Chen Z X, Li B, Liu T, Wang X, Zhu Y, Wang L, Wang X H, Niu X, Xiao Y, Sun Q
School of Pharmacy, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang, Liaoning 110122, PR China.
School of Pharmacy, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang, Liaoning 110122, PR China.
Eur J Pharm Sci. 2017 Mar 1;99:240-245. doi: 10.1016/j.ejps.2016.12.026. Epub 2016 Dec 28.
Paeonol shows effective anti-allergic, anti-inflammatory and analgesic activities. However, because of its poor solubility in water and high volatility at room temperature, the application of this drug is restricted in the clinic. The objective of this research was to develop a biocompatible paeonol formulation with improved stability, skin delivery and pharmacokinetic efficiency. In this paper, paeonol-loaded vesicles were prepared using an ethanol injection method. Nano-vesicles were characterized for their physical properties and encapsulation efficiency (EE). Drug permeation behavior in vitro and deposition quantity in porcine ear skin were measured with a Valia-Chien (V-C) diffusion device. Additionally, a validated and sensitive high performance liquid chromatography (HPLC) method was developed to analyze paeonol concentrations in rat plasma after transdermal administration. The results showed that the particle-size order of the nano-vesicles was the following: transethosomes (122.5±7.5nm)<transfersomes (256.5±8.9nm). Compared to the paeonol transfersomes, the transethosomes had a higher EE (85.5±5.2%), and they showed a spherical morphology with a smooth surface when viewed under a transmission electron microscope (TEM). In an in vitro permeation study, the paeonol transethosomes showed an enhanced transdermal flux of 95.7±8.8μg/cm/h and a higher deposition quantity in porcine ear skin compared to the transfersomes. A one-compartment first-order absorption model could be used to describe the pharmacokinetics of paeonol in rats after transdermal administration. The AUC of the paeonol transethosomes was approximately 1.57- and 3.52-fold higher than those of the transfersomes and a saturated solution of paeonol in 35% ethanol, respectively. The results demonstrated that the paeonol transethosomes had a narrow size distribution, high encapsulation efficiency, and long residence in the plasma. This formulation remarkably enhanced the bioavailability of paeonol.
丹皮酚具有有效的抗过敏、抗炎和镇痛活性。然而，由于其在水中溶解度差且在室温下挥发性高，该药物在临床上的应用受到限制。本研究的目的是开发一种具有改善的稳定性、皮肤递送和药代动力学效率的生物相容性丹皮酚制剂。本文采用乙醇注入法制备了载丹皮酚囊泡。对纳米囊泡的物理性质和包封率（EE）进行了表征。用Valia-Chien（V-C）扩散装置测定了体外药物渗透行为和在猪耳皮肤中的沉积量。此外，还建立了一种经过验证的灵敏高效液相色谱（HPLC）方法，用于分析透皮给药后大鼠血浆中丹皮酚的浓度。结果表明，纳米囊泡的粒径顺序为：转乙脂质体（122.5±7.5nm）<传递体（256.5±8.9nm）。与丹皮酚传递体相比，转乙脂质体具有更高的包封率（85.5±5.2%），在透射电子显微镜（TEM）下观察时呈现表面光滑的球形形态。在体外渗透研究中，与传递体相比，丹皮酚转乙脂质体显示出增强的透皮通量，为95.7±8.8μg/cm/h，并且在猪耳皮肤中的沉积量更高。单室一级吸收模型可用于描述透皮给药后大鼠体内丹皮酚的药代动力学。丹皮酚转乙脂质体的AUC分别比传递体和丹皮酚在35%乙醇中的饱和溶液高约1.57倍和3.52倍。结果表明，丹皮酚转乙脂质体具有窄的粒径分布、高的包封率以及在血浆中的长时间滞留。该制剂显著提高了丹皮酚的生物利用度。
