促渗剂对白头翁素体外经皮渗透的影响

目的：考察几种常用促渗剂对白头翁素体外经皮渗透性能的影响,为白头翁素经皮给药系统的开发提供参考。方法：采用TK-6A型透皮扩散仪,供应室加含不同促进剂的白头翁素样品,用人皮进行体外经皮渗透实验；以HPLC测定一定时间点接受室中药物浓度,求算累积渗透量及稳态透皮速率。结果：白头翁素饱和水溶液的稳态渗透速率为(1.17±0.03) μg·cm^-2·h^-1,含30%、50%乙醇和3%月桂氮酮-5%聚山梨酯20、30%乙醇-3%月桂氮酮-5%聚山梨酯20的白头翁素溶液稳态渗透速率为(9.30±0.32),(18.56±0.58),(7.29±0.35),(13.77±0.16) μg·cm^-2·h^-1,分别使白头翁素的经皮渗透速率提高了7.9,15.9,6.2,11.8倍。结论：乙醇和月桂氮酮能显著促进白头翁素的经皮渗透,白头翁素有望开发成经皮给药制剂。     

渗透促进剂对马来酸噻吗洛尔角膜透过性的影响

目的：研究渗透促进剂对马来酸噻吗洛尔（TM）角膜透过性的影响。并对其刺激性进行评价。方法：使用双室扩散池方法测定加入6种渗透促进剂后离体兔眼角膜对TM透过量的变化。以角膜水化值和眨眼值频率为指标评价渗透 促进剂的体内外刺激性。结果：0．05％的去氧胆酸钠和1％的泊洛沙姆188分别使TM的表现透过系数增大1．88和1．55倍而未见体内外刺激性。进一步提高泊洛沙姆188浓度抑制药物透过角膜。月桂氮Zhuo酮虽能显著增加TM的透过量却对角膜组织造成损伤。结论：低浓度的去氧胆酸钠和泊洛沙姆188为刺激性小、有效的眼用渗透促进剂。     

冬青油促进蛇床子素和桅子苷透皮吸收的研究

该文拟研究冬青油的体外经皮促渗效果及其作用机制。选择蛇床子素和桅子苷作为亲脂性和亲水性模型药物,利用体外透皮试验测定冬青油的经皮促透效果;采用傅利叶变换红外光谱技术研究冬青油对大鼠皮肤角质层分子结构的影响,并利用扫描电镜直观观察冬青油对大鼠皮肤表皮的影响,探讨其经皮促透机制。结果表明,当冬青油达到一定应用浓度后对蛇床子素和桅子苷均具良好经皮促透效果,但对蛇床子素的促透效果更佳,接近于常用经典促透剂月桂氮酮;红外光谱和扫描电镜研究显示,冬青油主要作用于皮肤角质层脂质,降低角质层致密排列,从而降低皮肤屏障作用。由此可知,冬青油作为促透剂可有效增加亲脂性和亲水性药物的透皮吸收,且对亲脂性药物促透效果更佳,这与其作用于皮肤角质层脂质而改变皮肤表层致密结构有关。     

中药透皮吸收促进剂的研究进展

中药透皮吸收促进剂具有起效快、效果好、副作用小、无污染等优点,总结近年来常用中药透皮吸收促进剂的研究进展,中药透皮吸收促进剂主要包括单一中药透皮吸收促进剂和含中药PE多元透皮吸收促进剂,并对存在的问题及今后的研究前景进行了思考和展望。     

Effect of Iontophoresis in Combination with Ionic Enhancers on the Lipid Structure of the Stratum Corneum: An X-ray Diffraction Study

Pharmaceutical Research -     

A natural lipopeptide of surfactin for oral delivery of insulin

Abstract

Surfactin, a natural lipopeptide produced by Bacillus, is gaining attention for potentially biomedical and pharmaceutical applications. Here, surfactin was assayed for oral delivery of insulin (INS) by its ability to bind to and promote protein to penetrate through the cell membrane. Analysis by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, surfactin was found to form co-precipitates with INS to protect it from acidic and enzymatic attack in the gastrointestinal tract. Further analysis by non-reductive electrophoresis showed surfactin could bind to INS forming heteropolymers. Analysis with circular dichroism, we found this binding significantly influenced the INS structure with decreased rigid α-helix and β-turn, but with increased flexible β-sheet and random coil. The change with more flexible structure was favorable for INS to penetrate through the cell membrane. Fluorescence spectra analysis also showed surfactin could lead Phe and Tyr in the inner of INS exposed outside, further promoting INS permeabilization by improving the hydrophobic-lipophilic interactions between INS and cell membrane. As a result, the effective permeability (Peff) of INS plus surfactin was 4.3 times of that of INS alone. In vivo assay showed oral INS with surfactin displayed excellent hypoglycemic effects with a relative bioavailability of 12.48% and 5.97% in diabetic mice and non-diabetic dogs, respectively. Summary, surfactin is potential for oral delivery of INS by its role as an effective protease inhibitor and permeability enhancer.     

