将纳米弹性体制剂作为一种有前途的方法来提高天然白三烯抑制剂（3-乙酰基-11-酮-β-乳香酸）的局部递送：统计优化、体外特性和体外渗透研究。

Formulation of Nanospanlastics as a Promising Approach for ‎Improving the Topical Delivery of a Natural Leukotriene Inhibitor (3-‎Acetyl-11-Keto-β-Boswellic Acid): Statistical Optimization, in vitro ‎Characterization, and ex vivo Permeation Study.

机构信息

Department of Pharmacognosy, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt.

Department of Pharmaceutical Technology, Faculty of Pharmacy, Kafrelsheikh University, Kafrelsheikh, Egypt.

出版信息

Drug Des Devel Ther. 2020 Sep 15;14:3697-3721. doi: 10.2147/DDDT.S265167. eCollection 2020.

PURPOSE

The current study aimed to discuss the potential of nanospanlastics as a surfactant-based vesicular system for improving the topical delivery of 3-acetyl-11-keto-β-boswellic acid (AKBA). AKBA is a potent anti-inflammatory drug, but it has poor oral bioavailability due to its poor aqueous solubility. Moreover, the topical delivery of AKBA is difficult due to its high lipophilicity. To overcome these drawbacks, AKBA was formulated as deformable elastic nanovesicles and nanospanlastics, for improving its topical delivery.

MATERIALS AND METHODS

AKBA-loaded spanlastic nanovesicles (SNVs) were formulated by ethanol injection technique according to 2 factorial design using Span 60 as a non-ionic surfactant and Tween 80 as edge activator (EA) to investigate the effect of different independent variables on entrapment efficiency (EE%), % drug released after 8 hr (Q) and particle size (PS) using Design-Expert software. In vitro characterization, stability test and ex vivo permeation study of the optimized formula were performed.

RESULTS

The choice of the optimized formula was based on the desirability criteria.‎ F7 was selected as the optimized formula because it has the highest desirability value of 0.648. F7 exhibited EE% of 90.04±0.58%, Q of 96.87±2.67%, PS of 255.8±2.67 nm, and zeta potential of -49.56 mV. F7 appeared as spherical well-defined vesicles in both scanning electron microscope (SEM) and transmission electron microscope (TEM). The Fourier transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC) studies investigated the absence of interaction between AKBA and ‎different excipients and good encapsulation of AKBA within SNVs. F7 retained both physical and chemical stability after storage for 3 months at 4-8 °C. Ex vivo permeation test exhibited significant enhancement of permeability of F7 across rat skin than the free drug.

CONCLUSION

Nanospanlastics could be a promising approach for improving the permeability and topical delivery of AKBA.

目的

本研究旨在探讨纳米弹性塑料作为基于表面活性剂的囊泡系统在提高 3-乙酰-11-酮-β-乳香酸（AKBA）的局部递送上的潜力。AKBA 是一种有效的抗炎药物，但由于其水溶性差，口服生物利用度低。此外，由于 AKBA 的高亲脂性，其局部递送较为困难。为了克服这些缺点，将 AKBA 制成可变形弹性纳米囊泡和纳米弹性塑料，以提高其局部递药效果。

材料与方法

采用乙醇注入法，根据 2 因素设计，以 Span 60 为非离子表面活性剂，Tween 80 为边缘活性剂（EA），制备载 AKBA 的 Spanlastic 纳米囊泡（SNVs），考察不同自变量对包封率（EE%）、8 小时后释放的药物百分比（Q）和粒径（PS）的影响，使用 Design-Expert 软件。对优化后的配方进行体外特性、稳定性试验和体外渗透研究。

结果

根据理想标准选择最佳配方。F7 因其具有最高的理想值 0.648 而被选为最佳配方。F7 的 EE%为 90.04±0.58%，Q 为 96.87±2.67%，PS 为 255.8±2.67nm，Zeta 电位为-49.56mV。F7 在扫描电子显微镜（SEM）和透射电子显微镜（TEM）中均呈球形、形态良好的囊泡。傅里叶变换红外光谱（FTIR）和差示扫描量热法（DSC）研究表明 AKBA 与不同赋形剂之间无相互作用，AKBA 良好地包封于 SNVs 中。F7 在 4-8°C 下储存 3 个月后保持物理和化学稳定性。体外渗透试验表明，F7 显著提高了 AKBA 通过大鼠皮肤的渗透性，优于游离药物。