Use of nanotechnology to deliver topical ophthalmic medications
Topical drug delivery systems are widely used in transdermal, mucous membrane, ophthalmic, and otic applications as they are highly versatile, effective, and convenient. However, medication delivery complications such as drug solubility, bioavailability, timed release, and inaccurate physical targeting do exist. Recent advancements in nanotechnology are being utilized in these systems to improve topical drug therapies.
Topical drug delivery plays an important role in current drug treatments. Topical applications are simple, effective, noninvasive, and tend to correlate with high patient compliance due to easy self-administration and lack of side effects. Topical administration is beneficial as systemic side effects and first pass metabolism are avoided, and medications can be applied directly to the site of interest. Topical delivery is especially beneficial for small lipophilic and concentrated drugs. A broad range of topical delivery formulations are currently being used. Despite the benefits and frequency of topical applications, several challenges to delivery persist, including properties of the physical delivery site, properties of the delivery formulation, and properties of the drug to be applied.
Nanoparticles are particularly suited to aid in topical drug delivery as they are able to navigate multiple biobarriers. Nanomaterials possess properties that allow them to interact at drug delivery sites in controlled and specific ways due to characteristics like high specific surface area, adjustable reactivity, and controllable surface chemistry. This is favorable as they are thus able to move across multiple types of cell membranes, tissues, and organs in order to target specific cells or subcellular tissue in spatially and time-controlled ways. Drugs can be attached to these particles by adsorption, encapsulation, or other methods and so gain expanded capacities for solubility, therapeutic index and duration of activity. Nanoparticle delivery systems unload drugs by their own erosion or by cued responses to their environment such as pH, temperature, ultrasound, light, and magnetic fields. The biophysical composition of each nanomaterial is unique and can be adapted to suit the drug and delivery site of interest. Some examples of useful nanodelivery device structures are liposomes, polymersomes, solid lipid nanoparticles, nanofiber mats, and nanoneedles.
As reported in Advanced Therapeutics, the eyes are a frequent target for topical drug applications, and all forms of treatment could benefit from improved length of duration, decreased invasiveness, and enhanced patient comfort. Various types of ocular drug formulations are used to treat different physical areas in the ocular space. The front of the eye (including the cornea, conjunctiva, trabecular meshwork, iris, and ciliary body) is treated with topical or injectable subconjunctival medications. The back of the eye refers to the space from the lens to the retina and is treated by injections into the vitreous space. Important key elements of all ocular drug formulations are bioavailability, dosing frequency, drug elimination, and stability.
The anatomy of the eyes provides many complications to successful ocular drug delivery. Most drug administration to the front of the eye occurs via topical eye drops, emulsions, and suspensions which interact at the surface of the eye with lacrimal fluid. Lacrimal film lubricates and protects the cornea and conjunctiva, and is composed of a mucus, aqueous, and lipid layer.
The cornea is composed of the external epithelium, Bowman’s membrane, stroma, Descement’s membrane, and inner endothelium. The conjunctiva is made of an external epithelium and a connective stroma. The conjunctiva covers the anterior sclera and lines the inside of the eyelids. Drugs are able to reach the trabecular meshwork, iris, or ciliary body via the cornea and conjunctiva. The tight junctions of external epithelial cells of the cornea are the strongest limitation to topical absorption of ophthalmic formulations.
Once a medication does reach the conjunctiva, a prevalence of blood and lymph vessels aid in the quick clearance of the drug from the site. Blood circulation also contributes to limited systemic absorption of drug when blinking, increasing the chances of medication side effects. Metabolic enzymes, such as lysozyme, in the lacrimal fluid also degrade medications at the ocular surface. The result of these challenges to topical applications is a very small percentage of the active drug remains available for use before being degraded or cleared from the ocular site. The obvious outcomes of rapid drug removal are loss of efficacy, increased dosing and drug concentrations, and decreased patient adherence to therapy. Attempts to mediate these obstacles include small lipophilic and hydrophilic formulations to improve permeability as well as large viscous formulations and well as soft contact lenses and even blocking of the lacrimal ducts to slow draining and so increase time of action at the eye.
Nanoparticle formulations show large promise in this area as particle sizes can be designed less than ten um which avoids eye irritation and excessive tear production. Nanoformulations such as nanomicelles, nanowafers, and nanoneedles can be used for organic and inorganic delivery to the eye. Nanoparticles are also used successfully in combination with contact lenses and viscous agents to increase retention time at the eye. Contact lenses soaked with nanoparticle drugs are of special interest due to the long length of daily wear by the patient. Subconjunctival ocular injections are obviously a last choice due to their invasive nature and the specialized administration by a healthcare provider that are required.
However, nano-based subconjunctival injections are currently being studied for vision spectrum enhancing retinal treatments as these therapies can reach the posterior eye.
Injectable treatments to the vitreous humor of the posterior space are used to amend the devastating vision loss of disorders such as macular degeneration, diabetic retinopathy, and diabetic macular edema. Much like subconjunctival injections, these speciality-only therapies are invasive, expensive, frequent, and substantially increase the risk of bleeding, infections, or cataracts. Medications with a large particle size have been used to increase the length of therapy in these patients, but the large particles cause visual disturbances due to light scattering. Nanomaterials are being developed that can possess a longer length of action and not adversely affect vision. Charged nanomedications can also be used to more specifically target the retina and avoid loss in the vitreous space. Longer-term implant nanoinjectable medications are also currently being explored that can deliver drugs from the vitreal area for several months or years.
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