Surface functionalized mesoporous silica nanoparticles for intravitreal application of tacrolimus
| Autor: | Gracielle Ferreira Andrade, Mayara Rodrigues Brandão de Paiva, Armando Silva-Cunha, Sílvia Ligório Fialho, Lays Fernanda Nunes Dourado, Edésia Martins Barros de Sousa, Brenda Fernanda Moreira Castro |
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| Rok vydání: | 2020 |
| Předmět: |
Cell Survival
Biomedical Engineering Nanoparticle Biocompatible Materials chemical and pharmacologic phenomena 02 engineering and technology Tacrolimus Cell Line Biomaterials 03 medical and health sciences Drug Delivery Systems 0302 clinical medicine stomatognathic system Animals Humans Particle Size Propylamines Chemistry Silanes Mesoporous silica Silicon Dioxide 021001 nanoscience & nanotechnology eye diseases Rats stomatognathic diseases Administration Intravesical 030221 ophthalmology & optometry Nanoparticles sense organs 0210 nano-technology Porosity Nuclear chemistry |
| Zdroj: | Journal of Biomaterials Applications. 35:1019-1033 |
| ISSN: | 1530-8022 0885-3282 |
| DOI: | 10.1177/0885328220977605 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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