Tag Archives: eye drops

Nanoparticle drug delivery could reduce rejection rates for corneal transplants

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I like pictures of happy researchers and, as these pictures go, the researchers seem pretty relaxed,

Caption: Qingguo Xu, D.Phil., associate professor of pharmaceutics and ophthalmology at VCU School of Pharmacy, (right) in the lab with Tuo Meng, Ph.D., (left) and Vineet Kulkarni. (School of Pharmacy) Credit: VCU School of Pharmacy

A March 23, 2023 Virginia Commonwealth University (VCU) news release (also on EurekAlert) announces work into making corneal transplants more successful, Note: A link has been removed,

Corneal transplants can be the last step to returning clear vision to many patients suffering from eye disease. Each year, approximately 80,000 corneal transplantations take place in the U.S. Worldwide, more than 184,000 corneal transplantation surgeries are performed annually. 

However, rejection rates for the corneal grafts can be as high as 10%. This is largely due to poor patient compliance to the medications, which require frequent administrations of topical eyedrops over a long period of time. 

This becomes especially acute when patients show signs of early rejection of the transplanted corneas. When this occurs, patients need to apply topical eyedrops [sic] hourly to rescue the corneal grafts from failure. 

The tedious process of eyedrop [sic] dosing causes a tremendous burden for patients. The resulting noncompliance to medication treatment can lead to even higher graft-rejection rates. 

Research led by a team at Virginia Commonwealth University may make the corneal grafts more successful by using nanoparticles to encapsulate the medication. The novel approach could significantly improve patient compliance, according to a paper recently published in Science Advances, “Six-month effective treatment of corneal graft rejection.”

Each nanoparticle encapsulates a drug called dexamethasone sodium phosphate, one of the most commonly used corticosteroids for various ocular diseases treatment such as ocular inflammation, non-infectious uveitis, macular edema and corneal neovascularization. By using the nanoparticles to control the release of the medicine over time, patients would require only one injection right after the corneal transplantation surgery without the frequent eye drops. Our studies have shown that using this method the medication maintains its efficacy for six months on a corneal graft rejection model. 

In addition, because the medicine is released slowly and directly where it is most needed, the approach requires much lower doses than current standard eyedrop treatment while providing better efficacy and safety profiles.

Qingguo Xu, D.Phil., the principal investigator of this project and an associate professor of pharmaceutics and ophthalmology at VCU School of Pharmacy, collaborated with Justin Hanes, Ph.D., the Lewis J. Ort professor of ophthalmology at Johns Hopkins University.

Xu said, “To improve patient compliance and treatment efficacy, we developed a tiny nanoparticle (around 200 nanometers) that in animal studies enables the release of the drug up to six months after a single subconjunctival injection along the eyeball.”

Tuo Meng, Ph.D., who worked on the project as a doctoral student at VCU and is the first author of this paper, said: “In our preclinical corneal graft rejection model, the single dosing of the nanoparticle successfully prevented corneal graft rejection for six months.” 

More importantly, the nanoparticle approach reversed signs of early rejection and maintained corneal grafts for six months without rejection. 

This work was supported by the National Eye Institute, National Institutes of Health, through the R01 grant R01EY027827. 

Xu’s lab focuses on developing nanotherapeutics for safer and more effective treatment of various eye diseases.

Here’s a link to and a citation for the paper,

Six-month effective treatment of corneal graft rejection by Tuo Meng, Jinhua Zheng, Min Chen, Yang Zhao, Hadi Sudarjat, Aji Alex M.R., Vineet Kulkarni, Yumin Oh, Shiyu Xia, Zheng Ding, Hyounkoo Han, Nicole Anders, Michelle A. Rudek, Woon Chow, Walter Stark, Laura M. Ensign, Justin Hanes, and Qingguo Xu. Science Advances 22 Mar 2023 Vol 9, Issue 12 DOI: 10.1126/sciadv.adf4608

This paper is open access.

No need for eye drops when your contact lenses can dispense your eye medication

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Anyone who has difficulty getting or allowing drops into their eyes (I once slid out of an ophthalmologist’s examination chair trying to avoid the eye drops he was administering at the end of my appointment) is going appreciate this Dec. 9, 2013 news item on Nanowerk,

For nearly half a century, contact lenses have been proposed as a means of ocular drug delivery that may someday replace eye drops, but achieving controlled drug release has been a significant challenge. Researchers at Massachusetts Eye and Ear/Harvard Medical School Department of Ophthalmology, Boston Children’s Hospital, and the Massachusetts Institute of Technology are one step closer to an eye drop-free reality with the development of a drug-eluting contact lens designed for prolonged delivery of latanoprost, a common drug used for the treatment of glaucoma, the leading cause of irreversible blindness worldwide.

The Dec. 9, 2013 Massachusetts Eye and Ear Infirmary press release (also on EurekAlert), which originated the news item, notes that a lot of people have problems with eye drops and gives a general description of the research,

“In general, eye drops are an inefficient method of drug delivery that has notoriously poor patient adherence. This contact lens design can potentially be used as a treatment for glaucoma and as a platform for other ocular drug delivery applications,” said Joseph Ciolino, M.D, Mass. Eye and Ear cornea specialist and lead author of the paper.

The contacts were designed with materials that are FDA-approved for use on the eye. The latanoprost-eluting contact lenses were created by encapsulating latanoprost-polymer films in commonly used contact lens hydrogel. Their findings are described online and will be in the January 2014 printed issue of Biomaterials.

“The lens we have developed is capable of delivering large amounts of drug at substantially constant rates over weeks to months,” said Professor Daniel Kohane, director of the Laboratory for Biomaterials and Drug Delivery at Boston Children’s Hospital.

In vivo, single contact lenses were able to achieve, for one month, latanoprost concentrations in the aqueous humor that were comparable to those achieved with daily topical latanoprost solution, the current first-line treatment for glaucoma.

The lenses appeared safe in cell culture and animal studies. This is the first contact lens that has been shown to release drugs for this long in animal models.

The newly designed contact lens has a clear central aperture and contains a drug-polymer film in the periphery, which helps to control drug release. The lenses can be made with no refractive power or with the ability to correct the refractive error in near sided or far sided eyes.

Here’s a link to and a citation for the researchers’ published paper,

In vivo performance of a drug-eluting contact lens to treat glaucoma for a month by Joseph B. Ciolino, Cristina F. Stefanescu, Amy E. Ross, Borja Salvador-Culla, Priscila Cortez, Eden M. Ford, Kate A. Wymbs, Sarah L. Sprague, Daniel R. Mascoop, Shireen S. Rudina, Sunia A. Trauger, Fabiano Cade, Daniel S. Kohane. Biomaterials Volume 35, Issue 1, January 2014, Pages 432–439 DOI: S0142961213011150

This article is behind a paywall.