全自动透皮扩散系统

帕洛诺司琼贴片的体外透过性能及在大鼠体内的药动学

制备了帕洛诺司琼透皮贴片并考察其体外释放和透过行为，以及在大鼠体内的药动学特征。分别采用 3 种不同类 型的含羟基丙烯酸压敏胶 (PSA-1、PSA-2 和 PSA-3) 制备出 F1、F2、F3 贴片，通过影响因素试验、体外释放和体外透 皮试验进行评价，筛选出优化贴片进行大鼠药动学试验。结果表明，处方 F2 中帕洛诺司琼的有关物质含量明显低于处 方 F1 和 F3，且帕洛诺司琼具有较快的释放速率及较高的体外透过能力，48 h 累积透过率达到 (78.8±11.6)％。F2 贴片的 大鼠药动学试验结果表明，贴片组比市售注射组有更长的消除半衰期 [ (26.4±6.8) h vs.(16.4±5.9) h]，绝对生物利用度为 (33.1±13.2)％。因此，PSA-2 制备的帕洛诺司琼透皮贴片经皮给药的可行性较高。

大麻二酚的经皮促渗方法及相关促渗机制研究

本文采用预混法与预处理法系统性考察了化学促渗剂和高分子表面活性剂 泊洛沙姆 101（P101）对大麻二酚（CBD）经皮渗透的影响；并进一步通过衰减 全反射傅立叶变换红外光谱分析、分子动力学模拟及分子对接等方法，对相关促 渗机制进行了分析。结果表明，相较于预混法，预处理皮肤方法显示出较佳的促 渗效果，其中采用 1% P101 预处理皮肤促渗作用最强，相应促渗系数达到 12.97。 此外，P101 与皮肤角质层中的脂质分子相互作用明显，对接能为-8.85 kcal/mol； 脂质双分子层体系内聚能密度由 4.15×108 kcal/mol 降低至 3.87×108 kcal/mol， 说明 P101 的促渗作用是由于其扰乱了皮肤角质层脂质双分子层的有序结构，增 加了其流动性。该研究对研发 CBD 经皮给药具有重要的指导意义。

电致孔方式对盐酸青藤碱经皮渗透的促进作用

目的：考察盐酸青藤碱（SNH）的经皮渗透性，并通过优化电致孔参数以达到对 SNH 最佳促渗 作用。方法：采用体外扩散池法研究 SNH 的经皮渗透性及电致孔的促渗作用，并通过小鼠在体试验进一步 评估电致孔的促渗效果。结果：在稳态条件下，SNH 在裸鼠去角质皮肤和全皮中的渗透速率分别为 （385.81±12.88），（0.88±0.20） μg·cm-2·h-1，去角质皮肤中的渗透速率约为全皮中的 438 倍；渗透动力学分 析结果表明，SNH 在角质层中的溶解度和扩散系数都比较低，分别为（70.82±9.63）×103 g·m-3 和（3.07±1.52） ×10-14 cm2·s-1；在优化的电致孔条件（电压 72 V，时间 60 min）下，SNH 在小鼠皮肤中的 24 h 累积渗透量达 到（10 008.39±1 961.57） μg·cm-2，稳态渗透速率达（456.01±51.26） μg·cm-2·h-1，与空白组相比分别提高了 5.4 倍和 5.1 倍，皮肤和肌肉中 SNH 的滞留量分别为空白组的 2.0 倍和 1.5 倍。结论：SNH 在角质层中较低 的溶解度和扩散系数是阻碍其经皮渗透的主要因素，电致孔可显著提高 SNH 的经皮渗透，并可以增加 SNH 在小鼠皮肤和肌肉中的滞留量。

Pharmacokinetics and pharmacodynamics of glycyrrhetinic acid with Paeoniflorin after transdermal administration in dysmenorrhea model mice

