Contact Lenses That Dispense Prescription Drugs

EMBARGOED FOR RELEASE: Sunday, March 23, 4:00 p.m., Central Time

Eye diseases like glaucoma could one day be treated by pharmaceuticals delivered through contact lenses. Chemical engineers from the University of Florida say they've been able to make soft contact lenses containing tiny embedded particles that slowly release drugs directly where they're needed.

The research was presented today at the 225th national meeting of the American Chemical Society, the world's largest scientific society, held this week in New Orleans.

"One of the biggest problems with using eye drops to deliver medication to the eyes is that about 95 percent of the medication goes where it's not needed," said Anuj Chauhan, Ph.D., one of the authors of the study.

He said that eye drops applied topically mix with tears, which then drain into the nasal cavity and from there, get into the bloodstream and to other organs, where the drugs can cause serious side effects. For example, Timolol, used to treat glaucoma, can cause heart problems. But drugs contained in a contact lens could be released slowly enough to stay in the eye.

Chauhan and his graduate student and coauthor, Derya Gulsen, have found a way to encapsulate a drug in nanoparticles -- tiny particles much smaller than the eye can see -- which can then be mixed into the contact lens matrix during manufacturing of the lens.

In theory, the disposable, drug-laden contact lenses could be worn for up to two weeks, steadily delivering a supply of the drug directly to the eye where it's needed. Rather than being exposed to a sudden high dose of medication -- from an eye drop, for example -- the patient gets the right amount of medicine all the time.

The same lenses could be used to correct vision while delivering medication. And for a person whose vision doesn't need to be corrected, the lenses could be made without correction.

Chauhan said the process could also be used to incorporate antibiotics into the matrix of a lens, making an extended-wear lens that would leave its wearer less vulnerable to bacterial infections -- a chief drawback of such lenses today.

Other researchers have tried getting drugs into contact lenses, either by soaking the lenses in a drug solution or trapping the drug in a hollow cavity between two pieces of lens material. "But contact lenses soaked in drug solutions are not very effective at delivering medications for extended periods of time," Chauhan said. "Our approach allows us great flexibility in designing controlled drug delivery vehicles that can be tailored to different drugs, but are also effective for extended periods of time."

The lenses are in the very early engineering design stages and have not been tested clinically. "We're in the very preliminary stages of developing this technology right now," Chauhan says. No in vitro or animal testing has yet been done.

The paper on this research, COLL 41, will be presented at 4:00 p.m., Sunday, March 23, at the Morial Convention Center, Room 288, during the symposium, "ACS Award in Colloid and Surface Chemistry Symposium Honoring Clay Radke: Interfacial Phenomena in Biological and Biomedical Systems."

Anuj Chauhan. Ph.D., is an assistant professor of chemical engineering in the Chemical Engineering Department at the University of Florida in Gainesville, Fla.

Derya Gulsen is a graduate student in the Chemical Engineering Department at the University of Florida in Gainesville, Fla.

EMBARGOED FOR RELEASE: Sunday, March 23, 4:00 p.m., Central Time

COLL 41 A novel ophthalmic drug delivery vehicle: Dispersion of nanoparticles in soft contact lens

Derya Gulsen, and Anuj Chauhan, Chemical Engineering Department, University of Florida, Room 237 CHE PO Box 116005, Gainesville, FL 32611

The novel drug delivery systems seek to deliver drugs at a uniform rate for extended periods of time for more convenient, efficient drug delivery and reduced side effects. Our project aims to develop disposable soft contact lenses that can be used as vehicles for such a delivery system. The main idea is to encapsulate the ophthalmic drug formulations in nanoparticles and to disperse these drug-laden particles in the contact lens matrix. We focus on soft hydrogel lenses that are made of poly-2-hydroxyethyl methacrylate (HEMA) synthesized by bulk or solution free radical polymerization. Hydrophobic drugs are entrapped either inside microemulsion drops or liposomes. They are then incorporated into hydrogel matrix by subsequent polymerization from which they will diffuse into eye. We considered four kinds of O/W microemulsions: Tween 80 and Panadon SDK; Brij 97; Brij 97 and OTMS, and Tween 80, Panadon SDK and OTMS. The first two of these microemulsion systems become unstable on addition of HEMA monomers due to solubility of the surfactants in HEMA, leading to an opaque gel. The third and the fourth systems are stable due to a monolayer of silica around the oil drop that slows down the aggregation of microemulsion drops after HEMA addition. We characterize the particle-laden hydrogel by swelling, light-transmission and electron microscopy studies. The trapped particles in the hydrogel matrix are about 200 nm in size, which is smaller than the wavelength of the visible light rendering the gel transparent. After synthesizing the gel, we measured the drug release rates of a model hydrophobic drug, Lidocaine, and show that our proposed system can deliver therapeutic levels of drug for about 5 days. The drug delivery rates can be controlled by tailoring the microstructure of the hydrogel and manipulating the size, concentration and structure of the nanoparticles. Keywords: Microemulsions, ophthalmic drug-delivery, contact lenses, hydrogel, HEMA

EMBARGOED FOR RELEASE: Sunday, March 23, 4:00 p.m., Central Time

COLL 41 A novel ophthalmic drug delivery vehicle: Dispersion of nanoparticles in soft contact lens

* Briefly explain in lay language what you have done, why it is significant and its implications, particularly to the general public.

