An eye for drug delivery
A drug-eluting contact lens that dispenses a constant amount of medication for over 30 days may provide an alternative to eye drops for treating conditions such as glaucoma.
The team behind the development in the USA says the two-layer structure – an inner drug-bearing, biodegradable, biocompatible, PLGA film coated with hydrogel pHEMA – achieves zero-order kinetics (a constant amount of release per day). It dispenses 134µg of ciprofloxacin or fluorescin antibiotic each day for 30 days – the longest duration for which contact lenses are approved for continuous wear by the USA’s Food and Drug Administration (FDA).
In comparison, the researchers say drug-dispensing lenses developed by other groups have displayed non-linear kinetics, where a burst of medication is delivered in the first few hours, followed by dwindling amounts that are too low to be therapeutic.
Dr Daniel Kohane, Director of the Laboratory for Biomaterials and Drug Delivery at Children’s Hospital Boston, explains, ‘A big part of it is that we rely on a hydrophobic polymeric core. Other people have, by and large, taken the hydrogel and soaked it with drugs, or modified it so that the drugs are entrapped within it, or put micelles and liposomes on the surface. The amount [of medication] you can put in [our] film dwarfs what you can dissolve throughout the matrix’.
He adds, ‘There is a whole science behind why macroscopic objects release slowly – the surface area-to-volume ratio becomes smaller. Also, hydrophobic systems are generally better at controlling drug release than hydrophilic hydrogels, [which] release more rapidly’.
The new lens overcomes the need for taking eye drops several times a day. Due to blinking and tearing, only up to seven per cent of the dosage is absorbed by the eye, says Kohane.
Both PLGA and pHEMA were chosen as they are well studied materials, approved by the FDA for ocular use. Solvent casting of the PLGA film, which has a five-millimetre clear optical aperture, ensures uniformity of the medication in the material. The film is then coated on all sides with two layers of pHEMA using UV polymerisation. The resulting prototype is about 450µm thick with an outside diameter of 16mm.
In vitro trials in 15ml phosphate-buffered saline at pH7.4 and 37ºC replicated the human tear film conditions.
According to the results, lens manufacture and the drug delivery process do not affect the antibiotics’ effectiveness. Meanwhile, increasing the proportion of PLGA to medication, or its molecular mass, slows down release while maintaining zero-order kinetics. This could enable the rates of drug elution to be adjusted. ‘There are similar considerations for the hydrogel – the density, thickness, etc,’ says Kohane.
Professor Pankaj Vadgama, Director of the Interdisciplinary Research Centre in Biomedical Materials at Queen Mary University of London, UK, comments, ‘Drug delivery control by biomaterials is a major challenge because of the lack of control over the dynamics. This [research] goes a long way to provide the predictability and constancy of release’.
He adds, ‘However, there is a need for more physiological evaluation, given that the eye presents a rapidly drying tear interface that is different from the standard solution used for the study. Moreover, the presence of a drug in a lens shows up as a distinct opaque phase, which has cosmetic implications and may not be well tolerated by the patient’.
The research in Boston, collaborated on by scientists at the Massachusetts Eye and Ear Infirmary and MIT, is still in its early phase with in vivo trials just beginning. Plans are afoot to develop similar prototypes using different hydrogels, film materials and antibiotics.
The ability to store the lenses at room temperature is another area to explore, as the PLGA component degrades over time.Materials World Magazine, 01 Sep 2009
The team behind the development in the USA says the two-layer structure – an inner drug-bearing, biodegradable, biocompatible, PLGA film coated with hydrogel pHEMA – achieves zero-order kinetics (a constant amount of release per day). It dispenses 134µg of ciprofloxacin or fluorescin antibiotic each day for 30 days – the longest duration for which contact lenses are approved for continuous wear by the USA’s Food and Drug Administration (FDA).
In comparison, the researchers say drug-dispensing lenses developed by other groups have displayed non-linear kinetics, where a burst of medication is delivered in the first few hours, followed by dwindling amounts that are too low to be therapeutic.
Dr Daniel Kohane, Director of the Laboratory for Biomaterials and Drug Delivery at Children’s Hospital Boston, explains, ‘A big part of it is that we rely on a hydrophobic polymeric core. Other people have, by and large, taken the hydrogel and soaked it with drugs, or modified it so that the drugs are entrapped within it, or put micelles and liposomes on the surface. The amount [of medication] you can put in [our] film dwarfs what you can dissolve throughout the matrix’.
He adds, ‘There is a whole science behind why macroscopic objects release slowly – the surface area-to-volume ratio becomes smaller. Also, hydrophobic systems are generally better at controlling drug release than hydrophilic hydrogels, [which] release more rapidly’.
The new lens overcomes the need for taking eye drops several times a day. Due to blinking and tearing, only up to seven per cent of the dosage is absorbed by the eye, says Kohane.
Both PLGA and pHEMA were chosen as they are well studied materials, approved by the FDA for ocular use. Solvent casting of the PLGA film, which has a five-millimetre clear optical aperture, ensures uniformity of the medication in the material. The film is then coated on all sides with two layers of pHEMA using UV polymerisation. The resulting prototype is about 450µm thick with an outside diameter of 16mm.
In vitro trials in 15ml phosphate-buffered saline at pH7.4 and 37ºC replicated the human tear film conditions.
According to the results, lens manufacture and the drug delivery process do not affect the antibiotics’ effectiveness. Meanwhile, increasing the proportion of PLGA to medication, or its molecular mass, slows down release while maintaining zero-order kinetics. This could enable the rates of drug elution to be adjusted. ‘There are similar considerations for the hydrogel – the density, thickness, etc,’ says Kohane.
Professor Pankaj Vadgama, Director of the Interdisciplinary Research Centre in Biomedical Materials at Queen Mary University of London, UK, comments, ‘Drug delivery control by biomaterials is a major challenge because of the lack of control over the dynamics. This [research] goes a long way to provide the predictability and constancy of release’.
He adds, ‘However, there is a need for more physiological evaluation, given that the eye presents a rapidly drying tear interface that is different from the standard solution used for the study. Moreover, the presence of a drug in a lens shows up as a distinct opaque phase, which has cosmetic implications and may not be well tolerated by the patient’.
The research in Boston, collaborated on by scientists at the Massachusetts Eye and Ear Infirmary and MIT, is still in its early phase with in vivo trials just beginning. Plans are afoot to develop similar prototypes using different hydrogels, film materials and antibiotics.
The ability to store the lenses at room temperature is another area to explore, as the PLGA component degrades over time.Materials World Magazine, 01 Sep 2009
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