卡波姆制备光甘草定醇质体凝胶的处方筛选及其体外评价的初步研究

目的 以卡波姆940(C-940)为基质,将水难溶性中药黄酮成分光甘草定制备成醇质体凝胶,为难溶性中药的皮肤给药制剂研究提供思路与借鉴。方法 选用C-940作为乙醇、丙二醇、混合醇(乙醇-丙二醇2∶8)三种光甘草定醇质体凝胶基质,对光甘草定醇质体凝胶进行体外评价。结果 C-940浓度为0.4%,所得光甘草定醇质体凝胶呈淡黄色,无分层,黏稠度适中,适宜涂抹。乙醇醇质体凝胶、丙二醇醇质体凝胶、混合醇醇质体凝胶中光甘草定的含量分别为643.09、414.79、615.08μg/g,12 h累积释放量分别为11.11、7.03、6.30μg/cm²,与醇质体释放规律一致,没有改变光甘草定的释放行为。光甘草定醇质体凝胶和凝胶基质对大鼠皮肤都没有刺激性,较安全。结论 以C-940制备的光甘草定醇质体凝胶能有效地改善光甘草定的水溶性,安全性良好。为进一步开发相关的皮肤外用制剂提供基础。     

苦参碱立方液晶纳米粒的制备及质量控制的研究

目的采用改良的高压均质法制备苦参碱立方液晶纳米粒,并建立其质量控制方法。方法以单油酸甘油酯(GMO)为载体材料,洛泊沙姆(F127)为稳定剂,通过高速剪切和超声粉碎制备立方液晶纳米粒。采用高效液相色谱法测定苦参碱的含量。结果苦参碱检测浓度在11.125~178μg/m L范围内,浓度和峰面积线性关系良好。苦参碱立方液晶纳米粒在3个浓度水平下测得的平均回收率分别为102.1%、102.6%、100.5%,RSD分别为1.9%、1.9%、2.1%(n=3);包封率为68%,RSD为2%;实验方法精密度良好。结论该制备工艺简单易行,质量控制方法简单、准确。     

虾青素/天然DNA/壳聚糖纳米粒对紫外诱导的小鼠皮肤光老化的改善作用

目的 探究虾青素/天然DNA/壳聚糖纳米粒（Ast/DC）对紫外诱导的小鼠皮肤光老化的改善作用。方法 分子自组装结合溶剂蒸发法制备Ast/DC。紫外照射脱毛小鼠30 d模拟皮肤光老化,研究Ast/DC对小鼠皮肤表观形态、组织纤维结构以及皮肤中超氧化物歧化酶（SOD）等抗氧化因子表达水平等的影响;并用Franz扩散池模拟透皮吸收过程研究纳米载体对虾青素的经皮递送效果。结果 将平均粒径为266 nm、Zeta电位为32.7 mV的Ast/DC（虾青素有效剂量为1.5 μg?cm-2?d-1）涂抹于紫外照射小鼠的背部,可维持其皮肤正常形态和结构,在角质层厚度、胶原纤维和弹性纤维结构等方面与未经紫外照射小鼠相比无明显差异;并且皮肤组织中的谷胱甘肽（GSH）、SOD和过氧化氢酶（CAT）表达水平较光老化小鼠分别显著提高31.4%、25.1%和41.7%（P＜0.05）。当虾青素有效涂抹剂量低至0.33 μg?cm-2?d-1时,Ast/DC仍能显著提高皮肤组织中的抗氧化因子表达水平,且优于游离虾青素;相较于光老化模型小鼠,低剂量Ast/DC组小鼠和虾青素油（Ast/oil）组小鼠中GSH含量分别提高26.4%和15.1%。同时,Ast/DC的24 h累积透皮吸收量比游离虾青素提高20.7%。结论Ast/DC能有效保护小鼠皮肤,抵御紫外照射引起的皮肤光老化。     

