Critical role for drug delivery in the development of new ophthalmic treatments

Abstract

Future Medicinal ChemistryVol. 4, No. 17 EditorialFree AccessCritical role for drug delivery in the development of new ophthalmic treatmentsH SheardownH SheardownMcMaster University, Departments of Chemical Engineering & Pathology & Molecular Medicine, Hamilton, ON L8S 4L7, USA. Search for more papers by this authorEmail the corresponding author at sheardow@mcmaster.caPublished Online:29 Nov 2012https://doi.org/10.4155/fmc.12.161AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareShare onFacebookTwitterLinkedInRedditEmail Keywords: biomaterialscontact lensdrug deliveryin situ gelling polymermicroneedlesSince the first intraocular lenses were implanted more than 60 years ago, biomaterials have played a significant role in ophthalmic treatments. Today, cataract surgery is the most common, and among the most successful, surgical procedure available, contact lenses correct the vision of millions the world over and newer materials treatments, such as artificial corneas, have the potential to incorporate cells and restore the vision of patients whose sight has been compromised. Still, with the aging population, vision loss is becoming more prevalent and with this vision loss comes a higher incidence of depression, a greater risk of falls and injury, and in the elderly, earlier admission to a nursing home [1]. Significant therapeutic advances continue to be made for treating diseases such as age-related macular degeneration and diabetic retinopathy, which are currently the leading causes of blindness in the developed world among the aged and working age populations, respectively. However, delivery of these therapies to the target tissue remains a challenge. Therefore, likely the greatest future potential application of biomaterials in the eye and greatest opportunity for ophthalmic therapies lies in the ability to deliver these therapeutic agents to the eye in a controlled and sustained fashion.Polymeric delivery devices have become common in the treatment of a host of disease applications. However, the anatomical considerations of the eye make it a challenging location for a drug delivery system. Still, a recent PubMed search demonstrates significant interest. A search of ‘drug delivery’ and ‘eye’ resulted in 1120 papers between 2000 and 2009; the same search for 2010 to current day resulted in more than 500 hits.For delivery to the anterior segment, contact lens-based systems seem to have real potential. Treatment of challenging infections or even glaucoma may be possible with such a device. Development of a glaucoma treatment device would be particularly attractive given that it has been reported that the rate of patient compliance, while high immediately prior to an ophthalmologist visit and immediately following, has been reported to be as low as 20% [2]. Therefore, control of intraocular pressure is not being achieved with therapies that have the potential to be extremely effective.With the advent of silicone hydrogel lens materials, it is clinically possible for the lens to be worn for periods of up to 30 days, making this a potentially more attractive option for anterior segment drug delivery. Numerous studies have used commercially available contact lenses soaked in a drug of interest [3,4]. However, the results of these studies have demonstrated that more sustained release is necessary for clinical efficacy.Recently, a number of groups have shown extended release from contact lens materials. Ciolino et al. incorporated a degradable drug-containing component into conventional contact lens materials and demonstrated efficacious release for a period of more than 1 week [5,6]. Chauhan and colleagues have used various techniques to generate drug-containing contact lens materials. Particularly promising is the incorporation of an agent that increases tortuosity of the material to lengthen the release period [7–9]. The strength of these approaches is that they can be applied to various commercially available materials including conventional and silicone hydrogel lenses. Work in the author’s laboratory has shown that the presence of hyaluronic acid in model silicone hydrogel materials can also be used to control the release of drugs, particularly hydrophobic drugs [10]. Much of the focus of the work in the Byrne group has involved the use of molecular imprinting methods to incorporate a variety of drugs [11–13]. The results have shown that release from various types of materials is possible. Overall, there is significant promise for the use of contact lens materials to deliver drugs to the eye. However, it is necessary for the focus of future work to be extended-wear silicone hydrogel lenses, as delivery periods of 1 week or more are desirable and the need to remove the drug delivering