Naltrexone for Ocular Applications: A Mini-Update on Nanocarriers, Patents, and Evidence Analysis

Delivering drugs to the eye remains a significant challenge due to complex anatomical and physiological barriers. Naltrexone (NTX), an opioid receptor antagonist with anti-inflammatory and immunomodulatory properties, has emerged as a promising candidate for ocular therapy. This systematic review examines NTX-based ocular delivery systems advancements, focusing on nanoformulations such as niosomes, hydrogels, in situ gelling films, and polymeric matrices. A literature search (2006-2024) across PubMed, Google Scholar, and Web of Science identified 14 original studies and 4 patents. These formulations improved NTX's solubility, precorneal retention, corneal penetration, sustained release, and photostability. Using the GRADE framework, we found high certainty of evidence for enhanced solubility, retention, sustained release, and safety. Moderate certainty supported NTX's efficacy in diabetic keratopathy, tear production, corneal healing, and ocular bioavailability. Overall, nanoformulated NTX shows strong potential for managing ocular conditions, highlighting the role of advanced delivery systems in improving therapeutic outcomes while minimizing side effects.