盐酸普萘洛尔立方液晶纳米粒的制备及体外评价

摘要：目的:将盐酸普萘洛尔（PPL·HCl）制备成一种立方液晶纳米制剂,并对其进行体外评价。方法:以粒径、包封率为评价指标,采用注入法制备盐酸普萘洛尔立方液晶纳米粒（PPL·HCl-Cubs）并优化其制备工艺,通过单因素考察及星点设计-效应面法优化最佳处方组成,并对制备的PPL·HCl-Cubs进行粒径、Zeta电位、包封率、载药量、体外释放等研究。结果:优化的最佳制备工艺为:磁力搅拌速度600 r·min-1,搅拌温度20℃,搅拌时间1 h,高压均质压力800 bar,均质次数7次;以制成100 g PPL·HCl-Cubs计,最佳PPL·HCl用量3.5 g,单油酸甘油酯用量9 g,泊洛沙姆407用量1.5 g。最优处方制得的PPL·HCl-Cubs粒径为（106.17±4.03） nm,多分散指数为0.216±0.009,Zeta电位为（-29.73±1.23） mV,包封率为（52.92±1.61）%,载药量为（3.26±0.09）%; PPL·HCl-Cubs呈球状,表面圆滑,为双菱形（Pn3m）立方液晶晶格,体外释放符合Ritger-Peppas方程。结论:本文优化得到的盐酸普萘洛尔立方液晶纳米粒工艺条件及处方配比合理可靠。     

尼美舒利醇质体抗炎镇痛作用与皮肤刺激性研究

目的考察尼美舒利醇质体经皮给药的镇痛抗炎作用及皮肤刺激性。方法采用小鼠热板法和醋酸扭体法观察尼美舒利醇质体的止痛作用;建立大鼠佐剂性关节炎模型,观察尼美舒利醇质体对大鼠足肿胀及滑膜关节组织的影响;利用健康豚鼠观察尼美舒利醇质体皮肤刺激反应。结果与对照组比较,中、高剂量尼美舒利醇质体能明显提高小鼠自身的热痛阈值（P＜0.05）;并能使醋酸致小鼠扭体次数显著减少（P＜0.05）;抗炎实验结果表明,尼美舒利醇质体对佐剂引起的大鼠足肿胀关节炎有明显的抑制作用（P＜0.05）;尼美舒利醇质体对豚鼠无皮肤刺激作用。结论尼美舒利醇质体具有明显的抗炎、镇痛作用,且皮肤刺激性较小,是一种有效的经皮给药制剂。     

Pentapeptide modified ethosomes for enhanced skin retention and topical efficacy activity of indomethacin

Challenges associated with topical analgesics and anti-inflammatory drugs include poor drug penetration and retention at the desired lesion site. Therefore, improving these challenges would help to reduce the toxic and side effects caused by drug absorption into the systemic circulation and improve the therapeutic efficacy of topical therapeutic drugs. Pentapeptide (KTTKS) is a signal peptide in skin tissue, it can be recognized and bound by signal recognition particles. In the current study, we successfully prepared novel indomethacin (IMC) loaded KTTKS-modified ethosomes (IMC-KTTKS-Es), and the physicochemical properties and topical efficacy were investigated. Results showed that the prepared IMC-KTTKS-Es displayed a particle size of about 244 nm, a negative charge, good deformability, and encapsulation efficiency (EE) exceeding 80% for IMC, with a sustained release pattern. In vitro percutaneous permeation studies revealed that the skin retention was increased after the drug was loaded in the IMC-KTTKS-Es. Confocal laser scanning microscopy also showed improved skin retention of IMC-KTTKS-Es. In addition, IMC-KTTKS-Es showed improved topical analgesic and anti-inflammatory activity with no potentially hazardous skin irritation. This study suggested that the IMC-KTTKS-Es might be an effective drug carrier for topical skin therapy with a good safety profile.     

