Novel contact lenses provide extended pain relief to laser eye surgery patients

Anuj Chauhan and colleagues explain that more than 1 million laser eye correction procedures are performed each year in the U.S. The surgery enables most patients to see clearly without eye glasses or contact lenses. The procedure known as LASIK is the most common type of laser eye surgery, but complications can develop if the patient undergoes trauma or is hit very hard at any time after the procedure. Photorefractive keratectomy (PRK) doesn't have this complication, and that's why it is preferred for athletes and those in the military. A downside to PRK, however, is a longer period of pain after surgery. To ease their pain, PRK patients place drops of several medications, including anesthetics, into their eyes every few hours, which can interfere with daily life and increase the risk of drug overdose. PRK patients receive a special "bandage contact lens" after surgery to help the outer layer of the eye heal.

The researchers tested whether anesthetics loaded onto this type of lens could release the drugs over time automatically. They found that adding vitamin E to the lenses extended the time of release of three commonly used anesthetics from just under two hours to up to an entire day — or a few days in some instances. The vitamin E acts as a barrier, keeping the anesthetics on the eye, right where they are needed. The researchers say that, in the future, these lenses could serve as bandage contact lenses after PRK surgery while also delivering necessary pain medications.

More information: Transport of Topical Anesthetics in Vitamin E Loaded Silicone Hydrogel Contact Lenses, Langmuir, 2012, 28 (2), pp 1478–1487. DOI: 10.1021/la203606z

Abstract
Transport of surface active anesthetic drugs through silicone hydrogel contact lenses containing nanosized vitamin E aggregates is explored for achieving extended anesthetics delivery. Commercial silicone hydrogel contact lenses release most ophthalmic drugs including local anesthetics for only a few hours, which is not adequate. Here we focus on creating dispersion of highly hydrophobic vitamin E aggregates in the lenses as barriers for drug diffusion for increasing the release durations. This approach has been shown previously to be successful in extending the release durations for some common hydrophilic ophthalmic drugs. The topical anesthetic drugs considered here (lidocaine, bupivacaine, and tetracaine) are hydrophilic at physiologic pH due to the charge, and so these cannot partition into the vitamin E barriers. However, these surface active drug molecules adsorb on the surface of the vitamin E barriers and diffuse along the surface, leading to only a small decrease in the effective diffusivity compared to non-surface-active hydrophilic drugs. The drug adsorption can be described by the Langmuir isotherm, and measurements of surface coverage of the drugs on the vitamin E provide an estimate of the available surface area of vitamin E, which can then be utilized to estimate the size of the aggregates. A diffusion controlled transport model that includes surface diffusion along the vitamin E aggregates and diffusion in the gel fit the transport data well. In conclusion, the vitamin E loaded silicone contact lens can provide continuous anesthetics release for about 1–7 days, depending on the method of drug loading in the lenses, and thus could be very useful for postoperative pain control after corneal surgery such as the photorefractive keratectomy (PRK) procedure for vision correction.

Provided by American Chemical Society (news : web)

Understanding how glasses 'relax' provides some relief for manufacturers

 Researchers at the National Institute of Standards and Technology and Wesleyan University have used computer simulations to gain basic insights into a fundamental problem in material science related to glass-forming materials, offering a precise mathematical and physical description of the way temperature affects the rate of flow in this broad class of materials -- a long-standing goal.

Manufacturers who design new materials often struggle to understand viscous liquids at a molecular scale. Many substances including polymers and biological materials change upon cooling from a watery state at elevated temperatures to a tar-like consistency at intermediate temperatures, then become a solid "glass" similar to hard candy at lower temperatures. Scientists have long sought a molecular-level description of this theoretically mysterious, yet common, "glass transition" process as an alternative to expensive and time-consuming trial-and-error material discovery methods. Such a description might permit the better design of plastics and containers that could lengthen the shelf life of food and drugs.

A fundamental question is why many materials behave differently when temperature changes. In some "fragile" glass-forming materials, a modest variation in temperature can make the material change from highly fluid to extremely viscous, while in "strong" fluids this change in viscosity is much more gradual. This effect influences how long a manufacturer has to work with a material as it cools. "For decades, material scientists have heavily relied on empirical rules of thumb to characterize these materials," says NIST theoretician Jack Douglas. "But if you want to design a material that does precisely what you want, you need a molecular understanding of the underlying physical processes involved."

According to Douglas, the increasingly viscous nature of glass-forming liquids is related to molecules that move together in long strings around other atoms that are almost frozen in their motion. The growth of these snake-like structures leads to an increase in the viscosity of the liquid: the lower the temperature, the longer the chains, and the more viscous the fluid. The team found that the rate at which these spontaneously organizing snake-like strings grow in size as the material cools is quantitatively related mathematically to the fluid fragility -- confirming intuitive arguments made nearly half a century ago by physicists G. Adams and J.H. Gibbs, but now bolstering them with a firm computational underpinning.

Douglas and his collaborator Francis Starr of Wesleyan University achieved a large variation of fluid fragility through use of a computer model, which mimics a polymer fluid that includes tiny nanometer-sized particles. Portraying the addition of various amounts of nanoparticles and varying their interaction with the polymers, Starr says, gave the team a sort of "knob to tweak" to reveal how the fluidity changed with temperature and how the motion of the clusters was quantitatively related to changes in the fluid's properties. This tuning of cooperative motion in glass-forming liquids and fragility should be crucial in material design. Douglas says.