Providing and maintaining adequate concentration of drugs in the pre-corneal tear film for extended periods of time is one of the major problems in ocular drug delivery. When drugs are applied as eye drops, they penetrate poorly through the cornea. Furthermore, drainage of the drug with the tear fluid, and absorption through the conjunctiva leads to a short duration of action. Additionally, the rate of corneal uptake is high at early times, but it declines rapidly. This may lead to a transient period of overdose and associated risk of side effects followed by an extended period of sub-therapeutic levels before the administration of next dose. All the above factors indicate the need for an ocular drug delivery system that will be as convenient as a drop but will serve as a controlled release vehicle.

Topical delivery via eye drops that accounts for about 90% of all ophthalmic formulations is very inefficient and in some instances leads to serious side effects. Only about 5% of the drug applied as drops penetrate through the cornea and reaches the ocular tissue, while the rest is lost due to tear drainage. The drug mixes with the fluid present in the tear film upon instillation and has a short residence time of about 2 minutes in the film. About 5% of the drug gets absorbed and the remaining flows through the upper and the lower canaliculi into the lachrymal sac. The drug containing tear fluid is carried from the lachrymal sac into the nasolacrimal duct and the drug gets absorbed here reaching the bloodstream. This absorption leads to drug wastage and more importantly, the presence of certain drugs in the bloodstream leads to undesirable side effects. For example, beta-blockers such as Timolol that is used in the treatment of wide-angle glaucoma have a deleterious effect on heart. Furthermore, application of ophthalmic drugs as drops results in a rapid variation in drug delivery rates to the cornea that limits the efficacy of therapeutic systems. Thus, there is a need for new ophthalmic drug delivery systems that increase the residence time of the drug in the eye, thereby reducing wastage and eliminating side effects.

In this article, we are propose to develop disposable soft contact lenses as a new vehicle for ophthalmic drug delivery to reduce drug loss, eliminate systemic side effects, and improve drug efficacy. The essential idea is to encapsulate the ophthalmic drug formulations in nanoparticles and to disperse these drug-laden particles in the contact lens matrix (Figure 1). If the nanoparticle size and loading are sufficiently low, the particle-loaded lens is transparent. In this project we focus on soft hydrogel lenses that are made of poly 2- hydroxyethyl methacrylate (HEMA). The p-HEMA hydrogel matrix is synthesized by bulk or solution free radical polymerization of HEMA monomers in presence of a cross linker. Addition of drug-laden particles in the polymerizing medium results in the formation of a particle-dispersion in the hydrogel matrix. If contact lenses made of this material are placed on the eye, the drug diffuses from the particles, travels through the lens matrix, and enters the post-lens tear film (POLTF), i.e., the thin tear film trapped in between the cornea and the lens. In the presence of a lens, drug molecules will have a much longer residence time in the post-lens tear film, compared to about 2 minutes in the case of topical application as drops. The longer residence time results in higher drug flux through the cornea and reduces the drug inflow into the mucous membranes, thus preventing drug absorption into the blood stream. In addition, due to the slow diffusion of the drug molecules through the particles and the lens matrix, drug-laden contact lenses can provide continuous drug release for extended periods of time.

* How new is this work and how does it differ from that of others who may be doing similar research?

Three groups in the past have attempted using soft contact lenses for drug delivery. They either soaked them in drug for some period of time or entrapped the drug inside a hollow cavity by bonding two separate pieces of lens material. Contact lenses soaked in drug solutions are not very effective at delivering medications for extended periods of time. Our proposal is significantly different as we are entrapping the drug molecules inside nanoparticles and incorporating them inside the lens matrix during the polymerization. This allows us greater flexibility in designing controlled ophthalmic drug delivery vehicles that can be tailored to various drug formulations, and that are effective for extended periods of time.

Recently, Graziacascone et al published a study on encapsulating lipophilic drugs inside nanoparticles, and entrapping the particles in hydrogels. They used PVA hydrogels as hydrophilic matrices for the release of lipophilic drugs loaded in PLGA particles. They compared the drug release from hydrogels with rates from the particles and found comparable results. However, there is no study available in literature that focuses on incorporating drug-laden nanoparticles in a p-HEMA contact lens matrix.

Figure 1.1: Schematic of the novel particle laden lens inserted in the eye

* Corresponding author's name and business title or position:

Anuj Chauhan, Assistant Professor

* Work department: Chemical Engineering Department

* Business address including organization: University of Florida, Chemical Engineering Department, Room 237 CHE PO Box 116005