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Ocular barriers as a double-edged sword: preventing and facilitating drug delivery to the retina

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Abstract

In recent decades, the growing of the aging population in the world brings increasingly heavy burden of vision-threatening retinal diseases. One of the biggest challenges in the treatment of retinal diseases is the effective drug delivery to the diseased area. Due to the existence of multiple anatomical and physiological barriers of the eye, commonly used oral drugs or topical eye drops cannot effectively reach the retinal lesions. Innovations in new drug formulations and delivery routes have been continuously applied to improve current drug delivery to the back of the eye. Unique ocular anatomical structures or physiological activities on these ocular barriers, in turn, can facilitate drug delivery to the retina if compatible formulations or delivery routes are properly designed or selected. This paper focuses on key barrier structures of the eye and summarizes advances of corresponding drug delivery means to the retina, including various local drug delivery routes by invasive approaches, as well as systemic eye drug delivery by non-invasive approaches.

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Abbreviations

AAV:

Adeno-associated virus

ABC:

ATP-binding cassette

AIDS:

Acquired immune deficiency syndrome

AMD:

Age-related macular degeneration

AUC:

Area under the curve

BRB:

Blood-retinal barrier

BBB:

Blood-brain barrier

iBRB:

Inner blood-retinal barrier

oBRB:

Outer blood-retinal barrier

CNS:

Central nervous system

CNV:

Choroidal neovascularization

DR:

Diabetic retinopathy

FDA:

Food and Drug Administration

GFP:

Green fluorescein protein

HLA:

Human leukocyte antigen

iPSC:

Induced pluripotent stem cells

LAT1:

L-type amino acid transporter 1

mTOR:

Mammalian target of rapamycin

PDGF:

Platelet-derived growth factor

PDS:

Port delivery system

PLGA:

Poly (lactic-co-glycolic) acid

RPE:

Retinal pigment epithelium

SLC:

Solute carrier

siRNA:

Small interfering RNA

shRNA:

Short hairpin RNA

VEGF:

Vascular endothelial growth factor

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Funding

This study was supported by the Science & Technology Department of Sichuan Province (China) funding project (No. 2021YFS0221) and the postdoctoral research funding of West China Hospital, Sichuan University, China (grant number 2020HXBH044).

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  1. Department of Ophthalmology, West China Hospital, Sichuan University, Chengdu, China

    Lixiang Wang

  2. Triapex Laboratories Co., Ltd No. 9 Xinglong Road, Jiangbei New Area, Jiangsu, Nanjing, China

    Hui Zhang

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Wang, L., Zhang, H. Ocular barriers as a double-edged sword: preventing and facilitating drug delivery to the retina. Drug Deliv. and Transl. Res. 13, 547–567 (2023). https://doi.org/10.1007/s13346-022-01231-5

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