脂质立方液晶纳米粒作为药物载体的研究进展

由两亲性脂质分散在水性环境中自发形成各种几何形态构成的药物输送载体正成为制剂载药系统研究的热点之一。脂质立方液晶纳米粒是一定浓度的两亲性脂质分散在水溶液中自组装成含双连续水区和脂质区的闭合脂质双层“蜂窝状(海绵状)”结构,该独特的内部双水道结构和巨大膜表面积使其能够包封各种不同极性和剂量的药物,具有多样化的药物包裹性。作为药物载体,脂质立方液晶纳米粒还具有载药量大、保护多肽蛋白类药物和制备工艺简单等优点;可口服、局部黏膜和注射等多种途径给药,在多种剂型中有广泛的应用。本文对脂质立方液晶纳米给药系统的研究进行归纳和总结,并展望了脂质立方液晶纳米粒新型药物载体的应用前景。     

两性霉素B立方液晶前体胶囊的制备及释放度考察

目的:制备两性霉素B立方液晶前体胶囊,并考察体外释放度。方法:以单油酸甘油酯为液晶材料、两性霉素B为主药制备了立方液晶前体胶囊;用偏光显微镜及小角衍射表征其吸水后的相态;采用高效液相色谱法测定体外释放度。结果:立方液晶前体胶囊吸水后在偏光显微镜下呈暗背景;小角衍射峰位符合q1∶q2=槡6∶槡8,显示其内部结构为Ia3d(Q230)型立方液晶;立方液晶前体胶囊在含有0.25%十二烷基硫酸钠(SDS)的pH 7.4磷酸盐缓冲液(PBS 7.4溶液)中持续释药达9 h。结论:立方液晶前体胶囊在生理温度下接触水介质后可快速吸水形成立方液晶,并具有一定的缓释作用。     

Ocular delivery of cyclosporine A based on glyceryl monooleate/poloxamer 407 liquid crystalline nanoparticles: preparation,characterization, in vitro corneal penetration and ocular irritation

The purpose of this study was to develop an ophthalmic drug delivery system for cyclosporine A (CsA) based on glyceryl monooleate (GMO)/poloxamer 407 liquid crystalline nanoparticles with reduced ocular irritancy and improved corneal penetration. CsA-loaded liquid crystalline nanoparticles were prepared via fragmentation of a bulk GMO/poloxamer 407 cubic phase gel by high-pressure homogenization and characterized. Corneal permeation and retention was evaluated using modified Franz diffusing cells. Intra-corneal transportation was investigated with fluorescein isothiocyanate (FITC)-labeled liquid crystalline nanoparticles. Ocular irritation was then evaluated using the Draize method. The mean particle size of liquid crystalline nanoparticles was 193.5?nm and the entrapment efficiency was 95.11?±?0.67%. A bicontinuous cubic phase of cubic P-type was determined using cryo-transmission electron microscopy (cryo-TEM) observation and small angle X-ray diffraction (SAXD) analysis. A 1.52-fold increase in J_s and a 2.2-fold increase in corneal retention was achieved by liquid crystalline nanoparticles compared with oil solution. In vitro corneal permeation investigated with FITC-labeled liquid crystalline nanoparticles revealed that CsA penetrated across the cornea under the transportation of liquid crystalline nanoparticles. Liquid crystalline nanoparticles exhibited excellent ocular tolerance in the ocular irritation test. This low-irritant vehicle based on liquid crystalline nanoparticles might be a promising system for effective ocular CsA delivery.     

HPLC法测定新型酪氨酸酶抑制剂UP302乳膏的含量及皮肤表面残留量

目的:建立测定UP302乳膏中UP302含量的HPLC方法,并应用于研究UP302乳膏在大鼠皮肤局部给药后的皮肤残留百分率。方法:采用Phenomenex Luna 5u C18(150 mm×4.6 mm,5μm)色谱柱,柱温35℃;流动相为甲醇-水,以1.0 mL·min-1梯度洗脱;检测波长280 nm;检测时间10 min。UP302对照品用甲醇溶解稀释,乳膏和空白乳膏基质中UP302用甲醇提取。结果:UP302在5～100μg·mL-1的浓度范围内线性关系良好(r=0.9999)。本方法日内日间准确度在98.5%～100.6%,日内日间精密度小于2.4%。结论:本方法专属性强,灵敏度高,重现性好,耐用性好,操作简便,结果准确,可用于UP302乳膏的含量测定,以及乳膏皮肤表面残留量的测定和制剂透皮吸收研究。