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.

Eye Drop with Fas-Blocking Peptide Attenuates Age-Related Macular Degeneration

“…In contrast, in the NaIO 3 -treated mice group, intravitreal injection of FBP resulted in successful FBP delivery to the retina, which was evidenced by strong fluorescence signals in the posterior part of the eye ( Figure 2 B). To enhance the retinal delivery of the FBP peptide without intravitreal administration, we harnessed CPP, previously suggested for ocular peptide delivery [ 51 , 57 , 58 , 59 ]. Cytotoxicity testing in retinal cells revealed lower toxicity for FBP conjugated with six or fewer arginine units (6R-FBP) compared with that of the nona-arginine conjugate (9R) ( Figure S3 ).…”

“…Dynamic ocular barriers involve tear drainage, clearance through conjunctival blood and lymphatic systems, and circulation in choroidal blood and lymphatics, adding layers of complexity to achieving optimal drug distribution [ 49 , 50 ]. Although there are various routes of drug administration, including the use of microcannulas, microcatheters, microneedles, intravitreal injection, and subconjunctival injection, these approaches are often invasive and necessitate repeated injections [ 49 , 51 ]. Accordingly, less invasive topical administration methods, including biodegradable contact lenses and topical eye drops, have been formulated [ 51 ].…”

“…Although there are various routes of drug administration, including the use of microcannulas, microcatheters, microneedles, intravitreal injection, and subconjunctival injection, these approaches are often invasive and necessitate repeated injections [ 49 , 51 ]. Accordingly, less invasive topical administration methods, including biodegradable contact lenses and topical eye drops, have been formulated [ 51 ]. Noninvasive and efficient ocular drug delivery methods, such as eye drops and cell-penetrating peptides (CPPs), are also being explored as alternative formulation strategies.…”

Lipid-Based Nanoparticle Functionalization with Coiled-Coil Peptides for In Vitro and In Vivo Drug Delivery

“…What makes CPPs particularly attractive for pharmaceutical applications is their ability to penetrate some barriers, such as skin, the blood–brain barrier (BBB), and the cornea or conjunctiva of the eyes. , This makes it possible to replace unpleasant, potentially dangerous, and painful injections with creams, drops, and soothing sprays.…”

Long‐Acting Ocular Injectables: Are We Looking In The Right Direction?

“…Cell‐penetrating peptide (CPP)‐drug conjugates have shown promise in delivering numerous ocular therapeutics, including biologics, small molecules, and peptides. [ 54 ] Typically, CPPs consist of fewer than 30 amino acid residues, with a notable abundance of basic amino acids, such as arginine and lysine. They transport a wide range of cargo across ocular cellular membranes while retaining their functional integrity.…”