川芪眼用微乳原位凝胶的流变学及释放动力学分析

目的:研究考察川芪眼用微乳原位凝胶的流变学及释放动力学行为,为该制剂的后续研究与开发提供参考。方法:使用MCR 102型流变仪考察川芪眼用微乳原位凝胶的流体性质及线性粘弹区域。体外释放度采用改良Franz扩散池法,以半透膜为释放膜,川芎嗪、藁本内酯为指标成分,取样时间点分别为0.5,1,2,4,6,8 h。结果:川芪眼用微乳原位凝胶是一种假塑性流体并存在线性粘弹区域。以剪切力为指标,确定的线性粘弹区域为0~302.74 Pa,以形变为指标得到的线性粘弹区域范围为0~7.45%。在临界点时,其储能模量(G')等于损耗模量(G″),均为2 976.60 Pa;临界剪切力为302.74 Pa;临界形变7.45%。8 h内6份样品中川芎嗪的平均累积释放量33.71μg,平均累积释放率90.08%,释放动力学遵循Higuchi方程。8 h内6份样品中藁本内酯平均累积释放量为68.46μg,平均累积释放率为84.32%,其释放动力学遵循零级动力学方程。结论:川芪眼用微乳原位凝胶具有较好的粘弹性,并在一定范围内可以发生可逆形变。川芎嗪释放动力学是川芎嗪的理化性质与基质骨架共同作用的结果,藁本内酯的释放动力学主要受其理化性质的影响。     

Acute and sub-chronic toxicity studies of honokiol microemulsion

The purpose of this study was to investigate the acute and sub-chronic toxicity of honokiol microemulsion. In the acute toxicity tests, the mice were intravenously injected graded doses of honokiol microemulsion and were observed for toxic symptoms and mortality daily for 14 days. In the sub-chronic toxicity study, rats were injected honokiol microemulsion at doses of 100, 500, 2500 μg/kg body weight (BW) for 30 days. After 30 days treatment and 14 days recovery, the rats were sacrificed for hematological, biochemical and histological examination. In the acute toxicity tests, the estimated median lethal dosage (LD₅₀) was 50.5 mg/kg body weight in mice. In the sub-chronic toxicity tests, the non-toxic reaction dose was 500 μg/kg body weight. In each treatment group, degeneration or/and necrosis in vascular endothelial cells and structure change of vessel wall can be observed in the injection site (cauda vein) of a few animals while there were no changes in the vessels of other organs. The overall findings of this study indicate that the honokiol microemulsion is non-toxic up to 500 μg/kg body weight, and it has irritation to the vascular of the injection site which should be paid attention to in clinical medication.     

益母草碱油包油微乳在小鼠体内组织分布研究

目的 探讨益母草碱油包油微乳剂和益母草碱混悬剂在动物体内药物代谢动力学特征和组织靶向性。方法 采用高效液相色谱法测定小鼠血浆与组织中益母草碱浓度,计算药物代谢动力学参数。结果 与混悬剂比较,益母草碱微乳剂在体内平均滞留时间提高了7 h,其相对生物利用度为550.684%;益母草碱微乳剂AUC(0→∞)在小鼠各组织的分布整体提高到混悬组的3.626~26.265倍;益母草碱微乳剂在心、肺和脑组织的靶向指标分别为1.044、1.335和4.772。结论 益母草碱油包油微乳提高了生物利用度,对脑组织具有较好的趋向性分布。     

星点设计-效应面法优化鹿角灵芝微乳超声提取工艺

目的 探讨以微乳超声法同时提取鹿角灵芝中灵芝酸和灵芝多糖的最佳条件。方法 采用星点设计-效应面法,以物料溶剂比(X₁)、超声提取时间(X₂)和超声功率(X₃)作为考察因素,以灵芝酸A、灵芝酸C₂、灵芝多糖含量和提取物得率为考察指标,并对考察因素和考察指标总评归一值进行多元线性回归和二项式拟合,以效应面优选最佳的微乳超声提取工艺,并做验证试验。结果 微乳超声提取鹿角灵芝的最佳条件为物料溶剂比1∶18、超声提取时间59 min、超声功率513 W,此条件下灵芝酸A、灵芝酸C₂、灵芝多糖含量和提取物得率分别为0.647 8,0.108 5,11.20 mg·g^-1和34.28%。结论 微乳超声可同时提取鹿角灵芝中脂溶性和水溶性成分,并且节能、省时、操作简便,为工业化提取鹿角灵芝提供了新途径。     

葛根素与磷脂复合后对葛根素微乳经淋巴转运的影响

目的以实验室前期制备的葛根素磷脂复合物微乳及普通常规微乳,采用乳糜微粒阻断法研究葛根素与磷脂形成复合物后对葛根素微乳经淋巴转运的影响。方法以乳糜微粒阻滞技术阻断药物经淋巴转运,HPLC法测定大鼠血浆中葛根素浓度,通过比较阻断组与未阻断组生物利用度来计算淋巴转运的比例。结果葛根素磷脂复合物微乳的淋巴转运高于普通常规微乳,其淋巴转运比例分别为51.3%、40.6%,葛根素磷脂复合物微乳未阻断组和阻断组的AUC0~12分别为(5.489±1.599)、(2.673±1.153)μg·h/m L,葛根素普通常规微乳的未阻断组和阻断组的AUC0~12分别为(4.158±1.160)、(2.478±1.352)μg·h/m L。结论葛根素与磷脂复合后能够提高葛根素淋巴转运效率,且12 h的生物利用度要高于普通常规微乳。     

