| Popis: |
Keratitis is a common ophthalmological disease and also a common cause of blindness (second only to cataracts). This disease is routinely treated by topical administration of dexamethasone sodium phosphate (Dexp). However, due to the presence of anatomical and physiological barriers, frequent administration is needed, often resulting in poor patient compliance and diverse side effects. In this work, Dexp was in situ encapsulated into a His6-metal assembly (HmA) to generate Dexp@HmA, which was utilized in the ocular delivery of Dexp. The physicochemical properties of HmA and Dexp@HmA particles were characterized in detail using various techniques such as dynamic light scattering (DLS), scanning electron microscopy (SEM), and UV-vis spectroscopy. Compared to commercial Eudragi and reported PLGA nanoparticles, HmA showed higher encapsulation efficiency (EE%) and higher loading capacity (LC wt %) of Dexp. Dexp@HmA displayed pH-dependent release; after 33 days at pH 5.8, 6.5, and 7.2, 100%, 65%, and 42% of Dexp, respectively, had been released. In addition, HmA and Dexp@HmA showed low cytotoxicity to macrophages and to all common ocular cell types tested. The effect of Dexp@HmA on corneal inflammation was evaluated using in vitro and in vivo models. Our results demonstrate that Dexp@HmA is much superior to free Dexp in both in vitro and in vivo models. These positive results suggest that HmA may represent a promising candidate nanocarrier for the treatment of various diseases of the anterior segment of the eye. |
