Biomimetic contact lenses eluting olopatadine for allergic conjunctivitis.

UNLABELLED: Combination of the ability of contact lenses (CLs) to act as a physical barrier against airborne antigen and to serve as a sustained depot of antihistaminic drugs may improve the efficiency of treatments of some ocular allergic diseases. The aim of this work was to develop CLs that exhibit affinity to olopatadine by mimicking the composition of the natural H1-receptor for which olopatadine behaves as a selective antagonist. Functional monomers that match the chemical groups of the receptor and application of the molecular imprinting technology led to hydrogels able to load high amounts of olopatadine and to sustain the release once in contact with lachrymal fluid. Optimized hydrogels prepared with acrylic acid, 2-acrylamido-2-methyl-1-propanesulfonic acid and benzylmethacrylate as functional monomers provided in few hours olopatadine concentrations similar to those of commercially available eye drops but the levels could be sustained for a whole day, demonstrating their efficacy. Olopatadine-loaded CLs successfully passed the HET-CAM test of ocular irritancy and showed good compatibility with mast cells. They were able to inhibit the release of histamine and TNF-α from sensitized mast cells, proving their potential application in preventing and treating allergic conjunctivitis. STATEMENT OF SIGNIFICANCE: Contact lenses (CLs) with affinity for antiallergic drugs may constitute an advantageous alternative to eye drops in management of ocular allergies for both contact lens wearers and patients who eventually use neutral CLs as therapeutic platforms. The present work represents a step forward in the state of the art of drug-CL combo products by (i) mimicking the composition of the human receptor of the drug, (ii) exploring combinations of functional monomers that include a monomer (2-acrylamido-2-methyl-1-propanesulfonic acid; AMPSA) with a strong acid group (pKa<4) able to enhance the interaction of the network with olopatadine in the saline environment of the lachrymal fluid, and (iii) analysing in detail the antihistamic effects provided by olopatadine released from the CLs on sensitized mast cells.

Soft contact lenses for controlled ocular delivery: 50 years in the making.

The use of contact lenses as ocular bandages for drug delivery was envisioned nearly 50 years ago by Wichterle and co-workers. Despite the therapeutic advantages that can be obtained, this application has to face up to the poor affinity shown by commercially available contact lenses for most ophthalmic drugs, resulting in small amounts of drug being loaded and short time of therapeutic levels in the eye structures. Novel strategies that appeared in the beginning of 21st century, for example coating lenses with vitamin E, incorporation of drug nanocarriers or application of molecular imprinting technology, are becoming relevant tools for development of true drug/contact lens combination products that may be available for ocular therapy in the foreseeable future.

Antifouling foldable acrylic IOLs loaded with norfloxacin by aqueous soaking and by supercritical carbon dioxide technology.

Cataracts treatment usually involves the extraction of the opaque crystalline lens and its replacement by an intraocular lens (IOL). A serious complication is the occurrence of endophthalmitis, a post-surgery infection mainly caused by Staphylococcus epidermidis, Staphylococcus aureus, and Pseudomonas aeruginosa. IOLs having the ability to load and to release norfloxacin in a controlled way and at efficient therapeutic levels may help to overcome these issues. In this work, acrylic hydrogels combining 2-hydroxyethyl methacrylate (HEMA) and 2-butoxyethyl methacrylate (BEM) at various ratios were prepared to attain biocompatible networks that can be foldable even in the dry state and thus insertable through minor ocular incision, and that load therapeutic amounts of norfloxacin. Acrylamide (AAm) and methacrylic acid (MAAc) were also incorporated as functional comonomers in small proportions. Water sorption, contact angle, protein adsorption, and optical properties of the networks were characterized. BEM notably decreased the T(g) of the networks, but also the loading by immersion in aqueous solution (presoaking). Then, a scCO(2)-based impregnation/deposition (SSI) method was implemented to improve the uptake of the drug. Loading capacities were discussed in terms of the comonomers composition and the employed method and operational conditions. The networks prepared with HEMA/BEM 20:80 vol/vol and processed with supercritical fluids combine adequate mechanical properties, biocompatibility and norfloxacin loading/release, and seem to be suitable for developing norfloxacin-eluting IOLs.

Drug-Eluting Intraocular Lenses.

Notable advances in materials science and in surgical techniques make the management of cataract by replacement of the opaque crystalline with an intraocular lens (IOL), one of the most cost-effective interventions in current healthcare. The usefulness and safety of IOLs can be enhanced if they are endowed with the ability to load and to sustain drug release in the implantation site. Drug-eluting IOLs can prevent infections and untoward reactions of eye tissues (which lead to opacification) and also can act as drug depots for treatment of several other ocular pathologies. Such a myriad of therapeutic possibilities has prompted the design of drug-IOL combination products. Several approaches are under study, namely combination of the IOL with an insert in a single device, soaking in drug solutions, impregnation using supercritical fluids, coating with drug/polymer layers, and covalent grafting of the drug. The advantages/limitations of each technique are discussed in the present review on selected examples. Although more in vivo data are required, the information already available proves the interest of some approaches in ocular therapeutics.