Ocular Delivery of Therapeutic Agents by Cell-Penetrating Peptides

Abstract

Cell-penetrating peptides (CPPs) are short peptides with the ability to translocate through the cell membrane to facilitate their cellular uptake. CPPs can be used as drug-delivery systems for molecules that are difficult to uptake. Ocular drug delivery is challenging due to the structural and physiological complexity of the eye. CPPs may be tailored to overcome this challenge, facilitating cellular uptake and delivery to the targeted area. Retinal diseases occur at the posterior pole of the eye; thus, intravitreal injections are needed to deliver drugs at an effective concentration in situ. However, frequent injections have risks of causing vision-threatening complications. Recent investigations have focused on developing long-acting drugs and drug delivery systems to reduce the frequency of injections. In fact, conjugation with CPP could deliver FDA-approved drugs to the back of the eye, as seen by topical application in animal models. This review summarizes recent advances in CPPs, protein/peptide-based drugs for eye diseases, and the use of CPPs for drug delivery based on systematic searches in PubMed and clinical trials. We highlight targeted therapies and explore the potential of CPPs and peptide-based drugs for eye diseases.

Keywords: CPP; drug delivery; ocular diseases.

Figure 1

Schemes of the eye structure, common ocular diseases, and ocular drug administration routes. The eye can be divided into an anterior segment and a posterior segment. The anterior segment includes conjunctiva, cornea, anterior and posterior chambers (narrow space behind the iris and in front of the lens). The posterior segment consists of the choroid, retina, and vitreous body. Topical application of ophthalmic formulations is the common route for drug delivery to the anterior segment of the eye for eye diseases that occur at the front of the eye, such as dry eye and glaucoma. Subconjunctival injection can be used for steroid delivery in the setting of ocular inflammation. In contrast, delivery of therapeutic agents to the posterior segment for other eye diseases, including DR, AMD, diabetic macular edema (DME), retinal vein occlusion (RVO), and uveal melanoma, needs invasive administration such as intravitreal, suprachoroidal (microneedle and microcannula), and subretinal injection. Created with BioRender.com.