Background: Glycyrrhetinic acid (GA) and paeoniflorin (PF) are the main active ingredients in Chinese peony- Liquorice Decoction, a widely used Traditional Chinese Medicine. Hypothesis/Purpose: The aim of this work was to investigate the combinatory analgesic effect of GA and PF after percutaneous administration and to define their pharmacokinetic/pharmacodynamic (PK/PD) characteristics. Study design and Methods: GA and PF were produced to transdermal patches based on previous research, and the permeation parameters of GA and PF in the patches were investigated with in vitro experiments. Dysmenorrhea model mice were then produced to compare the analgesic effects of the patches with different proportions of GA-PF. In the in vivo assessment, the number of writhes exhibited by the dysmenorrhea mice was recorded at designated time points, and skin, muscle under skin and plasma samples were collected, for assessments of drug distribution, pharmacokinetics parameters and PK/PD characteristics. Results and conclusion: In dysmenorrhea mice, GA-PF and meloxicam (the positive control drug) could relieve pain to equal degrees. Specifically, a single dose of the optimized patches (10%GA-10%PF, wt) exerted a steady analgesic effect for 48 h in dysmenorrhea mice, but this effect lagged behind the changes in the plasma concentration. Evaluation with the Bliss Independence criterion revealed that the two ingredients displayed a synergistic effect. Then the PK/PD relationship of GA in this compound preparation was defined with this synergistic effect. The preparation might be suitable for topical spasmolysis and anti-inflammatory therapy

Fabrication of pH sensitive amphiphilic hot-melt pressure sensitive adhesives for transdermal drug delivery system

Based on the blend of styrene-isoprene-styrene (SIS) thermoplastic elastomer and acrylic resin Eudragits EPO, amphiphilic hot-melt pressure sensitive adhesives (HMPSAs) were fabricated. Compatibility and micromorphology of SIS/EPO blends (SEBs) were analyzed with differential scanning calorimetry (DSC), atomic force microscopy (AFM) and scanning electron microscopy (SEM). The results showed that when the mass ratio of SIS to EPO was 1:1
1:2, bicontinuous structure was formed. Following the addition of an appropriate amount of polyethylene glycol (PEG), mineral oil and C5 resin, the amphiphilic HMPSAs were prepared. Because of the compatibility between SIS and EPO, as well as the hydrogen bond interaction between EPO and PEG, amphiphilic HMPSAs showed good thermostability. The adhesive performance of HMPSAs was measured with 1801 peeling strength and holding power. Geniposide and oleanolic acid were used as model drugs to investigate drug release behavior. When the mass ratio of PEG to SEB was 13:30
16:30, the HMPSAs could maintain good adhesion performance and achieve continual release of both hydrophilic and lipophilic drugs. In weakly acidic conditions, the HMPSAs exhibited good hygroscopicity and release profile, it was shown that pH sensitive amphiphilic HMPSAs were more suitable for transdermal drug delivery system (TDDS).

New Delivery Route of Gambogic Acid Via Skin for Topical Targeted Therapy of Cutaneous Melanoma and Reduction of Systemic Toxicity

Cutaneous melanoma is the deadliest form of skin cancer, and gambogic acid (GA) exhibits potent antimelanoma activity. However, clinical application of GA via intravenous injection and oral administration is limited by systemic toxicity and rapid metabolism in the blood. Here, we developed a new, topical route of GA delivery for anti-melanoma activity and reduction of systemic toxicity. The results indicated that the barrier of the stratum corneum (SC) and low diffusion of GA in the hydrophilic viable skin (epidermis and dermis) limited the GA penetration through intact skin. The combination of azone (AZ) and propylene glycol (PG) showed obvious synergistic effects on skin penetration by GA via improving the permeability of the SC and greatly increasing the skin accumulation of GA, thereby forming a high drug concentration in the skin and achieving a topical targeted treatment of melanoma. In addition, GA (AZePG) achieved the same anti-melanoma effect via topical delivery as via intravenous injection. Intravenous injection and oral administration of GA induced remarkable pathological changes in various organs in mice, whereas GA was not toxic to various organs or to the skin via topical delivery. These findings indicated that topical administration of GA is an alternative route for melanoma treatment. ? 2021 Published by Elsevier Inc. on behalf of the American Pharmacists Association

汪晴教授科研团队研制的治疗“帕金森病”的长效贴剂创新药获批进入临床试验！

大连理工大学汪晴教授科研团队十年攻关，研发的国家2.2类新药“帕金森病”的长效普拉克索透皮贴剂获得临床研究许可！在临床前药学研究中，该科研团队采用了大连科翔科技研制的搅拌、涂布和渗透等系列实验室仪器和中试设备，以及计算机模拟评价系统，圆满完成各项研究工作，各项实验数据顺利通过了CDE的严格核验。