New Technologies in Drug Delivery
Ongoing research approaches for contact lens (CL) drug delivery systems focus on improving the residence time of the drug at the surface of the eye to enhance bioavailability and to provide more convenient and efficacious therapy. Various techniques are used to incorporate the drug into the CL body, including
soaking the CL in drug solution
incorporating monomers able to interact with target drugs into the CL hydrogels
incorporating drug-loaded colloidal nanoparticles into the matrix of the CL
using a molecular imprinting technique in which the components of the hydrogel network are organized such that high-affinity binding sites for the drug are created
These CL delivery systems need to be designed so that they also preserve the transparency required for vision and the oxygen permeability necessary for corneal health. One way to maintain transparency is by lathing the encapsulated drug-polymer film in the periphery of the CL hydrogel.
Punctal plug–mediated delivery
Various punctal plug–mediated drug delivery systems are currently under clinical investigation. The design of these delivery systems generally includes a cylindrical polymeric core loaded with the drug compound, an impermeable shell, and a cap (or head portion of the plug exposed to the tear film) with pores from which the drug is released by diffusion. Most examples of punctal plug systems show nearly constant drug-release rates for drug molecules. Delivery of drugs by punctal plug has several potential advantages over administration via eyedrops, including lack of exposure to preservatives, dose reduction, controlled release of the drug at an optimum rate, and improved patient compliance. Limitations include ocular irritation, itching, discomfort, increased lacrimation, and spontaneous extrusion of the plug.
Gel-forming drops use pentablock copolymers as a vehicle for topical drug delivery. The drug is added to a nonviscous polymer drop. After the drop is in contact with the surface of the eye, the drop reacts upon exposure to body temperature and transforms into a gel.
Encapsulated cell technology
Encapsulated cell technology has been applied to the delivery of therapeutic agents for treatment of retinal diseases. This technology involves encapsulation of cells within a semipermeable polymer capsule that secretes therapeutic material into the vitreous. The device is implanted in the vitreous cavity and secured to the sclera.
Liposomes are synthetic lipid microspheres that serve as multipurpose vehicles for the topical delivery of drugs, genetic material, and cosmetics. They are produced when phospholipid molecules interact to form a bilayer lipid membrane in an aqueous environment. The interior of the bilayer consists of the hydrophobic fatty-acid tails of the phospholipid molecule, whereas the outer layer is composed of hydrophilic polar-head groups of the molecule. A water-soluble drug can be dissolved in the aqueous phase of the interior compartment; a hydrophobic drug can be intercalated into the lipid bilayer itself. However, the routine use of liposome formulation for topical ocular drug delivery is limited by the short shelf life of these products, their limited drug-loading capacity, and difficulty with stabilizing the preparation.
Nanotechnology has been increasingly applied in medication design to protect active molecules and provide sustained drug delivery. Methods for transporting hydrophilic and lipophilic drugs and genes include the use of biodegradable nanoparticles such as nanospheres, nanocapsules, and nanomicelles; the colloidal dispersion of nanoparticles as nanosuspension; and the use of nanoemulsion. These methods are modeled after the molecular structure of viruses.
The physical process of moving charged molecules by an electrical current is called iontophoresis. This procedure places a relatively high concentration of a drug locally, where it can achieve maximum benefit with little waste or systemic absorption. Animal studies have demonstrated that iontophoresis increases penetration of various antibiotics and antiviral drugs across ocular surfaces into the cornea and the interior of the eye. However, patient discomfort, ocular tissue damage, and necrosis restrict the widespread use of this mode of drug delivery.
Drug delivery devices based on microelectromechanical systems (MEMS) are under investigation to provide antiangiogenic therapy for age-related macular degeneration and steroid therapy for chronic uveitis. These devices are implanted in a manner similar to that used for current glaucoma tube shunts and deliver multiple microdoses of a drug directly into the vitreous cavity through a pars plana cannula. The device contains a drug reservoir with a refill port, a battery, electronics, and an electrolysis chamber to deliver the desired dose.
Excerpted from BCSC 2020-2021 series: Section 2 - Fundamentals and Principles of Ophthalmology. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.