Review Article
Nanotherapies for the treatment of ocular diseases

https://doi.org/10.1016/j.ejpb.2015.02.019Get rights and content

Highlights

  • Nanosystems can interact with the ocular mucosa upon topical administration.

  • Improved interactions translate into improved therapeutic efficacies.

  • The potential of nanotechnology has been demonstrated for prevalent ocular diseases.

Abstract

The topical route is the most frequent and preferred way to deliver drugs to the eye. Unfortunately, the very low ocular drug bioavailability (less than 5%) associated with this modality of administration, makes the efficient treatment of several ocular diseases a significant challenge. In the last decades, it has been shown that specific nanocarriers can interact with the ocular mucosa, thereby increasing the retention time of the associated drug onto the eye, as well as its permeability across the corneal and conjunctival epithelium. In this review, we comparatively analyze the mechanism of action and specific potential of the most studied nano-drug delivery carriers. In addition, we present the success achieved until now using a number of nanotherapies for the treatment of the most prevalent ocular pathologies, such as infections, inflammation, dry eye, glaucoma, and retinopathies.

Section snippets

Ocular drug biopharmaceutical barriers

As illustrated in Fig. 1, drugs applied onto the eye need to bypass different biological barriers in order to reach the targeted ocular structures. Firstly, drug molecules are diluted on the precorneal tear film, with an approximate total thickness of 10 μm. It consists of an external lipid layer, an intermediate aqueous layer containing salts, secreted mucins, proteins and metabolic enzymes, and an inner layer, formed principally by lysozymes and cell surface mucins that form a layer known as

Nanocarriers that may help overcome ocular barriers

In general it is accepted that nanotechnology offers the possibility to develop delivery systems particularly adapted to overcome the eye-associated barriers. Namely, ocular drug delivery nanocarriers have shown the capacity to (i) associate a wide variety of drugs, including large biomacromolecules, (ii) reduce the degradation of labile drugs, (iii) increase the residence time of the associated drugs onto the ocular surface, and (iv) improve their interaction with the corneal and conjunctival

Pharmacokinetics and efficacy of ophthalmic nanomedicines

As mentioned in the previous sections, nanotechnology holds potential for topical ocular drug delivery. In this section, we provide detailed information about nanostructures that have been evaluated either ex-vivo, using excised corneas, or in vivo, in different animal models for the treatment of prevalent ocular diseases, including ocular infection and inflammation, dry eye syndrome, glaucoma and some diseases that affect the back of the eye as retinal dystrophy and macular degeneration. This

Clinical trials and marketed formulations

The great efforts devoted to the field of nanotechnology and topical ocular drug delivery have led to a number of formulations that have already reached the market or are in advanced clinical developmental stages, Table 2. Most of the marketed formulations are drug-free nanoemulsions that have been approved for the treatment of dry eye. However, drug-containing formulations are slowly gaining increasing space in ocular therapies.

The first examples refer to nanoemulsions such as Lipimix™

Conclusive remarks

In the last decades, a wide variety of nanosystems have been developed to treat different ocular diseases via topical administration. In general, it can be stated that nanotechnology has proven its potential to (i) provide enhanced residence times in the precorneal area, (ii) improve drug interactions with the ocular surface, (iii) promote the access of drugs to the targeted tissue, and consequently, (iv) increase the therapeutic efficacy. Indeed, as summarized in this review, there are a

Conflict of interest

The authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest or non-financial interest in the subject matter or materials discussed in this manuscript.

Acknowledgments

The authors acknowledge financial support given by the Carlos III Health Institute, Spain (Miguel Servet Program, CP12/03150), the Ministry of Economy and Competitivity (SURFeye RTC-2014-2375-1) and the Xunta de Galicia (Isidro Parga Pondal Program and Competitive reference groups).

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