Ophthalmic drug administration

Two of the largest challenges faced when using topicals to treat pathological states of the eye include patient compliance and ineffective absorbance of drugs into the cornea due to short contact times, solution drainage, tears turnover, and dilution or lacrimation. In fact, researchers in this field of drug delivery agree that less than 7% of drugs delivered to the eye reach and penetrate the corneal barrier, therefore, increasing the frequency of dosing used for topicals. Besides the logistical problems associated with using topicals, there are also systemic side effects which result from the administration of some drugs used to combat the pathological states of the eye. With the increased concentration of drugs in topicals and the frequent application to the eye, a majority of the drug is drained from the eye via nasolacrimal drainage. This drainage is thought to be the reason that systemic side effects exist from such administration. == Contact lenses as delivery devices ==

The U.S. Centers for Disease Control and Prevention (CDC) claims that there were "about 41 million contact lens wearers greater than 18 years old in the United States" in 2018. Of all of these wearers, nearly 90% of them wear contact lenses known as 'soft contact lenses' (SCLs). The main approaches that researchers in this field are using today are: molecular imprinting, supercritical soaking, solvent impregnation, and nanoparticle loading. The molecular structures of each of these drugs are shown below in the index of important scientific terminology. Supercritical soaking/solvent impregnation The supercritical soaking method is commonly used in hydrogel-based contact lenses and is the most common of all types of molecular drug loading techniques. Since this technique requires no special equipment or advanced knowledge of polymer-based hydrogels it is the least complex of all loading types. In order to load the hydrogel matrix with a certain drug, contact lenses are simply placed in a solution of the drug and the drug diffuses into the matrix. Since this loading technique is driven solely by the gradient of the drug concentration surrounding the lens relative to the hydrogel matrix, the diffusion rate and amount of drug that is loaded can be controlled solely by the concentration of the drug solution. Since this process allows for specific amounts of a certain drug to be loaded to the hydrogel matrix, this method of loading has become important for patient-specific (personalized) medicine and treatments. Nanoparticle loading The nanoparticle loading technique includes two major parts. The first part of this process is the creation and conjugation of a specific drug into or onto a nanoparticle or other colloidal particle. Next, the nanoparticle is loaded into the hydrogel matrix of the contact lens. In this case, before the drug can diffuse out of the hydrogel matrix to reach the cornea, it must also diffuse or be released out of the nanoparticle. == Physical and chemical challenges of loading ==

It is important to recognize the positives and negatives associated with each type of drug loading for using contact lenses as drug delivery devices. In order to seriously address the possibility of clinical translation of these devices, it is important to recognize the physical and chemical barriers. By understanding this better, the mechanism of drug loading and the controlled and sustained release of drugs to a patient's eye can be optimized. Lens transparency Since contact lenses are used on a part of the body that is important for normal daily functioning (sight) it is critical that scientists take into account the transparency of the lens. Cells, being the basic component of living organisms, require sustained and constant access to oxygen in order to survive. The cornea of the eye is not supplied with blood as are most other cells in the body, making this a challenging part of the body to which to deliver drugs. Silicon-base contact lenses have also been shown to have some other very important physical parameters. This could be due to the water acting as a lubricant to some drugs and allowing the drug to be more easily facilitated into the matrix. This would essentially allow for more drug to be loaded into contact lenses of this type. Drug release kinetics The most important factor that must be taken into account when designing any type of drug delivery device, and specifically ocular devices, is the release rate of a drug. As discussed previously, the deliver rate and kinetics associated with drugs to the eye can reach levels that are toxic to the eye or could even cause undesirable side effects. The rate of release of a drug is also important because too slow of a release could have no beneficial outcome for the patient and a release that is too quick could result in negative side effects. Thus, it is important to balance the factors that govern the release of drugs from contact lenses as potential drug delivery devices. Researchers such as C. Alvarez-Lorenzo have tested (with animal models) and have data which supports that molecularly imprinted contact lenses release drugs in a sustained and long period of time. It has also been supported by researchers that the rate of drug release can be controlled by incorporating vitamin E within the hydrogen matrix. Systemic side effects Over time, it has been reported that many of the same drugs and eye drops used to treat particular eye diseases do, in fact, result in systemic side effects that could possibly be minimized or limited due to a slower, more sustained release of the drug. The systemic side effects of glaucoma medications such as latanoprost increased heart rate resulting in cardiac arrhythmias, bronchoconstriction, and hypotension. These complications could be life-threatening. Some other drugs that help to reduce the effects of glaucoma in the eye result in vomiting, diarrhea, tachycardia and bronchospasm. It has been found that some drugs delivered in the form of eye drops are highly toxic to children since their total body volume and tissue volumes are much lower than that of an adult for which the drugs are intended for use. In this case, some parents are not aware of these implications and could use the same drug they would use to help treat their children's bacterial infections in the eye. Moreover, some drugs administered to the eye have been shown to result in cardiac depression and propagation of some disorders such as asthma. With continued research in this area, it has become known that skin irritation, itching or rash are commonly associated with drugs used to treat ocular bacterial infections. == Ocular disorders ==

There are currently four main ocular disorders that have been heavily investigated and have shown success with using contact lenses as possible devices for molecular drug delivery. Bacterial infection The drug release rate is extremely important in treating many diseased states of the eye, bacterial infections being one of them. Ciprofloxacin and norfloxacin are drugs that are normally used to treat bacterial infections of the eye. It is of utmost importance that these drugs stay in the therapeutic window for an extended period of time in order to be fully effective and kill bacteria. A poly(lactic-co-glycolic acid)-based contact lens was shown to release latanoprost at a sustained release rate of up to a month in animal models by Ciolino et al. at Harvard Medical School and Massachusetts Institute of Technology. Latanoprost is one of the drug interventions used to treat patients with glaucoma, generally in the form of topicals such as eye drops. Dry eye More than 50% of all contact lens wearers report that they experience dry eye. In order to help combat this issue and be assured that this does not occur in people that will one day be using drug eluting contact lenses, it is important to make sure that this complication is highly investigated. However, these investigations will not only be beneficial for contact lenses as drug delivery devices, but it will also have positive implications on contact lens wearers who use lenses for vision correction and appearance. ==References==