Diaz-Palomera Carlos Daniel, Vidal-Paredes Isaac Alejandro, Navarro-Partida Jose, Cid-Hernandez Margarita, Rosales-Rivera Luis Carlos, De la Rosa-Bibiano Ricardo, Monroy-Ramirez Hugo Christian, Santos Arturo, Armendariz-Borunda Juan
Instituto de Biologia Molecular en Medicina y Terapia Genica, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara 44340, Jalisco, Mexico.
Tecnologico de Monterrey, Escuela de Medicina y Ciencias de la Salud, Monterrey 64849, Nuevo Leon, Mexico.
Pharmaceutics. 2022 Jan 28;14(2):316. doi: 10.3390/pharmaceutics14020316.
Corneal chemical burns (CCBs) frequently result in corneal fibrosis or haze, an opacity of the cornea that obstructs vision and induces corneal blindness. Diverse strategies have been employed to prevent or reduce CCB-related corneal haze. In this study, we evaluated the physicochemical characteristics and biologic effects of a topical pirfenidone (PFD)-loaded liposomal formulation (PL) on a corneal alkali burn mice model. We found that PL was appropriate for ocular application due to its physiologic tear pH, osmolarity and viscosity suitable for topical ophthalmic use. Regarding its therapeutic activity, PL-treated mice had significantly reduced haze size and density, corneal edema, corneal thickness, and corneal inflammatory infiltration, in contrast to PFD in aqueous solution ( < 0.01). Importantly, the antifibrotic activity of PL (reduction of corneal haze) was associated with modulation of transforming growth factor (TGF)-β and Interleukin (IL)-1β genes. PL suppressed TGF-β expression and restored normal IL-1β expression in corneal tissue more efficiently in contrast to PFD in aqueous solution. In conclusion, PFD showed essential anti-inflammatory and anti-fibrotic effects in the treatment of alkali burns. Noteworthy, a new formulation of PFD-loaded liposomes remarkably improved these effects, standing out as a promising treatment for corneal haze.
角膜化学烧伤（CCB）常导致角膜纤维化或混浊，即角膜出现混浊，阻碍视力并导致角膜盲。人们采用了多种策略来预防或减少与CCB相关的角膜混浊。在本研究中，我们评估了局部应用载有吡非尼酮（PFD）的脂质体制剂（PL）对角膜碱烧伤小鼠模型的物理化学特性和生物学效应。我们发现PL因其生理泪液pH值、渗透压和粘度适合局部眼科应用，所以适合眼部给药。关于其治疗活性，与水溶液中的PFD相比（P<0.01），PL治疗的小鼠的混浊大小、密度、角膜水肿、角膜厚度和角膜炎症浸润均显著降低。重要的是，PL的抗纤维化活性（减少角膜混浊）与转化生长因子（TGF）-β和白细胞介素（IL）-1β基因的调节有关。与水溶液中的PFD相比，PL更有效地抑制角膜组织中TGF-β的表达并恢复正常的IL-1β表达。总之，PFD在碱烧伤治疗中显示出重要的抗炎和抗纤维化作用。值得注意的是，一种新的载有PFD的脂质体制剂显著改善了这些作用，成为治疗角膜混浊的一种有前景的方法。
