Sprecher
Beschreibung
Retinal neurodegenerative diseases are among the leading causes of irreversible vision loss worldwide. siRNA-based gene therapy has emerged as a promising strategy for the treatment of these disorders by selectively silencing disease-associated genes [1,2]. However, the successful clinical translation of siRNA therapeutics is hindered by ocular physiological barriers and rapid drug clearance. Therefore, the development of multifunctional delivery systems capable of protecting siRNA, while ensuring prolonged ocular residence and controlled release, remains a major challenge.
In this work, a thermoresponsive nanocomposite hydrogel for ocular siRNA delivery was developed by combining Pluronic F127 (PL F127), hyaluronic acid (HA), and zinc oxide nanoparticles (ZnO NPs). PL F127 provides an in situ sol-to-gel transition at physiological ocular temperature [3], whereas HA enhances the viscoelastic and mucoadhesive properties of the formulation [4], improving its retention on the ocular surface. ZnO nanoparticles were incorporated as multifunctional components, providing intrinsic photoluminescence for non-invasive carrier tracking together with antibacterial and antimicrobial properties [5].
The influence of polymer concentration, temperature, and formulation composition on the hydrogel microstructure was systematically investigated by Dynamic Light Scattering, ζ-potential measurements, Small-Angle X-ray Scattering, and Small-Angle Neutron Scattering. Structural analyses identified the 15% (w/v) PL F127 formulation as the optimal composition, exhibiting the most pronounced micellar organization, shorter intermicellar distances, and a higher degree of long-range ordering consistent with FCC-like packing. Importantly, the addition of HA and ZnO NPs preserved the ordered self-assembly of the system, demonstrating the robustness of the hydrogel network. The optimized formulation successfully encapsulated siRNA and exhibited sustained release, supporting its potential as an ocular gene delivery system.
Overall, this work demonstrates that the combination of PL F127, HA, and ZnO NPs yields a multifunctional thermoresponsive hydrogel platform for controlled ocular siRNA delivery, while simultaneously providing intrinsic photoluminescence for carrier tracking.
References:
[1] Marchesi N., Fahmideh F., Boschi F., Pascale A., Barbieri A., Cells, 2021, 10, 9.
[2] Zhang X., Li S., Tang Y., Guo Y., Gao S., AAPS PharmSciTech, 2020, 21, 236.
[3] Clerkin S., Singh K., Winning D., Krupa I., Crean J., Brougham D. F., Wychowaniec J. K., J. Mater. Chem. B 2025, 13, 31.
[4] Wang A., Dong L., Guo Z., Sun W., Mi S., Biomed. Mater. 2022, 17, 4.
[5] Gallucci N., Cangiano A., Russo S., Pota G., Di Girolamo R., Martinez E., Vaxelaire N., Paduano L., Vitiello G., Mater. Chem. Front. 2024, 8, 23.