Abou-Taleb Heba A, Fathalla Zeinab, Naguib Demiana M, Fatease Adel Al, Abdelkader Hamdy
Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Merit University (MUE), Sohag 82755, Egypt.
Department of Pharmaceutics, Faculty of Pharmacy, Minia University, Minia 61519, Egypt.
Pharmaceuticals (Basel). 2023 Sep 11;16(9):1284. doi: 10.3390/ph16091284.
Hormonal replacement therapy is the mainstay treatment to improve quality of life and reduce mortality. With the increasing number of young women with early menopause, women now live longer (increased life expectancy). However, poor patient compliance with oral estrogen therapy has emerged. Intravaginal estrogen therapy can provide significant benefits with minimal risk for postmenopausal women with symptoms of the lower urinary tract and vaginal area but who do not want to take oral estrogen. In this study, estradiol-loaded solid lipid nanoparticles (SLPs) were prepared from compritol ATO 888 and precirol ATO 5, and two different stabilizers (Pluronic F127 and Tween 80) were studied. Selected SLPs (F3 and F6) were coated with different concentrations of the mucoadhesive and sustained-release polymer chitosan. Furthermore, gelation time, viscosity, mucoadhesion, ex vivo permeation, and in vitro irritation for vaginal irritation were studied. Particle sizes ranged between 450-850 nm, and EE% recorded 50-83% for the six SLPs depending on the type and amount of lipids used. Cumulative % drug release was significantly enhanced and was recorded at 51% to 83%, compared to that (less than 20%) for the control suspension of estradiol. Furthermore, extensive thermal gelation and mucoadhesion were recorded for chitosan-coated SLPs. Up to 2.2-fold increases in the permeation parameters for SLPs gels compared to the control suspension gel were recorded, revealing a slight to moderate irritation on Hela cell lines. These findings demonstrated chitosan-coated estradiol SLPs as novel and promising vaginal mucoadhesive hybrid nanogels.
激素替代疗法是改善生活质量和降低死亡率的主要治疗方法。随着早期绝经的年轻女性数量增加，女性现在的寿命更长（预期寿命增加）。然而，患者对口服雌激素治疗的依从性较差。对于有下尿路和阴道区域症状但不想服用口服雌激素的绝经后女性，阴道内雌激素治疗可以在风险最小的情况下提供显著益处。在本研究中，由Compritol ATO 888和Precirol ATO 5制备了载有雌二醇的固体脂质纳米粒（SLP），并研究了两种不同的稳定剂（泊洛沙姆F127和吐温80）。选择的SLP（F3和F6）用不同浓度的粘膜粘附和缓释聚合物壳聚糖包衣。此外，还研究了凝胶化时间、粘度、粘膜粘附性、体外渗透以及阴道刺激性的体外刺激情况。粒径范围在450 - 850nm之间，根据所用脂质的类型和数量，六种SLP的包封率记录为50 - 83%。与雌二醇对照悬浮液（小于20%）相比，累积药物释放显著增强，记录为51%至83%。此外，壳聚糖包衣的SLP记录到广泛的热凝胶化和粘膜粘附性。与对照悬浮液凝胶相比，SLP凝胶的渗透参数增加高达2.2倍，显示对Hela细胞系有轻微至中度刺激。这些发现表明壳聚糖包衣的雌二醇SLP是新型且有前景的阴道粘膜粘附杂化纳米凝胶。
