An Update on Strategies to Deliver Protein and Peptide Drugs to the Eye

Abstract

In the past few decades, advancements in protein engineering, biotechnology, and structural biochemistry have resulted in the discovery of various techniques that enhanced the production yield of proteins, targetability, circulating half-life, product purity, and functionality of proteins and peptides. As a result, the utilization of proteins and peptides has increased in the treatment of many conditions, including ocular diseases. Ocular delivery of large molecules poses several challenges due to their high molecular weight, hydrophilicity, unstable nature, and poor permeation through cellular and enzymatic barriers. The use of novel strategies for delivering protein and peptides such as glycoengineering, PEGylation, Fc-fusion, chitosan nanoparticles, and liposomes have improved the efficacy, safety, and stability, which consequently expanded the therapeutic potential of proteins. This review article highlights various proteins and peptides that are useful in ocular disorders, challenges in their delivery to the eye, and strategies to enhance ocular bioavailability using novel delivery approaches. In addition, a few futuristic approaches that will assist in the ocular delivery of proteins and peptides were also discussed.

Figure 1

Projected growth of the therapeutic protein market.

Figure 2

Mechanism of action of bevacizumab.

Figure 3

Mechanism of action of anti-TNF-α agents.

Figure 4

Ways through which proteins and peptides degrade.

Figure 5

Barriers to ocular drug delivery along with routes of ocular drug delivery. Reproduced with permission from Patel C et al., CC BY 4.0.

Figure 6

Novel approaches for ocular delivery of protein and peptides.

Figure 7

(A) In vivo imaging of SD rats after intravitreal injection of Cy7-labled bevacizumab (CB) and Cy7-labled bevacizumab multivesicular liposomes (CB-MVLs) at 0.5, 1, 3, 7, and 14 days, respectively. (B) The concentrations of bevacizumab multivesicular liposomes (Bev-MVLs) and bevacizumab solution (Bev-S) at 3, 7, 14, 21, 28, 42, and 56 days in the vitreous humor, and (C) in aqueous humor. (D) The comparison of bevacizumab concentrations between the vitreous and aqueous humor after intravitreal injection of Bev-MVLs, and (E) of Bev-S (mean ± SD, n = 3). Reproduced with permission from Mu et al. CC BY 4.0.

Figure 8

Types of lipid nanoparticles: (a) liposomes, (b) solid lipid nanoparticles, and (c) nanostructured lipid carrier. Reproduced with permission from Xu et al. CC BY 4.0.