Review

. 2021 Sep 25:607:120924.

doi: 10.1016/j.ijpharm.2021.120924. Epub 2021 Jul 26.

Drug delivery to the anterior segment of the eye: A review of current and future treatment strategies

Affiliations

¹ Department of Chemistry, Stanford University, Palo Alto, CA, USA.
² Institute of Polymeric Materials (IPM), Sahand University of Technology, New Town of Sahand, Tabriz, Iran; Faculty of Polymer Engineering, Sahand University of Technology, New Town of Sahand, Tabriz, Iran.
³ Terasaki Institute for Biomedical Innovation, Los Angeles, CA, USA.
⁴ Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA; Stanford Cardiovascular Institute, Stanford University, CA, USA.
⁵ Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, CA, USA.
⁶ Byers Eye Institute, Stanford University School of Medicine, Palo Alto, CA, USA. Electronic address: yangsun@stanford.edu.
⁷ Byers Eye Institute, Stanford University School of Medicine, Palo Alto, CA, USA. Electronic address: cornea@stanford.edu.
⁸ Byers Eye Institute, Stanford University School of Medicine, Palo Alto, CA, USA. Electronic address: cta@stanford.edu.
⁹ USC Roski Eye Institute, University of Southern California, Los Angeles, CA, USA. Electronic address: Charles.Flowers@med.usc.edu.

PMID: 34324989
PMCID: PMC8579814
DOI: 10.1016/j.ijpharm.2021.120924

Review

Drug delivery to the anterior segment of the eye: A review of current and future treatment strategies

Mohammad Mofidfar et al. Int J Pharm. 2021.

. 2021 Sep 25:607:120924.

doi: 10.1016/j.ijpharm.2021.120924. Epub 2021 Jul 26.

Authors

Affiliations

¹ Department of Chemistry, Stanford University, Palo Alto, CA, USA.
² Institute of Polymeric Materials (IPM), Sahand University of Technology, New Town of Sahand, Tabriz, Iran; Faculty of Polymer Engineering, Sahand University of Technology, New Town of Sahand, Tabriz, Iran.
³ Terasaki Institute for Biomedical Innovation, Los Angeles, CA, USA.
⁴ Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA; Stanford Cardiovascular Institute, Stanford University, CA, USA.
⁵ Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, CA, USA.
⁶ Byers Eye Institute, Stanford University School of Medicine, Palo Alto, CA, USA. Electronic address: yangsun@stanford.edu.
⁷ Byers Eye Institute, Stanford University School of Medicine, Palo Alto, CA, USA. Electronic address: cornea@stanford.edu.
⁸ Byers Eye Institute, Stanford University School of Medicine, Palo Alto, CA, USA. Electronic address: cta@stanford.edu.
⁹ USC Roski Eye Institute, University of Southern California, Los Angeles, CA, USA. Electronic address: Charles.Flowers@med.usc.edu.

PMID: 34324989
PMCID: PMC8579814
DOI: 10.1016/j.ijpharm.2021.120924

Abstract

Research in the development of ophthalmic drug formulations and innovative technologies over the past few decades has been directed at improving the penetration of medications delivered to the eye. Currently, approximately 90% of all ophthalmic drug formulations (e.g. liposomes, micelles) are applied as eye drops. The major challenge of topical eye drops is low bioavailability, need for frequent instillation due to the short half-life, poor drug solubility, and potential side effects. Recent research has been focused on improving topical drug delivery devices by increasing ocular residence time, overcoming physiological and anatomical barriers, and developing medical devices and drug formulations to increase the duration of action of the active drugs. Researchers have developed innovative technologies and formulations ranging from sub-micron to macroscopic size such as prodrugs, enhancers, mucus-penetrating particles (MPPs), therapeutic contact lenses, and collagen corneal shields. Another approach towards the development of effective topical drug delivery is embedding therapeutic formulations in microdevices designed for sustained release of the active drugs. The goal is to optimize the delivery of ophthalmic medications by achieving high drug concentration with prolonged duration of action that is convenient for patients to administer.

Keywords: Cornea-conjunctiva barrier; Formulations; Ocular; Ophthalmic drug-delivery.

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Conflict of interest statement

Declaration of Competing Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

**Fig. 1.**
Historical timeline of major developments in the field of topical ocular drug delivery systems.

**Fig. 2.**
Cross-sectional view of tear film: a high tear turnover rate and gel-like mucin layer make a tear film as a major barrier in topical ocular drug delivery before drug penetration into cornea and corneal barrier.

**Fig. 3.**
Corneal and Conjunctival routes explored for drug delivery to the anterior segment of the eye.

**Fig. 4.**
Hypothetical potential pharmacokinetic profile of topically applied drug concentration in the tear film over time. (A) missed dose, the eye tissue without therapeutic levels of drug over time, (B) toxicity threshold, over administration of drug to its maximum level considered therapeutic, (C) the excessive volume of drug solution increases the drainage rate of instilled volume, and (D) controlled release drug delivery profile with a plateau level of drug distribution of topically applied formulations. Adapted, with permission, from (Ali and Byrne, 2008).

**Fig. 5.**
The feature sizes of materials a) ranging from sub-micron to macroscopic systems as a function of length b) materials of vastly different sizes, ranging from nanometers to centimeters to enable topical ocular delivery of drugs.

**Fig. 6.**
Mechanism of action of mucus penetrating particles (MPP) compared with conventional topical eye drops (Langer and Chen, 2014). Traditional suspension eye drops rapidly clear via blinking on the tear film. MPPs particles diffuse through the tear film into the membrane-bound mucin and ocular surface to reach target tissue. Image Courtesy of Kala Pharmaceuticals.

**Fig. 7.**
Schematics of a) drug diffusion from drug-eluting hydrogel therapeutic contact lens and b) strategies to control drug release from contact lens. Adapted, with permission, from (Choi and Kim, 2018).

See this image and copyright information in PMC

References

1. Addo RT (Ed.), 2016. Ocular Drug Delivery: Advances, Challenges and Applications. Springer International Publishing, Cham.
1. Agarwal R, Iezhitsa I, Agarwal P, Abdul Nasir NA, Razali N, Alyautdin R, Ismail NM, 2016. Liposomes in topical ophthalmic drug delivery: an update. Drug Delivery 23 (4), 1075–1091. - PubMed
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Drug delivery to the anterior segment of the eye: A review of current and future treatment strategies

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Drug delivery to the anterior segment of the eye: A review of current and future treatment strategies

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Conflict of interest statement

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