Protein delivery to the back of the eye: barriers, carriers and stability of anti-VEGF proteins.
Utilization of the full clinical potential of many novel therapeutic proteins designed for diseases affecting the posterior segment of the eye has often been limited because of their inherent instability and the difficulty in overcoming various ocular barriers. Intravitreal injection is currently the only approved mode of administration, although it is suboptimal because it is painful and has to be done every 1-2 months as a result of high protein clearance rates from the vitreous humor. In this review, we discuss the status of protein drug delivery to back of the eye in terms of novel protein drugs developed, physiological barriers encountered, strategies for carrier design to overcome these limitations, and protein stability. We focus on the most promising approaches as well as on current shortcomings.
School of Material Science & Engineering, Nanyang Technological University, Singapore. Electronic address: krishna.r@ntu.edu.sg.
Krishna
K
Radhakrishnan
School of Material Science & Engineering, Nanyang Technological University, Singapore.
Nirmal
N
Sonali
School of Material Science & Engineering, Nanyang Technological University, Singapore.
Miguel
M
Moreno
School of Material Science & Engineering, Nanyang Technological University, Singapore.
Jayabalan
J
Nirmal
School of Material Science & Engineering, Nanyang Technological University, Singapore.
Alexandra A
AA
Fernandez
School of Material Science & Engineering, Nanyang Technological University, Singapore.
Subbu
S
Venkatraman
School of Material Science & Engineering, Nanyang Technological University, Singapore; National Healthcare Group Eye Institute, Tan Tock Seng Hospital, Singapore. Electronic address: Rupesh_agrawal@ttsh.com.sg.
Rupesh
R
Agrawal
D000818:Animals; D003692:Delayed-Action Preparations / Q000627:therapeutic use; D004337:Drug Carriers / Q000627:therapeutic use*; D015195:Drug Design; D005123:Eye / Q000378:metabolism*; D005128:Eye Diseases / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D055550:Protein Stability; D021381:Protein Transport; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors*
D003692:Delayed-Action Preparations; D004337:Drug Carriers; D042461:Vascular Endothelial Growth Factor A