RESUMO
Purpose: Dry eye disease (DED) is a multifactorial ocular surface disease with a rising incidence. Therefore, it is urgent to construct a reliable and efficient drug delivery system for DED treatment. Methods: In this work, we loaded C-dots nanozyme into a thermosensitive in situ gel to create C-dots@Gel, presenting a promising composite ocular drug delivery system to manage DED. Results: This composite ocular drug delivery system (C-dots@Gel) demonstrated the ability to enhance adherence to the corneal surface and extend the ocular surface retention time, thereby enhancing bioavailability. Furthermore, no discernible ocular surface irritation or systemic toxicity was observed. In the DED mouse model induced by benzalkonium chloride (BAC), it was verified that C-dots@Gel effectively mitigated DED by stabilizing the tear film, prolonging tear secretion, repairing corneal surface damage, and augmenting the population of conjunctival goblet cells. Conclusion: Compared to conventional dosage forms (C-dots), the C-dots@Gel could prolong exhibited enhanced retention time on the ocular surface and increased bioavailability, resulting in a satisfactory therapeutic outcome for DED.
Assuntos
Antioxidantes , Carbono , Córnea , Síndromes do Olho Seco , Hidrogéis , Animais , Síndromes do Olho Seco/tratamento farmacológico , Camundongos , Carbono/química , Antioxidantes/química , Antioxidantes/farmacocinética , Antioxidantes/farmacologia , Antioxidantes/administração & dosagem , Hidrogéis/química , Hidrogéis/administração & dosagem , Hidrogéis/farmacocinética , Córnea/efeitos dos fármacos , Sistemas de Liberação de Medicamentos/métodos , Modelos Animais de Doenças , Disponibilidade Biológica , Lágrimas/efeitos dos fármacos , Lágrimas/química , Compostos de Benzalcônio/química , Compostos de Benzalcônio/administração & dosagem , Compostos de Benzalcônio/farmacocinética , Feminino , Masculino , Temperatura , Pontos Quânticos/químicaRESUMO
Intervertebral disc degeneration (IVDD) is associated with oxidative stress induced reactive oxygen species (ROS) dynamic equilibrium disturbance. Nanozymes, as nanomaterials with enzyme-like activity, can regulate intro-cellular ROS levels. In this study, a new carbon dots nanozyme, N-acetylcysteine-derived carbon dots (NAC-CDs), is developed and proved to be an ideal antioxidant and anti-senescent agent in IVDD management. The results confirmed the NAC-CDs have satisfactory biocompatibility and strong superoxide dismutase (250 U mg-1 ), catalase, glutathioneperoxidase-like activity, and total antioxidant capacity. Then, the powerful free radical scavenging and antioxidant ability of NAC-CDs are demonstrated in vitro as observing the reduced ROS in H2 O2 induced senescent nucleus pulposus cells (NPCs), in which the elimination efficiency of toxic ROS is more than 90%. NAC-CDs also maintained mitochondrial homeostasis and suppressed cellular senescence, subsequently inhibited the expression of inflammatory factors in NPCs. In vivo, evaluations of imaging and tissue morphology assessments suggested that disc height index, magnetic resonance imaging grade and histological score are significantly improved from the degenerative models when NAC-CDs is applied. In conclusion, the study developed a novel carbon dots nanozyme, which efficiently rescues IVDD from ROS induced NPCs senescence and provides a potential strategy in management of IVDD in clinic.
Assuntos
Degeneração do Disco Intervertebral , Núcleo Pulposo , Humanos , Degeneração do Disco Intervertebral/tratamento farmacológico , Degeneração do Disco Intervertebral/metabolismo , Acetilcisteína/farmacologia , Acetilcisteína/metabolismo , Antioxidantes/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Núcleo Pulposo/metabolismo , Núcleo Pulposo/patologiaRESUMO
Developing an efficient antioxidant for anti-inflammatory therapy via scavenging reactive oxygen species (ROS) remains a great challenge owing to the insufficient activity and stability of traditional antioxidants. Herein, we explored and simply synthesized a biocompatible carbon dots (CDs) nanozyme with excellent scavenging activity of ROS for anti-inflammatory therapy. As expected, CDs nanozyme effectively eliminate many kinds of free radicals including â¢OH, O2 â¢- , and ABTS+â¢. Benefiting from multienzyme activities against ROS, CDs nanozyme can decrease the levels of pro-inflammatory cytokines, resulting in good anti-inflammatory effect. Taken together, this study not only sheds light on design of bioactive antioxidants but also broadens the biomedical application of CDs in the treatment of inflammation.