Role of In Vitro Models for Development of Ophthalmic Delivery Systems.

There is emergent need for in vitro models which are physiologically correct, easy to reproduce, and mimic characteristic functionalities of desired tissue, organ, or diseases state for ophthalmic drug screening, as well as disease modeling. To date, a variety of in vitro models have been developed for the applications ranging from 2D cell culture-based monolayers, multilayer, or co-culture models, to 3-dimensional (3D) organoids, 3D printed and organ on chip systems. Each model has its own pros and cons. While simple models are easier to create, and faster to reproduce, they lack recapitulation of the complex framework, functionalities, and properties of tissues or their subunits. Recent advancements in technologies and integration with tissue engineering and involvement of microfluidic systems have offered novel platforms which can better mimic the in vivo microenvironment, thus possessing potential in transformation of ophthalmic drug development. In this review we summarize existing in vitro ocular models while discussing applicability, drawbacks associated with them, and possible future applications.

Role of Exosomes for Delivery of Chemotherapeutic Drugs.

Exosomes are endogenous extracellular vesicles (30-100 nm) composed with membrane lipid bilayer which carry vesicular proteins, enzymes, mRNA, miRNA and nucleic acids. They act as messengers for intra- and inter-cellular communication. In addition to their physiological roles, exosomes have the potential to encapsulate and deliver small chemotherapeutic drugs and biological molecules such as proteins and nucleic acid-based drugs to the recipient tissue or organs. Due to their biological properties, exosomes have better organotropism, homing capacity, cellular uptake and cargo release ability than other synthetic nano-drug carriers such as liposomes, micelles and nanogels. The secretion of tumor-derived exosomes is increased in the hypoxic and acidic tumor microenvironment, which can be used as a target for nontoxic and nonimmunogenic drug delivery vehicles for various cancers. Moreover, exosomes have the potential to carry both hydrophilic and hydrophobic chemotherapeutic drugs, bypass RES effect and bypass BBB. Exosomes can be isolated from other types of EVs and cell debris based on their size, density and specific surface proteins through ultracentrifugation, density gradient separation, precipitation, immunoaffinity interaction and gel filtration. Drugs can be loaded into exosomes at the biogenesis stage or with the isolated exosomes by incubation, electroporation, extrusion or sonication methods. Finally, exosomal cargo vehicles can be characterized by ultrastructural microscopic analysis. In this review we intend to summarize the inception, structure and function of the exosomes, role of exosomes in immunological regulation and cancer, methods of isolation and characterization of exosomes and products under clinical trials. This review will provide an inclusive insight of exosomes in drug delivery.