复方彻清膏微乳的制备及稳定性研究

目的制备复方彻清膏微乳,并考察其稳定性。方法通过溶解度实验结合单因素考察绘制伪三元相图,筛选处方组成,再以乳化剂、油相和助乳化剂的质量分数为自变量,以微乳粒径和载药量为响应值,采用Box-Behnken设计-效应面法优化处方,并对其稳定性进行考察。结果复方彻清膏微乳的最优处方为聚氧乙烯氢化蓖麻油(RH40)-聚乙二醇400(PEG400)-肉豆蔻酸异丙酯(IPM)-水(0.33∶0.16∶0.16∶0.35),平均载药量为224.17 mg/mL,平均粒径为56.50 nm,在4℃和25℃避光条件下稳定性良好。结论制备得复方彻清膏微乳外观性状良好,载药量高,粒径小,稳定性较好,可明显增加彻清膏挥发油的溶解度。     

大蒜素二烯丙基三硫醚微乳的制备及其对肿瘤细胞增殖与迁移的影响

目的制备大蒜素二烯丙基三硫醚(DATS)微乳(DATS-MEs),评价该微乳载药系统对肿瘤细胞增殖和迁移能力的影响。方法以HS15为乳化剂,PEG400为助乳化剂,DATS作为油相,水滴定法制备DATS水包油微乳;采用四甲基偶氮唑蓝(MTT)法,评价DATS-MEs对小鼠Lewis肺癌(LLC)细胞及小鼠黑色素瘤B16BL6细胞体外增殖的影响;采用划痕实验评价DATS-MEs对LLC细胞及B16BL6细胞体外水平移行能力的影响。结果制备的DATS-MEs稳定,外观澄清透明,分散良好;粒径为(16.72±0.22)nm,多分散系数为0.03±0.01,Zeta电位为(-4.98±0.11)m V,DATS在微乳中的包封率为82.89%,载药量为6.28%,在水中的溶解度与裸药组相比增加了约2 367倍。10、30、50μmol/L的DATS-MEs与大蒜素裸药均能有效抑制LLC细胞和B16BL6细胞的增殖及迁移,并且具有剂量依赖性,其中DATS-MEs的药效强于DATS裸药。结论将DATS制成微乳,可提高其稳定性,可以有效解决DATS在水中溶解性差的问题,对LLC细胞及小鼠黑色素瘤B16BL6细胞具有较好的增殖抑制能力及迁移抑制能力,具有更好的抗肿瘤增殖及转移的潜力。     

微乳在经皮给药系统中的应用

微乳经皮给药是目前国内外药学工作者研究的重点,也是目前药物制剂研发热点之一。本文主要从微乳的组成、促渗机制、微乳在经皮给药中的应用3个方面进行了综述。微乳经皮给药具有很好的应用前景。     

微乳薄层色谱在中药成分分析中的应用

微乳薄层色谱展开效果好、色谱性能稳定、重现性良好,已用于中药材、中药饮片和中成药中黄酮、皂苷、生物碱和糖类等成分的分离鉴定。随着现代分析手段的逐步规范,微乳薄层色谱也应逐步走向规范化,在分析过程中,借鉴各种优化方法对影响微乳薄层色谱色谱行为的因素进行筛选,提高分析效能,拓宽其在中药成分分析中的应用范围。从微乳薄层色谱法的特点和优势、微乳液形成规律、所分析成分的种类、品种分布、微乳液的种类及其比例等方面综述微乳薄层色谱在中药成分分析中的应用进展,为中药（单味和复方）专属性鉴别方法的研究提供参考。     

AS1411 Aptamer/Hyaluronic Acid-Bifunctionalized Microemulsion Co-Loading Shikonin and Docetaxel for Enhanced Antiglioma Therapy

In this study, we developed an AS1411 aptamer/hyaluronic acid-bifunctionalized microemulsion co-loading shikonin and docetaxel (AS1411/SKN&DTX-M). Such microemulsion was capable of penetrating the blood-brain barrier (BBB), targeting CD44/nucleolin-overexpressed glioma, and inhibiting the orthotopic glioma growth. AS1411/SKN&DTX-M showed a spherical morphology with a diameter around 30 nm and rapidly released drugs in the presence of hyaluronidase and mild acid. In the U87 cellular studies, AS1411/SKN&DTX-M elevated the cytotoxicity, enhanced the cellular uptake, and induced the cell apoptosis. In the artificial blood-brain barrier model, the transepithelial electrical resistance was decreased after the treatment with AS1411/SKN&DTX-M and thereby of increasing the apparent permeability coefficient. Furthermore, AS1411/SKN&DTX-M showed a strong inhibition against the formation of cancer stem cell–enriched U87 cell spheroids, in which the expression of CD133 was downregulated significantly. In the biodistribution studies, AS1411/SKN&DTX-M could selectively accumulate in the brains of orthotopic luciferase-transfected U87 glioma tumor–bearing nude mice. Importantly, AS1411/SKN&DTX-M exhibited the overwhelming inhibition of glioma growth of orthotopic luciferase-transfected U87 glioma models and reached the longest survival period among all the treatments. In summary, the codelivery of shikonin and docetaxel using bifunctionalization with hyaluronic acid and AS1411 aptamer offers a promising strategy for dual drug-based combinational antiglioma treatment.