB-SNEDDS)within 2 hours.As compared with SLB suspension,pharmacokinetic parameters showed that the blood concentration of both SLB-SNEDDS and SLB-SSNEDDS groups were significantly increased,and C_(max)was 5.25 times and 9.69 times respectively of that in SLB suspension group,with a relative bioavailability of 578.45%and 1139.44%respectively.C_(max)and relative bioavailability of SLB-SSNEDDS were 1.85 times and 197%of those of SLB-SNEDDS,respectively.Therefore,on the one hand,SSNEDDS can increase the solubility of SLB in gastrointestinal tract by maintaining stability of SLB supersaturation state;on the other hand,the osmotic transport process of SLB was regulated through the composition of its preparations,and both of them could jointly promote the transport and absorption of SLB to improve the oral bioavailability of SLB
作者
赖章婷
丁海波
蒋且英
袁其里
廖正根
LAI Zhang-ting;DING Hai-bo;JIANG Qie-ying;YUAN Qi-li;LIAO Zheng-gen(Key Laboratory of Modern Preparation of Traditional Chinese Medicine,Ministry of Education,Jiangxi University of Traditional Chinese Medicine,Nanchang 330004,China;Experimental Animal Center of Traditional Chinese Medicine,Jiangxi University of Traditional Chinese Medicine,Nanchang 330004,China;Medical Device Testing Center of Jiangxi Provinice,Nanchang 330029,China)
出处
《中国中药杂志》
CAS
CSCD
北大核心
2021年第5期1120-1127,共8页
China Journal of Chinese Materia Medica
基金
江西省一流学科项目(JXSYLXK-ZHYAO059)。
关键词
水飞蓟宾
过饱和自纳米乳
Caco-2细胞转运
药代动力学
吸收
silybin
supersaturable self-nanoemulsifying drug delivery system
Caco-2 cell transport
pharmacokinetics
absorption
