A composite System Combining Self-Targeted Carbon Dots and Thermosensitive Hydrogels for Challenging Ocular Drug Delivery.

We developed a composite system combining self-targeted carbon dots and thermosensitive in situ hydrogels for ocular drug delivery of diclofenac sodium (DS). DS-CDC-HP nanoparticles were prepared by loading DS on the surface of CDC-HP via electrostatic interactions. An orthogonal experimental design was selected to screen the optimal thermosensitive hydrogel matrices and then DS-CDC-HP nanoparticles were embedded to form the composite system. The physicochemical properties and release behavior of this system were characterized, and in vivo fluorescence imaging was carried out. Corneal penetrability and in vitro cellular studies (cytotoxicity, cell imaging and cell uptake) were performed to test the feasibility and potential of this ocular delivery system. Finally, the optimal gel matrix consisting of Poloxamer 407: Poloxamer 188: HPMC E50 was 21:1:1 (w/v %), and the gelation temperature before adding artificial tear fluid was 26.67°C and 34.29°C, respectively. This system has the characteristics of biphasic drug release. In addition, the corneal penetrability and in vivo fluorescence study indicated that corneal transmittance was enhanced and drug retention time was extended. Cellular studies revealed that the DS-CDC-HP-Gel has good cytocompatibility and CD44 targeting. In summary, this composite system combines carbon dots with hydrogels, offering new potential for ocular drug delivery.