Nanotechnology enters ophthalmic arena

Advancements in nanotechnology are making an entry in ophthalmology and addressing the drug delivery challenge in the eye.



Advancements in nanotechnology are making an entry in ophthalmology and addressing the drug delivery challenge in the eye.

By Malaika I. Hill

Nanotechnology has entered the pharmaceutical arena, playing on the ability to manipulate molecular nanoparticles to significantly improve the delivery of drugs to their intended targets.

A nanoparticle is a particle of microscopic size that is measured in one billionth (10-9) of a meter units. The size of a nanoparticle is on the scale of one 1000th the thickness of a single strand of hair. The small size of a nanoparticle allows it to move through spaces that other particles cannot, such as by penetrating into cells.

Massachusetts Institute of Technology’s Robert Langer, ScD, has been at the forefront of nanotechnology for decades. Dr. Langer has written more than 1,200 articles and has more than 1,000 issued and pending patents worldwide. In addition, he is the recipient of more than 220 major awards-he is one of seven people to receive both the U.S. National Medal of Science and the U.S. National Medal of Technology and Innovation.

Nanotechnology in ophthalmology

Kala Pharmaceuticals Inc., co-founded by Dr. Langer, is developing innovative drug therapy based on nanotechnology that has the ability to rapidly and effectively penetrate mucosal barriers to improve drug delivery to mucus protected tissues and thus improve efficacy and treatment outcomes.

The mucus penetrating particles (MPP) platform technology allows diverse therapeutic agents to pass through the mucus layer of the ocular surface, facilitating penetration into deeper tissues of the eye, including the aqueous humor and retina. MPP allows therapeutic agents to avoid being trapped by the tear film and cleared via blinking, thereby extending the duration and enhancing the penetration of drugs to the site of disease.


Dr. Langer and his research team published some of the earliest peer-reviewed literature on nanotechnology in the 1970s. Two of Dr. Langer’s former students played critical roles in developing MPPs. Justin Hanes, PhD, now a professor at Johns Hopkins University, Baltimore, made the original discovery and Hongming Chen, now the executive vice president of research at Kala, translated the technology from the academic setting to the private biotechnology world and is now leveraging it for the development of breakthrough treatments for eye disease.

Nanotechnology will revolutionize ophthalmology, similar to various other areas of medicine, according to Dr. Langer. He said that he foresees MPP technology-specifically due to its ability to penetrate through mucus layers-to be a great breakthrough for ophthalmology.

“I envision a new kind of eye drop that will tremendously enhance the duration of action and localization of action for delivery to the front or the back of the eye,” Dr. Langer said.

Its applications are potentially unlimited in the ophthalmology arena and include inflammation, blepharitis, dry eye, age-related macular degeneration (AMD), retinal vein occlusion (RVO), and diabetic macular edema (DME).

“Profoundly-because preclinical data indicate that drugs delivered in nanoparticles can find their way to the back of the eye-this technology may also enable some ocular diseases to be treated with eye drops instead of invasive means such as injection, implants, or surgery as Kala is investigating with AMD and other retina diseases via partnerships,” Dr. Langer said.


MPP mechanism of action

MPPs were inspired by nature. Certain virus particles can penetrate through mucus and infect mucus-protected cells whereas others cannot.

Dr. Hanes’s team discovered that the unique characteristics of those viral particles that infect mucus protected cells are that they are all of the nanoparticle size and have surface characteristics that render them hydrophilic and with a net neutral charges.

The size of the virus allows it to penetrate into the pores of the mucus meshwork, and the hydrophilicity and neutral surface charge allows the virus to avoid being bound by the glycosylated macromolecules that populate the interior of the mucus network. The design of the mucus penetration particle platform for drug delivery was based on these observations and years of research.

The MPP platform combines small particle size and surface engineering to achieve particles that can freely diffuse through the tear film barrier (mucus layer). The process features the creation of a nanoparticle consisting of the therapeutic agent, surrounded by surface-engineered polymers that have been preciously used in ocular drug products that allow the nonoparticles to be inert to the mucin fibers. This technology can deliver a wide variety of small molecules.

Other iterations of the platform would also be amenable to the delivery of biologic agents and controlled delivery. In the video, shown here, the mechanism of action is exemplified. (See provided animation)


Clinical trials under way

Kala currently has several products entering clinical trials, beginning with loteprednol etabonate ophthalmic suspension, an ocular corticosteroid that has been previously approved as Lotemax (Bausch + Lomb) for reducing post-ocular pain and inflammation. Kala is utilizing the MPP platform to enhance delivery of loteprednol etabonate for several ocular diseases.

Preclinical data has shown pharmacokinetic and efficacy results for Kala’s 1% formulation of loteprednol etabonate (1% LE-MPP) that are far superior to that of the current loteprednol etabonate products. It is set to enter a pivotal phase II/III clinical study this year for post-operative pain and inflammation after cataract surgery and will be followed by a second phase III trial that will be completed in 2015.

Also set to enter clinical trials this year is a 0.25% loteprednol etabonate-MPP formulation for treatment of dry eye and blepharitis.

In addition, Kala will test the topical delivery of LE-MPP to the back of the eye in a clinical trial this year. Positive results would be a proof of concept for the delivery of drugs to the back of the eye with topical dosing and could broaden the applications for LE-MPP to be used for treating retinal diseases, such as DME and cystoid macular edema (CME).

Finally, Kala is currently selecting clinical candidates from its preclinical phase program focusing on topically applied tyrosine kinase inhibitors coupled with the MPP platform (RTKi-MPP). Researchers are evaluating RTKis that inhibit both vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) for the topical treatment of wet AMD and other retinal diseases.

Kala has also entered multiple collaborations with major ophthalmic companies and is now exploring the possibility of applying MPPs to improve or enable molecules from other companies.


Nanotechnology has broken the boundary for many medical applications. Scientists have created new, revolutionary materials and transcendental techniques for fighting diseases, such as those related to the brain, cancer, and for producing artificial tissues and organs.

We are about to witness nanotechnology making a grand entry in ophthalmology and addressing the drug delivery challenge in the eye, one of the organs of the human body that is best protected. Kala Pharmaceuticals is at the forefront of what could become a new wave of innovative therapeutics for eye disorders with its unique and proprietary MPP nanotechnology in five different indications.

The technology is also being leveraged by corporate partners who are facing a delivery challenge in the eye and are seeking collaborations with Kala. The differentiation already established in preclinical settings suggests that nanotechnology will create breakthrough solutions for patients suffering from diseases.


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