Akhtar Naheed, Akhtar Naveed, Menaa Farid, Alharbi Walaa, Alaryani Fatima Saad Salem, Alqahtani Ali Musfer, Ahmad Faizan
Department of Pharmacy, Islamia University of Bahawalpur, Bahawalpur 63100, Pakistan.
Department of Nanomedicine, California Innovations Corporation, San Diego, CA 92037, USA.
Gels. 2022 May 30;8(6):335. doi: 10.3390/gels8060335.
Background: Tocopherol acetate (TA) is known as a skin moisturizing and photoprotective agent. One major drawback with tocopherol and its derivatives remains its limited stability. Aim: To develop highly stable TA-containing ethosomal gel (TAEG) as an advanced dosage form. Methods: A cold method technique was used to produce the ethosomes. An in vitro evaluation of viscosity, conductivity, and pH stability was carried out for three months. An in vitro physical characterization of the nanoparticles (NPs) that included particle size (PS), zeta potential (ZP), transmission electron microscopy (TEM), and Fourier-transform infrared (FTIR) spectroscopy analysis was then performed. Organoleptic evaluation, thermostability at 8 °C, 25 °C, 40 °C and 40 °C ± 75% RH, pH, conductivity, viscosity, and spreadability measurements were also performed in vitro for three months. An ex vivo permeation study was performed in phosphate-buffered solution (1× PBS; pH 5.5 or pH 7.4) at 37 ± 0.2 °C by using rat abdominal skin and the Franz diffusion cell method. The data of three independent experiments were expressed as mean ± SD. A two-way ANOVA was applied to compare data on TAEG versus TA control gel (TACG). Results: PS of the ethosomes was in the range of 144−289 nm. A total of nine formulations were developed. Optimized TAEG formulation (TA-5) was selected based on the highest entrapment efficiency (EE) of 99.71%, while the stability, the PS, and the uniformity-based polydispersity index (PDI) were also among the best. TA-5 exhibited smooth spherical ethosomal NPs with PS of 200.6 nm, ZP value of −18.6 V, and PDI of 0.465. Stability data obtained for TA-5 in terms of rheology, conductivity, and pH presented no significant change (p > 0.05) during the entire study duration. Rheological studies indicated that TA-5 followed a non-Newtonian behavior of shear thinning system. The ex vivo drug permeation was 44.55 ± 0.01% in TA-5 and the drug retention in skin was 51.20%, which was significantly higher than TACG as observed after 24 h permeation study (p < 0.05). Conclusions: The newly developed TAEG formulation appears promising to enhance the effectivity of TA and its topical application.
醋酸生育酚（TA）是一种皮肤保湿和光保护剂。生育酚及其衍生物的一个主要缺点是其稳定性有限。目的：开发一种高度稳定的含TA乙醇脂质体凝胶（TAEG）作为一种先进剂型。方法：采用冷法技术制备乙醇脂质体。对其粘度、电导率和pH稳定性进行了为期三个月的体外评估。然后对纳米颗粒（NPs）进行体外物理表征，包括粒径（PS）、zeta电位（ZP）、透射电子显微镜（TEM）和傅里叶变换红外（FTIR）光谱分析。还进行了感官评价、在8℃、25℃、40℃和40℃±75%相对湿度下的热稳定性、pH、电导率、粘度和铺展性测量，体外持续三个月。采用大鼠腹部皮肤和Franz扩散池法，在37±0.2℃的磷酸盐缓冲溶液（1×PBS；pH 5.5或pH 7.4）中进行离体渗透研究。三个独立实验的数据表示为平均值±标准差。应用双向方差分析比较TAEG与TA对照凝胶（TACG）的数据。结果：乙醇脂质体的粒径在144-289nm范围内。共开发了九种制剂。基于99.71%的最高包封率（EE）选择了优化的TAEG制剂（TA-5），同时其稳定性、粒径和基于均匀性的多分散指数（PDI）也处于最佳水平。TA-5呈现出光滑的球形乙醇脂质体纳米颗粒，粒径为200.6nm，ZP值为-18.6V，PDI为0.465。在整个研究期间，TA-5在流变学、电导率和pH方面获得的稳定性数据没有显著变化（p>0.05）。流变学研究表明，TA-5遵循剪切变稀系统的非牛顿行为。在TA-5中，离体药物渗透率为44.55±0.01%，皮肤中的药物保留率为51.20%，在24小时渗透研究后，这一数值显著高于TACG（p<0.05）。结论：新开发 的TAEG制剂在增强TA的有效性及其局部应用方面似乎很有前景。
