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含有BX795的离子液体的口服自纳米乳化系统对小鼠的生殖器HSV-2感染有效
Yogesh Sutar1, Sudhanshu Kumar Singh2, Sagar Dhoble1
1Department of Pharmacology and Toxicology, R.K. Coit College of Pharmacy, University of Arizona, Tucson, Arizona 85721, United States.
ACS infectious diseases
|October 9, 2023
概括
将抗病毒BX795转化为离子液体 (IL) 提高了其脂质可溶性,使其能够纳入自我纳米乳化系统 (SNES). 这一策略增强了口服输送,并显著减少了小鼠的单纯疹病毒-2型 (HSV-2) 感染.
科学领域:
- 制药科学 制药科学
- 药物运输 药物运输 药物运输
- 病毒学 病毒学
背景情况:
- BX795是一种有希望的抗病毒候选人,用于简单疹病毒 (HSV) 感染.
- BX795表现出较差的口服生物利用性,由于其低,pH依赖的溶解度和有限的脂质溶解度,阻碍了配方的开发.
- 自行纳米乳化系统 (SNES) 可以提高药物的生物可用性,但BX795的脂质溶解性较差使其纳入SNES复杂化.
研究的目的:
- 为了提高BX795的脂溶性和口服生物可用性,以改善生殖器疹治疗.
- 通过将BX795转化为离子液体 (IL) 并将其纳入SNESs来开发一种新的配方策略.
主要方法:
- BX795被转化为离子液体 (ILs),使用生物相容的离子,如硫酸和酸.
- 评估了BX795 ILs的脂质溶解性和体外特性.
- BX795 文档 (BX795-Doc) 被纳入了 SNES (BX795-Doc-SNES) 中.
- 在实验室中评估了对HSV-2的细胞兼容性和抗病毒活性.
- 口服BX795-Doc-SNES的疗效在HSV-2感染的小鼠模型中进行了评估.
主要成果:
- BX795成功地转化为ILs,其中BX795多酸盐 (BX795-Doc) 显示脂质溶解度增加了约135倍.
- BX795-Doc-SNES在各种pH值范围内容易形成的纳米乳液 (≤200nm).
- BX795-Doc-SNES在体外显示保留了对HSV-2的抗病毒活性,并与BX795.5具有可比的细胞相容性.
- 口服BX795-Doc-SNES显著降低了小鼠的HSV-2感染.
结论:
- 将BX795转化为离子液体是一种有效的策略,可以克服其不良的脂质溶解性.
- 将BX795 ILs纳入SNES增强了口服生物可用性和生殖器疹的治疗疗效.
- 这种方法为开发改善的口服治疗HSV感染提供了一个有希望的途径.
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