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Implantable sustained-release drug delivery systems: a revolution for ocular therapeutics

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Abstract

Purpose

Due to the inimitable anatomical structure of the eyeball and various physiological barriers, conventional ocular local administration is often complicated by apparent shortcomings, such as limited bioavailability and short drug retention. Thus, developing methods for sustainable, safe and efficient drug delivery to ocular target sites has long been an urgent need. This study briefly summarizes the barriers to ocular drug administration and various ocular drug delivery routes and highlights recent progress in ocular implantable sustained-release drug delivery systems (DDSs) to provide literature evidence for developing novel ocular implants for sustained drug delivery.

Methods

We conducted a comprehensive search of studies on ocular implantable sustained-release DDSs in PubMed and Web of Science using the following keywords: ocular, implantable and drug delivery system. More than 400 papers were extracted. Publications focused on sustained and controlled drug release were primarily considered. Experimental articles involving DDSs that cannot be implanted into the eye through surgeries and cannot be inserted into ocular tissues in solid form were excluded. Approximately 143 publications were reviewed to summarize the most current information on the subject.

Results

In recent years, numerous ocular sustained-release DDSs using lipids, nanoparticles and hydrogels as carriers have emerged. With unique properties and systematic design, ocular implantable sustained-release DDSs are able to continuously maintain drug release, effectively sustain the therapeutic concentration in target tissues, and substantially enhance the therapeutic efficacy. Nevertheless, few ocular implantable sustained-release DDSs have been available in clinical use.

Conclusions

Ocular implantable sustained-release DDSs have become a new focus in the field of ocular drug development through unique designs and improvements in the materials of drug carriers, administration methods and dosage forms. With more ocular implantable sustained-release DDSs being commercialized, ocular therapeutics may be revolutionized.

Graphical Abstract

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Abbreviations

AMD:

Age-related macular degeneration

BRB:

Blood retinal barrier

CNV:

Choroidal neovascularization

DDS:

Drug delivery system

Dex:

Dexamethasone

DR:

Diabetic retinopathy

FA:

Fluocinolone acetonide

HA:

Hyaluronic acid

ILM:

Inner limiting membrane

MN:

Microneedle

MXF:

Oxifloxacin

PDMS:

Polydimethylsiloxane

PEGDM:

Poly (ethylene glycol) dimethacrylate

pEOEMA:

Poly(2-ethoxyethyl methacrylate)

P-gp:

P-glycoprotein

pHEMA:

Poly(2-hydroxyethyl methacrylate)

PLC:

Poly(D, L-lactide-co-ε-caprolactone)

PLGA:

Polylactic-co-glycolic acid

PVA:

Poly (vinyl alcohol)

Rb:

Retinoblastoma

RPE:

Retinal pigment epithelium

TA:

Triamcinolone acetonide

TEGDM:

Tri (ethylene glycol) dimethacrylate

TPT:

Topotecan

UNO:

Unoprostone

URD:

UNO release device

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Funding

This work was supported by the National Natural Science Foundation of China (No. 82171053, 81570864), and the Natural Science Foundation of Jilin Province (No. 20200801043GH; No. 20190201083JC).

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  1. Department of Ophthalmology, The Second Hospital of Jilin University, Changchun, 130000, China

    Yun-Yi Cong, Bin Fan, Zi-Yuan Zhang & Guang-Yu Li

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All authors contributed to the study conception and design. The first draft of the manuscript was written by Yun-Yi Cong and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Guang-Yu Li.

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Yun-Yi Cong, Bin Fan, Zi-Yuan Zhang and Guang-Yu Li declare they have no financial interests.

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Cong, YY., Fan, B., Zhang, ZY. et al. Implantable sustained-release drug delivery systems: a revolution for ocular therapeutics. Int Ophthalmol 43, 2575–2588 (2023). https://doi.org/10.1007/s10792-023-02637-x

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