NANOTECHNOLOGY

Marc Ramis Castelltort PhD

New nanotechnology 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, Marc Ramis Castelltort PhD told delegates attending the XXXIII Congress of the ESCRS in Barcelona, Spain.

“What we are trying to do in the nanotechnology field is to increase the level of selected molecules in a specific region to improve the payload efficacy of the drug and reduce related side effects. In most cases, we use a molecule that is able to target specific tissue. In oncology, for example, CD44 is a receptor expressed in different solid tumours, so we use nanoparticles that actively target CD44,” he said.

There is no gold standard nanoparticle for drug delivery systems, with each nanoparticle possessing specific physico-chemical properties that make them unique for a specific application, explained Dr Ramis Castelltort, CEO of Tech and Business Innovation, Spain.

“We cannot use a single particle for delivering any kind of drug or for any kind of clinical indication. Instead we have different families of nanomaterials that can be used in drug delivery such as inorganic, polymeric, solid lipid nanoparticles, nanocrystals, nanotubes, dendrimers, and so forth. Every year we see the emergence of new types of nanomaterials that could have potential use in drug delivery,” he said.

DIFFERENT PROPERTIES

Dr Ramis Castelltort illustrated the point with reference to gold nanoparticles. “Experimenting with the size and shape of these nanoparticles enables us to obtain different properties. For instance, gold nanospheres are very good at penetrating tumorous cells, so that they can be incorporated in the drug delivery coating to improve uptake in the tumorous cells. Gold nanorods have been found to change their shape after excitation with intense pulsed laser irradiation, and nanoshells are particularly useful in imaging applications,” he said.

The problem with conventional drug delivery systems is that ophthalmic formulations do not maintain therapeutic drug concentration in the target tissues for a long duration, due to physiological and anatomical eye barriers, explained Dr Ramis Castelltort. “With nanoparticles, we want to improve the current payload route of administration to the anterior segment and increase drug-corneal residence time. With corneal and stromal barriers, current payloads reach the designated cells only in a very low percentage,” he said.

One possible solution in glaucoma has been to use intraocular implants comprised of a blend of prostaglandin analogues, polylactic acid and/or polylactic-co-glycolic acid (PLGA) for the controlled release of drugs.

Nevertheless, while nanoparticles have the potential to improve ocular tissue exposure from topical administration, they still need to penetrate the ocular mucus layer which serves to protect the eye from allergens, pathogens and foreign bodies, said Dr Ramis Castelltort.

One approach has been to use nanoparticles to develop mucus-penetrating formulations. In preclinical trials of one such drug delivery system, loteprednol etabonate, a corticosteroid specifically designed for ophthalmic inflammatory indications but known to have limited penetration into ocular tissues after topical delivery, was found to have a fourfold increase in rabbit corneas, he said.

Another interesting technique has been to use a nanowafer, a small transparent circular disc that contains arrays of drug-loaded nanoreservoirs, to treat corneal neovascularisation (CNV), said Dr Ramis Castelltort.

In a murine ocular burn model, the slow release of axitinib from the nanowafer increased the drug residence time on the ocular surface and its subsequent absorption into the surrounding ocular tissue. The study concluded that axitinib nanowafer administered once a day was therapeutically twice as effective in the treatment of CNV as axitinib delivered twice a day by topical eye drops.

Many other nanoparticle delivery vehicles are currently being investigated for ocular use, said Dr Ramis Castelltort, including polymeric nanoparticles for ocular delivery of atropine, dendrimer-dexamethasone therapy for the treatment of corneal inflammation, antibiotic delivery through DNA-based nanoparticles, and muco-adhesive nanoparticles to enhance treatment of experimental dry eye.

Marc Ramis Castelltort:
mramis@tbinnovation.com