土木香内酯生物黏附微球的制备及其对溃疡性结肠炎模型大鼠的药效评价  

Preparation of Alantolactone Bioadhesive Microspheres and Its Effects on Ulcerative Colitis Model Rats

作　　者：唐逢雨 仇坤 周利梅 王朔 尉小慧[1,2] TANG Fengyu;QIU Kun;ZHOU Limei;WANG Shuo;WEI Xiaohui(MOE Key Laboratory of Standardization of Chinese Medicine,Institute of Chinese Materia Medica,Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China;Shanghai R&D Center for Standardization of Chinese Medicine,Shanghai 201203,China)

机构地区：[1]上海中医药大学中药研究所,中药标准化教育部重点实验室,上海201203 [2]上海中药标准化研究中心,上海201203

出　　处：《中国药学杂志》2023年第19期1759-1768,共10页Chinese Pharmaceutical Journal

摘　　要：目的 制备土木香内酯(ATL)生物黏附微球,对其进行质量表征、体外释放机制研究以及治疗大鼠溃疡性结肠炎(UC)的药效学评价。方法 采用乳化溶剂挥发法制备ATL生物黏附微球,并对其进行形态、粒径、黏附性、包封率、载药量、X射线衍射(XRD)以及差示扫描量热(DSC)等一系列表征;测定其体外释放度,进行方程拟合,探讨释药机制;以噁唑酮诱导大鼠UC模型,研究ATL生物黏附微球结肠溶胶囊对UC的治疗作用。结果 ATL生物黏附微球扫描电镜下圆整,表面粗糙且存在溶剂挥发后留下的大量微孔;粒径为(205.95±2.72)μm;黏附性为(91.33±2.52)%;包封率为(95.54±0.62)%;载药量为(42.62±0.29)%;XRD和DSC结果表明,ATL大部分以无定型分子状态分散于微球中;体外释放24 h可达89%,为扩散与溶蚀共同作用,以扩散为主;装入结肠溶胶囊给药后,可显著改善UC模型大鼠体重下降、便血、拉稀、结肠缩短、脾脏水肿等症状并缓解UC模型大鼠的结肠病理损伤,显著减少UC模型大鼠中髓过氧化物酶(MPO)和肿瘤坏死因子α(TNF-α)的表达,提高炎性因子白介素-4(IL-4)与白介素-13(IL-13)的表达。结论 制备的ATL生物黏附微球载药量高,将其装入结肠溶胶囊口服后,提高了炎症部位的局部给药浓度,对UC模型大鼠有显著的治疗作用,具有良好的应用前景。OBJECTIVE To prepare alantolactone(ATL)bioadhesive microspheres and investigate its quality characterization,in vitro release mechanism and effects on the ulcerative colitis in rats model.METHODS ATL bioadhesive microspheres were prepared by solvent emulsification and volatilization method,and a series of characterizations such as morphology,particle size,adhesion,encapsulation efficiency,drug loading,X-ray diffraction(XRD)and differential scanning calorimetry(DSC)were carried out.The drug release rate in vitro was measured,and the equations were fitted to explore the drug release mechanism.Rat model of ulcerative colitis(UC)was induced by oxazolone to explore the ATL-OCSDDS therapeutic effects on UC rats.RESULTS Scanning electron microscopy(SEM)results showed ATL microspheres were round with rough surface and intensive micropores left after the solvent evaporating.The average particle size of the ATL bioadhesive microspheres was(205.95±2.72)μm,the adhesion was(91.33±2.52)%,the encapsulation efficiency was(95.54±0.62)%,and the drug loading was(42.62±0.29)%,respectively.XRD and DSC results indicated that most of the ATL were dispersed in the microspheres in amorphous state.The release in vitro reached 89%within 24 h,with the synergistic effects of drug diffusion and skeleton dissolution,mainly diffusion.Administration of ATL microsphere colon-soluble capsules could significantly improve the weight loss,blood in the stool,diarrhea,colon shortening,and spleen edema in UC model rats.It could obviously relieve the colon pathological damage in UC model rats,reduce the expression of myeloperoxidase(MPO)and tumor necrosis factor-α(TNF-α)in UC rats,and increase the expression of IL-4 and IL-13.CONCLUSION The ATL bioadhesive microspheres are successfully prepare with high drug loading.It could increase the local administration concentration in the inflammatory site after oral administration in colon-soluble capsules and have positive therapeutic effects on UC model rats,which has a meaningful application prospect.

关 键 词：土木香内酯 生物黏附微球 口服结肠定位释药系统 溃疡性结肠炎 

分 类 号：R944[医药卫生—药剂学] R965[医药卫生—药学]