Review
Polymeric hydrogels for novel contact lens-based ophthalmic drug delivery systems: A review

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Abstract

Only about 5% of drugs administrated by eye drops are bioavailable, and currently eye drops account for more than 90% of all ophthalmic formulations. The bioavailability of ophthalmic drugs can be improved by a soft contact lens-based ophthalmic drug delivery system. Several polymeric hydrogels have been investigated for soft contact lens-based ophthalmic drug delivery systems: (i) polymeric hydrogels for conventional contact lens to absorb and release ophthalmic drugs; (ii) polymeric hydrogels for piggyback contact lens combining with a drug plate or drug solution; (iii) surface-modified polymeric hydrogels to immobilize drugs on the surface of contact lenses; (iv) polymeric hydrogels for inclusion of drugs in a colloidal structure dispersed in the lens; (v) ion ligand-containing polymeric hydrogels; (vi) molecularly imprinted polymeric hydrogels which provide the contact lens with a high affinity and selectivity for a given drug. Polymeric hydrogels for these contact lens-based ophthalmic drug delivery systems, their advantages and drawbacks are critically analyzed in this review.

Introduction

The success of the therapy of eye ailments with ophthalmic drugs strongly depends on achieving sufficient drug concentration on the cornea for a sufficient period of time, but the typical delivery of drugs by eye drops which currently account for more than 90% of all ophthalmic formulations is very inefficient and in some instances leads to serious side effects [1], [2], [3]. Upon instillation in the eye, the drug mixes with the fluid present in the tear film and has a short residence time of approximately 2 min in the film. Only about 5% of the drug is absorbed into the cornea and the remaining either gets absorbed in the conjunctiva or flows through the upper and the lower canaliculi into the lacrimal sac [4], [5]. The drug containing tear fluid is carried from the lacrimal sac into the nasolacrimal duct. The nasolacrimal duct empties into the nasal cavity, where the drug is then absorbed into the bloodstream. This absorption leads to drug wastage, and more importantly, the presence of certain drugs in the bloodstream leads to undesirable side effects. Furthermore, the application of ophthalmic drugs by eye drops results in a rapid variation in the drug delivery rates to the cornea and this limits the efficacy of the therapeutic system [6], [7]. In addition, dosage through eye drops is inconsistent and difficult to regulate, as most of the drug is released in an initial burst of concentration [8], [9]. To increase the residence time of the drug in the eye, thereby reducing wastage and minimizing side effects, a number of researchers have proposed using contact lenses for ophthalmic drug delivery. It has been shown that in the presence of a lens, ophthalmic drugs have a much longer residence time in the post-lens tear film, compared with 2 min in the case of topical application as eye drops [10], [11], [12], [13]. The longer residence time will result in higher drug flux through the cornea and reduce the drug inflow into the nasolacrimal sac, thus reducing drug absorption into the bloodstream. Several methods have been proposed to make ophthalmic drugs deliverable by soft contact lens. In this review, the advantages and drawbacks of polymeric hydrogels for novel contact lens-based ophthalmic drug delivery systems are critically analyzed.

Section snippets

Polymeric hydrogels for conventional contact lens to absorb and release ophthalmic drugs

Conventional soft contact lenses have the ability to absorb a number of drugs when the lenses are pre-soaked in the drug solution, subsequently releasing them into the post-lens lacrimal fluid. As an alternative, one can also insert conventional soft contact lenses into eyes then apply eye drops. By this means, drugs can be absorbed and released by the soft contact lens, minimizing clearance and sorption through the conjunctiva [13], [14], [15], [16]. Several polymeric hydrogels have been

Polymeric hydrogels for piggyback contact lens combining with a drug plate or drug solution

Another method to make ophthalmic drugs deliverable by soft contact lens, involves incorporating the drug solution or drug plate in a hollow cavity made by bonding two separate pieces of lens material [27], [28]. Bourlais et al. [29] created “Drug plates” (8.0 mm diameter, 0.2 mm thickness, and 7.5 mm base curve) by freeze drying a mixture of levofloxacin (fluoroquinolon antibiotic) (20, 30, and 40 wt.%) and PVA, coated with a block styrene-(ethyl/butene)-styrene (SEBS) polymer solution (5.0, 7.5,

Surface-modified polymeric hydrogels to immobilize drugs on the surface of contact lenses

Surface-modified polymer hydrogels have been investigated with the aim of immobilizing ophthalmic drugs onto the surface of commercial disposable soft contact lenses and making them deliverable to treat eye disease [30], the immobilization process of ophthalmic drugs on the surface-modified soft contact lens is shown in Fig. 3. In the first step, polyethylenimine was covalently bounded onto the hydroxyl groups available on the surface of a commercial contact lens (Hioxifilcon B), followed by

Polymeric hydrogels for inclusion of drugs in a colloidal structure dispersed in the lens

Researchers have been dispersing micro-emulsion drops of ophthalmic drugs into soft contact lenses to treat eye ailments [31], [32], [33], [34]. First, ophthalmic drug formulations have been encapsulated in dimyristoyl phosphatidylcholine (DMPC) liposomes, and the drug-laden liposomes were dispersed in the lens material. If the nanoparticle size and loading are sufficiently low (the exact value depends on the refractive index mismatch between the gel and the particles), the particle-loaded lens

Ion ligand-containing polymeric hydrogels

Ion ligand-containing polymer hydrogels have been synthesized for a contact lens-based ophthalmic drug delivery system. Ionized ophthalmic drugs were bound in the soft contact lenses through ion ligands, and released into tear fluid by ion exchange. Hydrogels containing cationic functional groups in their side chain were investigated by copolymerization of methacrylamide propyltrimethylammonium chloride (MAPTAC) and HEMA (chemical structures of the model drug and monomers for cationic ion

Molecularly imprinted polymeric hydrogels

Molecularly imprinted polymer hydrogels were recently investigated biomaterials for contact lens-based ophthalmic drug delivery systems. In general, the preparation of molecularly imprinted polymers involves the self-assembly of functional monomers and target molecules, followed by polymerization with cross-linker in the presence of an inert solvent as a porogen. Upon removal of the target molecules, cavities that can recognize the spatial features and bonding preferences of the target

Perspectives

Currently worldwide, approximately 100 million people are estimated to be wearing contact lenses, and the number is increasing exponentially [44]. Although the main use of contact lenses is for correcting ametropia problems, they also hold interest as therapeutic devices for delivery of ophthalmic drugs. An ideal soft contact lens-based ophthalmic drug delivery system would exhibit (i) improved maximum drug loading property for extended delivery period; (ii) controllable zero-order release

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