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Purpose: Supersaturated formulations have been widely explored for improving the oral bioavailability of drugs by using mesoporous silica (MS) to generate supersaturation via molecular adsorption; however, this is followed by precipitation. Several precipitation inhibitors (PI) have been explored to prevent precipitation and maintain the drug in solution for a longer period. However, the combined approach of MS and PIs, the impact of MS and Silica, and the loading of high-molecular-weight neutral molecules such as Cyclosporine A (CsA) have not yet been explored. The present study aimed to explore the impact of MS and a hydroxypropyl methylcellulose (HPMC) matrix on the supersaturation and bioavailability of the neutral drug CsA., Methods: A CsA-loaded mesoporous silica/HPMC ternary matrix and CsA-HPMC and CsA-MS controls were prepared, and physicochemical characterization was carried out. The ternary matrix and controls were investigated for the Non-sink Mini FaSSIF dissolution and biorelevant transfer studies. Furthermore, drug release modeling was performed using DDSolver, and pharmacokinetic studies were performed to assess the impact on oral bioavailability compared with the marketed formulation., Results: The study suggested that the co-loaded CsA, HPMC, and MS demonstrated higher supersaturation than CsA-loaded silica and CsA-HPMC controls. A significant improvement in FaSSIF single medium (2-fold) and biorelevant transfer (3.37-fold) increase in the dissolution profile was observed for the co-loaded CsA-MS-HPMC samples. The in vitro dissolution profile was corroborated by pharmacokinetic studies, which showed a 1.19-fold higher oral bioavailability of CsA-MS-HPMC compared to that of CsA-MS and CsA-HPMC., Conclusion: The pharmacokinetics indicated that CsA-MS-HPMC co-loaded samples demonstrated supersaturation and improved bioavailability compared with the physical mixture.

The eye is a highly sensitive and vital component that significantly affects human quality of life. Diseases that affect the eye are major contributors to visual impairment and blindness and can have a profound effect on an individual's well-being. Ocular drug delivery is challenging because of physiological and anatomical barriers. Invasive Intravitreal administration is primarily used for the treatment and management of posterior segmental disease. However, frequent intravitreal administration is associated with adverse effects. Furthermore, topical administration results in less than 5% ocular bioavailability, leading to a void in the safe and efficacious management of posterior segment diseases. Nanocarrier-based systems have been well explored as ocular therapeutics to overcome the sub-therapeutic management attributed to conventional eye drops and physiological and anatomical barriers. Since the first report of nanoparticles to date, the nanocarrier system has come a long way with the simplicity and versatility offered by the system. Significant progress has been made in the development of noninvasive nanocarrier systems and their interactions with the ocular surface. The nanocarrier system enhances precorneal retention, limits nontherapeutic absorption, and offers controlled drug release. This review aims to provide an overview of the recent advancements in noninvasive nanocarrier-based topical ocular drug delivery systems, including their interaction with the ocular surface, the barriers to their translation to clinical settings, and the associated scale-up challenges., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved.)