contact lens on a nightly basis is unlikely to provide the therapeutic effect required.A considerably more challenging problem, but one with a potentially greater reward, is drug delivery to the posterior eye. The natural anatomic and physiologic limitations of the eye make this a particularly difficult target tissue. While injections into the back of the eye have revolutionized treatment of posterior segment eye disease, particularly age-related macular degeneration, problems remain. Each breach of the posterior eye carries with it a risk of complications including cataract, retinal detachment and endophthalmitis. Coupled with the need for frequent injections to maintain therapeutic drug levels in the eye, this treatment is amenable only to older patients with more advanced forms of age-related macular degeneration, leaving younger patients with other posterior segment diseases relatively untreated. Ongoing research into novel therapies for treating diseases such as dry age-related macular degeneration and diabetic retinopathy, are going to be hampered by the lack of ability to effectively maintain therapeutically relevant doses at the target tissue. The lack of effective drug-delivery systems will, ultimately, be the limiting factor in treating these diseases.The use of drug-delivery systems in the back of the eye is not without precedent, although adoption of these types of technologies has not been widespread despite the potential benefits. Of commercial devices, the Retisert® and Vitrisert® devices have experienced the most success. Of similar design, both are surgically implanted and, therefore, must ultimately be removed. More recently, the Ozurdex® device has been approved. Delivering corticosteroids to the back of the eye for the treatment of macular edema associated with retinal vein occlusion, these free-floating, bioerodible devices are put into place with a 22 gauge applicator that creates a self-sealing wound. The Iluvien™ device, currently still in the regulatory process in most locations, releases the steroid fluocinolineacetonide for periods of between 1.5 and 3 years with promising clinical results.There are also many promising delivery systems currently in the research phase. Transcleral permeation, nano- and micro-particles [14], microneedle-based systems [15,16] and novel injectable in situ gelable systems [17,18] all have promise to give long-term delivery of drugs in the back of the eye. Regardless of the system, delivery durations of at least 6 months would be essential for widespread adoption, with longer delivery durations being more desired. Degradability into clearable and nontoxic properties may also be useful. Furthermore, the ability for some sort of physician control may be a potentially desired property. Additional properties would likely be drug specific and will, therefore, depend on the nature of the pharmaceuticals currently under development and in testing. However, regardless of the nature of the pharmaceutical agent, successful delivery will ultimately be critical to the ability of newly developed pharmaceutical agents to successfully treat the condition of interest. Therefore, it is clear that partnerships between the drug manufacturers, drug-delivery researchers and physicians will be necessary to generate new and better therapies for the eye and that novel drug delivery methodologies will play an important role in future ophthalmic treatments.Financial & competing interests disclosureThe author has no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.No writing assistance was utilized in the production of this manuscript.References1 Bramley T, Peeples P, Walt JG, Juhasz M, Hansen JE. Impact of vision loss on costs and outcomes in medicare beneficiaries with glaucoma. Arch. 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Biomacromolecules11(9),2261–2267 (2010).Crossref, Medline, CAS, Google ScholarFiguresReferencesRelatedDetailsCited ByChitosan in Biomedical Engineering: A Critical ReviewCurrent Stem Cell Research & Therapy, Vol. 14, No. 2Drug Delivery: Localized and Systemic Therapeutic Strategies with Polymer Systems15 October 2018Drug Delivery: Localized and Systemic Therapeutic Strategies with Polymer Systems8 June 2019Keep your eyes open: challenges and opportunities in ophthalmic therapeuticsShusheng Wang29 November 2012 | Future Medicinal Chemistry, Vol. 4, No. 17 Vol. 4, No. 17 Follow us on social media for the latest updates Metrics History Published online 29 November 2012 Published in print November 2012 Information© Future Science LtdKeywordsbiomaterialscontact lensdrug deliveryin situ gelling polymermicroneedlesFinancial & competing interests disclosureThe author has no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.No writing assistance was utilized in the production of this manuscript.PDF download