Introduction:The development of ophthalmic formulations able to deliver hydrophilic and hydrophobic drugs to the inner structures of the eye and restore the preocular tear film has been a leading topic of discussion over the last few years. In this sense, liposomes represent a suitable strategy to achieve these objectives in ocular drug delivery. Areas covered: Knowledge of the different physiological and anatomical structures of the eye, and specially the ocular surface are critical to better understanding and comprehending the characteristics required for the development of topical ophthalmic liposomal formulations. In this review, several features of liposomes are discussed such as the essential materials used for their fabrication, basic structure and preparation methods, from already established to novel techniques, allowing the control and design of special characteristics. Besides, physicochemical properties, purification processes and important strategies to overcome delivery or encapsulation challenges are also presented. Expert opinion: Regarding ocular drug delivery of liposomes, there are some features that can be re-designed. Specific biocompatible and biodegradable materials presenting therapeutic properties, such as lipidic compounds or polymers significantly change the way of tackling ophthalmic diseases. Besides, liposomes entail an effective, safe and versatile strategy for the treatment of diseases in the clinical practice.

The present study aims to develop a thermo-responsive-injectable hydrogel (HyG) based on PLGA-PEG-PLGA (PLGA = poly-(DL-lactic acid co-glycolic acid); PEG = polyethylene glycol) to deliver neuroprotective agents to the retina over time. Two PLGA-PEG PLGA copolymers with different PEG:LA:GA ratios (1:1.54:23.1 and 1:2.25:22.5) for HyG-1 and HyG-2 development respectively were synthetized and characterized by different techniques (gel permeation chromatography (GPC), nuclear magnetic resonance (NMR), dynamic light scattering (DLS), critical micelle concentration (CMC), gelation and rheological behaviour). According to the physicochemical characterization, HyG-1 was selected for further studies and loaded with anti-inflammatory drugs: dexamethasone (0.2%), and ketorolac (0.5%), alone or in combination with the antioxidants idebenone (1 µM) and D-α-Tocopherol polyethylene glycol 1000 succinate (TPGS) (0.002%). In vitro drug release and cytotoxicity studies were performed for the active substances and hydrogels (loaded and drug-free). A cellular model based on oxidative stress was optimized for anti-inflammatory and antioxidant screening of the formulations by using retinal-pigmented epithelial cell line hTERT (RPE-1). The copolymer 1, used to prepare thermo-responsive HyG-1, showed low polydispersity (PDI = 1.22) and a strong gel behaviour at 25% (w/v) in an isotonic buffer solution close to the vitreous temperature (31–34 °C). Sustained release of dexamethasone and ketorolac was achieved between 47 and 62 days, depending on the composition. HyG-1 was well tolerated (84.5 ± 3.2%) in retinal cells, with values near 100% when the anti-inflammatory and antioxidant agents were included. The combination of idebenone and dexamethasone promoted high oxidative protection in the cells exposed to H2O2, with viability values of 86.2 ± 14.7%. Ketorolac and dexamethasone-based formulations ameliorated the production of TNF-α, showing significant results (p ≤ 0.0001). The hydrogels developed in the present study entail a novel biodegradable tool to treat neurodegenerative processes of the retina overtime.

The combination of acetazolamide-loaded nano-liposomes and Hydroxypropyl methylcellulose (HPMC) with similar components to the preocular tear film in an osmoprotectant media (trehalose and erythritol) is proposed as a novel strategy to increase the ocular bioavailability of poorly soluble drugs. Ophthalmic formulations based on acetazolamide-loaded liposomes, dispersed in the osmoprotectant solution (ACZ-LP) or in combination with HPMC (ACZ-LP-P) were characterized and in vivo evaluated. The pH and tonicity of both formulations resulted in physiological ranges. The inclusion of HPMC produced an increment in viscosity (from 0.9 to 4.7 mPa·s. 64.9 ± 2.6% of acetazolamide initially included in the formulation was retained in vesicles. In both formulations, a similar onset time (1 h) and effective time periods were observed (7 h) after a single instillation (25 μL) in normotensive rabbits’ eyes. The AUC0–8h of the ACZ-LP-P was 1.5-fold higher than of ACZ-LP (p < 0.001) and the maximum hypotensive effect resulted in 1.4-fold higher (p < 0.001). In addition, the formulation of ACZ in the hybrid liposome/HPMC system produced a 30.25-folds total increment in ocular bioavailability, compared with the drug solution. Excellent tolerance in rabbits’ eyes was confirmed during the study.