Tacrolimus (TAC), a potent immunosuppressive macrolide, has been investigated for ocular diseases due to promising results in the treatment of anterior and posterior segments eye diseases. Mesoporous and functionalized silica nanoparticles show potential as TAC delivery platforms owing to their interesting characteristic as large surface area, uniform pore size distribution, high pore volume, and excellent biocompatibility. The purpose of this study was to incorporate TAC in functionalized silica nanoparticles with 3-aminopropyltriethoxysilane (MSNAPTES) and investigate the safety and biocompatibility of the systems. The MSNAPTES and MSNAPTES TAC nanoparticles were characterized. The in vitro cytotoxicity of MSNAPTES and MSNAPTES load with TAC (MSNAPTES-TAC) in retinal pigment epithelial cells (ARPE-19) was determined, chorioallantoic membrane (CAM) assay model was used to investigate the in vivo biocompatibility, and safety of intravitreal injection was evaluated using clinical examination (assessment of intraocular pressure and indirect fundus ophthalmoscopy), electroretinographic (ERG) and histologic studies in rats’ eyes. The elemental analysis (CHN), thermogravimetric (TGA), photon correlation spectroscopy and Fourier transform infrared (FTIR) analysis confirmed the presence of functionalized agent and TAC in the MSNAPTES nanoparticles. TAC loading was estimated at 7% for the MSNAPTES TAC nanoparticles. MSNAPTES and MSNAPTES TAC did not present in vitro cytotoxicity. The drug delivery systems showed good biocompatibility on CAM. No retinal abnormalities, vitreous hemorrhage, neovascularization, retinal detachment, and optic nerve atrophy were observed during the in vivo study. Follow-up ERGs showed no changes in the function of the retina cells after 15 days of intravitreal injection, and histopathologic observations support these findings. In conclusion, MSNAPTES TAC was successfully synthesized, and physicochemical analyses confirmed the presence of TAC in the nanoparticles. In vitro and in vivo studies indicated that MSNAPTES TAC was safe to intravitreal administration. Taking into account the enormous potential of MSNAPTES to carry TAC, this platform could be a promising strategy for TAC ocular drug delivery in the treatment of eye diseases.

他克莫司 (TAC) 是一种有效的免疫抑制大环内酯类药物，由于在前段和后段眼部疾病的治疗中取得了可喜的结果，已被研究用于治疗眼部疾病。介孔和功能化的二氧化硅纳米颗粒具有作为 TAC 传递平台的潜力，因为它们具有有趣的特性，如大表面积、均匀的孔径分布、高孔体积和出色的生物相容性。本研究的目的是将 TAC 与 3-氨基丙基三乙氧基硅烷 (MSNAPTES) 结合到功能化二氧化硅纳米粒子中，并研究系统的安全性和生物相容性。表征了 MSNAPTES 和 MSNAPTES TAC 纳米颗粒。体外的测定了MSNAPTES和MSNAPTES负载TAC（MSNAPTES-TAC）在视网膜色素上皮细胞（ARPE-19）中的细胞毒性，使用绒毛尿囊膜（CAM）测定模型研究体内生物相容性，并评估玻璃体内注射的安全性临床检查（评估眼压和间接眼底检眼镜）、视网膜电图 (ERG) 和大鼠眼睛的组织学研究。元素分析 (CHN)、热重 (TGA)、光子相关光谱和傅里叶变换红外 (FTIR) 分析证实了 MSNAPTES 纳米粒子中存在官能化试剂和 TAC。MSNAPTES TAC 纳米颗粒的 TAC 负载估计为 7%。MSNAPTES 和 MSNAPTES TAC在体外不存在细胞毒性。药物输送系统在 CAM 上显示出良好的生物相容性。在体内研究期间未观察到视网膜异常、玻璃体出血、新生血管形成、视网膜脱离和视神经萎缩。后续的 ERG 显示玻璃体内注射 15 天后视网膜细胞的功能没有变化，组织病理学观察支持这些发现。总之，成功合成了 MSNAPTES TAC，物理化学分析证实了 TAC 在纳米颗粒中的存在。体外和体内研究表明，MSNAPTES TAC 对玻璃体内给药是安全的。考虑到 MSNAPTES 携带 TAC 的巨大潜力，该平台可能成为 TAC 眼部药物递送治疗眼病的有前景的策略。