Intraocular injectable hydrogels for the delivery of cells and nanoparticles

The rising global life expectancy has led to a growing prevalence of ophthalmic diseases, while current treatments face important limitations in terms of efficacy, costs, and patient compliance. The use of injectable hydrogels as drug and cell carriers is a promising approach, compared to the injection of drug solutions or cell suspensions. This is because the hydrogel matrix may offer protection against clearance or degradation, may modulate drug/cell release, and provide a biomimetic substrate for differentiating cells while being minimally invasive. On one hand, injectable hydrogels for ocular drug delivery have been traditionally designed to host and release small drugs or proteins. However, limitations such as high burst release and difficulty of entrapping hydrophobic molecules led to the emergence of nanocomposite hydrogels, where the drug is entrapped in nanoparticles prior hydrogel incorporation. Composite systems offer great advantages over the injection of particle suspensions, improving particle fate and drug release kinetics. On the other hand, injectable hydrogels offer a cell-friendly environment to seek tissue regeneration, providing biomechanical and biochemical cues for cellular cross-talk, differentiation, and formation of new extracellular matrix. This review critically discusses recent advancements in the development of novel injectable hydrogels as delivery vehicles for drug-loaded nanoparticles and cells, with a major focus on the formulation components, administration routes, and other factors affecting performance, highlighting promising aspects and challenges to address in the future.