Description
The ocular delivery of therapeutic agents is generally restricted by the eye's natural barriers, necessitating advanced drug delivery systems. Novel drug-delivery technologies, such as liposomes, are raising attention as potential ophthalmic drug delivery systems, due to their capacity to encapsulate and efficiently deliver also highly lipophilic drugs. In this respect, the present study strives to develop and produce liposomes formulation able to encapsulate and allow the ophthalmic delivery of Nutlin-3a, a small non-genotoxic inhibitor of the MDM2/p53 interaction, that has shown interesting therapeutic potential against proliferative vitreoretinal diseases. Liposomes were produced via innovative microfluidic approach, and their size distribution was evaluated by dynamic light scattering, and centrifugal field flow fractionation. Nutlin-3a encapsulation efficiency was evaluated via ultrafiltration and HPLC. Moreover, morphological, and structural characterization were conducted using transmission electron microscopy and Fourier-transform infrared spectroscopy, respectively. Through microfluidic formulation studies, phosphatidylcholine liposomes (5.4 and 8.2 mg/mL in 10% ethanol) were selected for their optimal characteristics: a round vesicular structure, a mean size of ~150 nm, low polydispersity (PDI < 0.2), and efficient Nutlin-3a loading. [1]. Biological assays on RPE cell models demonstrated that Nutlin-3a-loaded liposomes significantly reduced cell viability and migration, highlighting their potential for future ophthalmic applications