Story Source:

The above story is reprinted (with editorial adaptations by ScienceDaily staff) from materials provided by National Institute of Standards and Technology (NIST).

Journal Reference:

Francis Starr, Jack Douglas. Modifying Fragility and Collective Motion in Polymer Melts with Nanoparticles. Physical Review Letters, 2011; 106 (11) DOI: 10.1103/PhysRevLett.106.115702

Injectable gel could spell relief for arthritis sufferers

Some 25 million people in the United States alone suffer from rheumatoid arthritis or its cousin osteoarthritis, diseases characterized by often debilitating pain in the joints. Now researchers at Brigham and Women's Hospital (BWH) report an injectable gel that could spell the future for treating these diseases and others.

Among its advantages, the gel could allow the targeted release of medicine at an affected joint, and could dispense that medicine on demand in response to enzymes associated with arthritic flare-ups.

"We think that this platform could be useful for multiple medical applications including the localized treatment of cancer, ocular disease, and cardiovascular disease," said Jeffrey Karp, leader of the research and co-director of the Center for Regenerative Therapeutics at BWH.

Karp will present the findings April 15 at the annual meeting of the Society for Biomaterials (SFB) as part of winning the coveted SFB Young Investigator Award for this work. The work was also reported by Karp and colleagues in the May 2011 issue of the Journal of Biomedical Materials Research (JBMR): Part A, and is currently available on the journal's website.

Local Delivery

Arthritis is a good example of a disease that attacks specific parts of the body. Conventional treatments for it, however, largely involve drugs taken orally. Not only do these take a while (often weeks) to exert their effects, they can have additional side effects. That is because the drug is dispersed throughout the body, not just at the affected joint. Further, high concentrations of the drug are necessary to deliver enough to the affected joint, which runs the risk of toxicity.

"There are many instances where we would like to deliver drugs to a specific location, but it's very challenging to do so without encountering major barriers," says Karp, who also holds appointments through Harvard Medical School (HMS), Harvard Stem Cell Institute (HSCI), and the Harvard-MIT Division of Health Sciences and Technology (HST).

For example, you could inject a drug into the target area, but it won't last long--only minutes to hours--because it is removed by the body's highly efficient lymphatic system. What about implantable drug-delivery devices? Most of these are composed of stiff materials that in a dynamic environment like a joint can rub and cause inflammation on their own. Further, most of these devices release medicine continuously--even when it's not needed. Arthritis, for example, occurs in cycles characterized by flare-ups then remission.

Toward the Holy Grail

"The Holy Grail of drug delivery is an autonomous system that [meters] the amount of drug released in response to a biological stimulus, ensuring that the drug is released only when needed at a therapeutically relevant concentration," Karp and colleagues write in JBMR. His coauthors are Praveen Kumar Vemula, Nathaniel Campbell, and Abdullah Syed of BWH, HMS and HSCI; Eric Boilard (now at Université Laval), Melaku Muluneh, and David Weitz of Harvard University; and David Lee of BWH, currently at Novartis. Karp notes the key involvement of Lee, a doctor who is "treating patients with the problem we're trying to solve."

The researchers tackled the problem by first determining the key criteria for a successful locally administered arthritis treatment. In addition to having the ability to release drug on demand, for example, the delivery vehicle should be injectable through a small needle and allow high concentrations of the drug. The team ultimately determined that an injectable gel seemed most promising.

Next step: what would the gel be made of? To cut the time involved in bringing a new technology to market, the team focused only on materials already designated by the Food and Drug Administration as being generally recognized as safe (GRAS) for use in humans.

Ultimately, they discovered a GRAS material that could be coaxed into self-assembling into a drug-containing gel. "The beauty of self-assembly is that whatever exists in solution during the assembly process--in this case, a drug--becomes entrapped," says Vemula, first author of the paper, who also has an appointment at HST.

They further expected that the same material would disassemble, releasing its drug payload, when exposed to the enzymes present during inflammations like those associated with arthritis.

Promising Results

A series of experiments confirmed this. For example, the team created a gel containing a dye as a stand-in for a drug, then exposed it to enzymes associated with arthritis. The drug was released. Further, the addition of agents that inhibited the enzymes stopped the release, indicating that the gel "can release encapsulated agents in an on-demand manner," the researchers write. Although the team has yet to test this in humans, they did find that dye was also released in response to synovial fluid taken from arthritic human joints.

Among other promising results, the researchers found that gel injected into the healthy joints of mice remained stable for at least two months. Further, the gel withstood wear and tear representative of conditions in a moving joint.

Additional tests in mice are underway. The technique has yet to be demonstrated in humans, but the researchers write that it "should have broad implications for the localized treatment of many…diseases" caused by the enzymatic destruction of tissues.

The researchers have applied for a patent on the work, which was sponsored by the Center for Integration of Medicine and Innovative Technology (CIMIT) through the U.S. Army and by the Harvard Catalyst Program.

Provided by Brigham and Women's Hospital