Insulin-loaded alginic acid nanoparticles for sublingual delivery

Abstract

Alginic acid nanoparticles (NPs) containing insulin, with nicotinamide as permeation enhancer were developed for sublingual delivery. The lower concentration of proteolytic enzymes, lower thickness and enhanced retention due to bioadhesive property, were relied on for enhanced insulin absorption. Insulin-loaded NPs were prepared by mild and aqueous based nanoprecipitation process. NPs were negatively charged and had a mean size of ～200?nm with low dispersity index. Insulin loading capacities of >95% suggested a high association of insulin with alginic acid. Fourier Transform Infra-Red Spectroscopy (FTIR) spectra and DSC (Differential Scanning Calorimetry) thermogram of insulin-loaded NPs revealed the association of insulin with alginic acid. Circular dichroism (CD) spectra confirmed conformational stability, while HPLC analysis confirmed chemical stability of insulin in the NPs. Sublingually delivered NPs with nicotinamide exhibited high pharmacological availability (>100%) and bioavailability (>80%) at a dose of 5?IU/kg. The high absolute pharmacological availability of 20.2% and bioavailability of 24.1% in comparison with subcutaneous injection at 1?IU/kg, in the streptozotocin-induced diabetic rat model, suggest the insulin-loaded alginic acid NPs as a promising sublingual delivery system of insulin.     

Assessing the selective therapeutic efficacy of superparamagnetic erlotinib nanoparticles in lung cancer by using quantitative magnetic resonance imaging and a nuclear factor kappa-B reporter gene system

Non-small-cell lung cancer (NSCLC) is the most common type of lung cancer. Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors are commonly used as the first-line treatment for advanced NSCLC; however, the efficacy of drug delivery remains unknown. Hence, we successfully developed erlotinib-conjugated iron oxide nanoparticles (FeDC-E NPs) as theranostic probe that can potentially provide a new avenue for monitoring drug delivering through noninvasive magnetic resonance imaging. MRI ΔR2* relaxivity measurements offer an opportunity to quantitatively evaluate the uptake of FeDC-E NPs at cellular and tumoral levels. Additionally, NF-κB reporter gene system provides NF-κB activation status monitoring to validate the therapeutic efficiency of FeDC-E NPs. FeDC-E NPs not only inhibit the tumor growth and NF-κB-modulated antiapoptotic mechanism but also trigger extrinsic and intrinsic apoptotic pathways. Taken together, dual functional FeDC-E NPs offer diagnostic and therapeutic benefits against lung cancers, indicating that our presented probe could be applied in clinical.     

皮肤创面无机诱导活性敷料对股动脉穿刺后血管并发症止痛效果观察

目的：观察皮肤创面无机诱导活性敷料对股动脉介入术后血管并发症止痛效果。方法：将股动脉穿刺处并发出血、淤血、血肿导致穿刺伤口剧烈疼痛的40例患者随机分为实验组和对照组,实验组以皮肤创面无机诱导活性敷料喷撒型粉剂均匀喷洒伤口,每日2次,连续3d;对照组以传统的磁疗方法治疗15min,每日1次,连续3d。分别记录两种不同治疗方法淤血、血肿部位止痛起效时间,疼痛缓解程度和消肿情况。结果：实验纽和对照组止痛起效平均时间分别为（18．4±6．2）min和（48．5±13．7）min（P〈0．01）;治疗24h后,实验组75％的患者无痛,25％的患者有轻、中度疼痛,对照组100％患者存在轻、中、重度疼痛（P〈0．01）;治疗72h两组血肿疗效比较无显著性差异（P〉0．05）。结论：皮肤创面无机诱导活性敷料用于股动脉穿刺伤口血管并发症治疗止痛效果好,操作简单,有一定的临床应用价值。     

焦谷氨酸油醇酯促进药物经皮吸收活性的研究及其合成

用谷氨酸和油醇合成焦谷氨酸油醇酯。在该化合物作用下替硝唑、咖啡因和 醋酸可的松经皮渗透分别增大了41．8、9．1和2．9倍。