Challenges and innovations in ocular drug delivery methods

  Claus Cursiefen A wide range of new and emerging drug delivery systems offer the potential to improve therapeutic efficacy, enhance patient comfort and compliance and reduce side-effects in the treatment of a wide range of ocular conditions. So delegates were told at yesterday’s clinical research symposium on drug delivery systems. Chaired by Jesper Hjortdal and Rudy MMA Nuijts, the symposium “When Surgery is Not Enough: New Drug Delivery Methods” provided a broad overview of innovations in the field of drug delivery and highlighted varied approaches to the challenge of attaining optimal and sustained therapeutic effect in the eye.   HAEMATIC DERIVATIVES Jesús Merayo Lloves MD from Spain opened the symposium with a presentation on the potential of haematic derivatives to treat a wide range of ocular surface diseases. He explained that platelet-rich plasma (PRP) derivates work by supplying fundamental factors to maintain the integrity of the ocular surface. Current PRP preparation methods are highly variable and yield a range of products including plasma rich in growth factors (PRGF), which is particularly interesting for ophthalmic applications. “Early studies and our own clinical experience to date have shown the effectiveness of PRGF in the management of patients with severe or moderate dry eye disease. However, it will probably prove of most benefit in patients with neurotrophic dry eye, dry eye post-LASIK or post-keratoplasty and graft versus host disease (GVHD),” he said. The possibility of pre-treating vascularised corneas prior to transplantation was discussed by Claus Cursiefen MD, PhD, from Germany. He told the audience that some new approaches under investigation, both pharmacological and mechanical, may prove effective in reducing the rejection rate after keratoplasty surgery. Options are already available to target immature blood and lymphatic vessels by using topical steroids such as prednisolone, or topical or subconjunctival anti-VEGF agents, he said. For mature blood vessels, a mechanical technique such as fine-needle cautery combined with anti-VEGF medications shows promise. Other experimental approaches to target mature lymphatic vessels include photodynamic therapy (PDT) or corneal crosslinking.   COMBINATION APPROACH Turning to the rich potential of nanomaterials to deliver effective drug delivery to ocular tissues, Quirina Ferreira MD from Portugal shared her research on a novel combination approach to treating glaucoma. This is focused on the possibility of using nanostructured films as a delivery vehicle for brimonidine to treat glaucoma. “The layer-by-layer films are able to release precise amounts of brimonidine to the biological environment at specific periods of time. In addition to glaucoma, these nanostructured films may be used with other ocular drugs and can be coated in any type of surface or ocular device,” she said. In vitro and in vivo trials are needed to validate the films’ efficiency in the ocular environment, she said. The potential of nanoparticles to effect a paradigm shift in drug delivery methods was also underscored by Einar Stefánsson MD, PhD, who presented the latest data on cyclodextrin as a novel eye-drop technology. Cyclodextrin nanoparticle suspension in eye drops increases solubility and provides sustained release of the drug. “This is particularly interesting because these drops can deliver drugs to the retina in pharmacologically significant concentration,” he said. Other potential applications include diabetic macular oedema and intermediate uveitis with cystoid macular oedema. Marc Labetoulle MD from France gave his talk on the possibility of performing drop-less cataract surgery using Mydrane (Théa Laboratories), which combines two mydriatics and one anaesthetic in a single-use ampoule. He said that Mydrane induces rapid and stable mydriasis, has a good safety profile and is more comfortable for the patient compared to conventional eye drops. The symposium was rounded off with a presentation from Scheffer Tseng MD, PhD, who discussed the clinical applications of amniotic membrane ring and derivatives to promote corneal nerve regeneration and treat dry eye.