**1. Introduction and objective**

The eyeball may be divided into two parts: the anterior and the posterior segments. The anterior segment consists of the pupil, cornea, iris, ciliary body, aqueous humor, and lens, whereas the posterior segment is comprised of the vitreous humor, macula, retina, choroid, and optic nerve. The retina is the sensitive layer which creates nerve impulses that are transmitted through the optic nerve to the brain. The macula is a specialized area of the retina that is responsible for the central, high-resolution color vision [1]. The retina and macula can suffer from

different disabling illnesses, such as age-related macular degeneration, cystoid macular edema, diabetic retinopathy, and ocular vascular occlusion, which are the leading causes of nonreversible vision impairment [2, 3]. These retinal disorders could be pharmacologically addressed; however, the efficient and safe delivery of drugs to the retinal tissue is not a completely solved subject.

Compared to drug delivery to other organs, ocular drug delivery faces significant challenges posed by various sophisticated ocular barriers. Many of these barriers are inherent and unique to ocular anatomy and physiology, making it a challenging task for drug delivery innovations. Corneal and conjunctival epithelium, bloodaqueous barriers (BAB), and blood-retinal barriers (BRBs) are the fundamental structures that restrict the passage of molecules and fluids to the retina and impede drug penetration; moreover, various elimination mechanisms, such as tear turnover, nasolacrimal drainage, protein binding, systemic absorption, and enzymatic degradation, limit the ocular bioavailability of drugs [4, 5]. Conventional drug administration systems such as eye drops, suspensions, and ointments are optimal in the treatment of the ocular surface (corneal and conjunctiva tissues) and anterior segment disorders. Nevertheless, due to the ocular barriers, drugs barely get into the posterior ocular segment [1]. It is well known that ocular bioavailability after the topical administration of a drug is generally <5% [4, 5].

Therefore, intravitreal (IVT) injections, which circumvent the ocular barriers, are the most frequent pathway to deliver drugs for the treatment of posterior ocular globe disorders. Today, the use of IVT injections has become the most common intraocular procedure worldwide [6] and the standard drug delivery method for the treatment of retinal diseases [2, 3]. Intravitreal injections are now routinely used for the intraocular administration of drugs such as corticosteroids, antimetabolites, antibiotics, and anti-VEGF therapies [7–11].

Although IVT injections are a well-described and feasible route for releasing drugs into the posterior pole of the eye, this procedure is associated with severe complications such as endophthalmitis, lens injury, and retinal detachment [12–14]. Moreover, it might be a burden for physicians, the health system, and patients with poor compliance in many cases [15]. Furthermore, the administration of IVT injections requires highly specialized human resources and special infrastructure, resulting in an expensive therapy option [16]. Research initiatives are continuously being proposed worldwide at fast pace by apex organizations and pharmaceutical companies in order to find a safer and more effective ocular drug delivery method for ocular use.

Nanostructured carriers or nanocarriers (nanomaterials) have proven to be an effective and slightly invasive drug delivery system to keep drug concentrations in the posterior segment of the eyeball, preventing the use of IVT injections or reducing their frequency. The advantage of using nanocarriers is their ability to increase the biopharmaceutical properties of the incorporated drug: solubility, stability, permeability, and retention at the site of application [17].

Nanocarriers are made of nanoparticles (NPs) (1–1000 nm), and they exemplify one of the multiple strategies of nanomedicine, which is interpreted as the application of NPs for medical purposes [18]. The most commonly used materials for NPs include lipids (liposomes), proteins (albumin NPs), cyclic oligosaccharides (cyclodextrins), synthetic polymers (polymeric micelles, dendrimers, hydrogel), and even inorganic compounds (cerium oxide NPs) [19]. Liposomes have been of much interest as carriers for advanced drug delivery in medicine and, especially, in ophthalmology for their potential to avoid the sophisticated ocular barriers, even when they are topically applied. In fact, liposomes and cyclodextrins are the only topically administered nanoparticles that have successfully proven to release corticosteroids in clinical assays [20, 21].

In the following sections, we will review the ocular barriers and routes for ocular drug delivery and discuss the different nanocarriers topically used in preclinical

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**Table 1.**

*Types of barriers for ocular drug delivery.*

*Breaking down the Barrier: Topical Liposomes as Nanocarriers for Drug Delivery…*

studies that have proven to elude the anatomic and physiologic conditions that prevent drugs from reaching the tissues in the posterior segment of the eyeball,

The different barriers that hinder intraocular drug delivery may be classified

The static barriers in the eye are physical barriers that prevent the diffusion of drug molecules into the posterior segment of the eye and the retina. The cornea is a mechanical barrier that comprises the anterior sixth of the eye. This transparent, ellipsoid barrier has different layers that play an important role in drug permeation: each layer offers a different polarity and a potential rate-limiting structure for drug permeation. The corneal epithelium is lipoidal in nature, and it contains 90% of cells in the cornea. These cells are joined by desmosomes and surrounded by ribbonlike tight junctional complexes. The presence of the *zonula occludens* delays paracellular drug permeation from the tear film into intracellular spaces of the epithelium, as well as into the inner layers of the cornea [22]. The epithelium has a significant resistance against the permeation of topical hydrophilic drugs. The highly hydrated stroma that comprises 90% of the corneal layer is made up by an extracellular matrix and a lamellar arrangement of collagen fibrils, and it is an important barrier against the permeation of lipophilic drug molecules. The hexagonal-shaped cells, or endothelium, represent the innermost layer of the cornea, and they have a selective

*DOI: http://dx.doi.org/10.5772/intechopen.86601*

emphasizing the leading role of liposomes.

**2. Barriers for ocular drug delivery**

into three categories (**Table 1**).

**2.1 Static barriers**

*Breaking down the Barrier: Topical Liposomes as Nanocarriers for Drug Delivery… DOI: http://dx.doi.org/10.5772/intechopen.86601*

studies that have proven to elude the anatomic and physiologic conditions that prevent drugs from reaching the tissues in the posterior segment of the eyeball, emphasizing the leading role of liposomes.
