RESUMO
Dry eye disease (DED) is a prevalent ocular disorder characterized by unstable tear film condition with loss of aqueous or mucin, excessive oxidative stress, and inflammation, leading to discomfort and potential damage to the ocular surface. Current DED therapies have shown restricted therapeutic effects such as frequent dosing and temporary relief with potential unwanted side effects, urgently necessitating the development of innovative efficient therapeutic approaches. Herein, we developed rosmarinic acid (RosA) conjugated gelatin nanogels loading diquafosol sodium (DQS), DRGNG, for simultaneous ROS-scavenging and mucin-secreting DED treatment. Mechanically, DRGNG suppressed the ROS production, reduced inflammatory factors, and prompted mucin secretion in vitro and in vivo. The whole transcriptome RNA sequencing in vitro further provided a detailed analysis of the upregulation of anti-oxidant, anti-inflammatory, and mucin-promotion pathways. Therapeutically, both in evaporative DED and aqueous deficient DED models, the dual-functional DRGNG could prolong the retention time at the ocular surface, efficiently suppress the oxidative stress response, reverse ocular surface morphology, and recover tear film homeostasis, thus alleviating the DED when the dosage is halved compared to the commercial Diquas®. Our findings contribute to developing innovative therapies for DED and offer insights into the broader applications of nanogels in ocular drug delivery and oxidative stress-related conditions.
RESUMO
Background: Dry eye disease (DED) is a commonly reported ocular complaint that has garnered significant attention in recent research. The global occurrence of DED ranges from 5% to 50%, impacting a substantial proportion of individuals worldwide with increasing frequency. Although topical administration remains the mainstream drug delivery method for ocular diseases, it suffers from drawbacks such as low bioavailability, rapid drug metabolism, and frequent administration requirements. Fortunately, the advancements in nanomedicine offer effective solutions to address the aforementioned issues and provide significant assistance in the treatment of DED. Main text: DED is considered a multifactorial disease of the ocular surface and tear film, in which the integrity of tear film function and structure plays a crucial role in maintaining the homeostasis of the ocular surface. The conventional treatment for DED involves the utilization of artificial tear products, cyclosporin, corticosteroids, mucin secretagogues, and nonsteroidal anti-inflammatory drugs. Furthermore, nanomedicine is presently a significant field of study, with numerous clinical trials underway for various nanotherapeutics including nanoemulsions, nanosuspensions, liposomes, and micelles. Notably, some of these innovative nanoformulations have already received FDA approval as novel remedies for DED, and the advancement of nanomedicine is poised to offer enhanced prospects to solve the shortcomings of existing treatments for DED partially. Conclusions: This article provides an overview of the latest advancements in nanomedicine for DED treatment, while the field of DED treatment is expected to witness a remarkable breakthrough shortly with the development of nanomedicine, bringing promising prospects for patients worldwide suffering conditions.