Iurii Belyi_SCIENTIFIC POSTER 2015_3

Sustained delivery of drugs to the posterior segment of the eye has increasingly become a therapeutic option in ophthalmology. Direct delivery of drug to the posterior segment by intravitreal injection or intravitreal implant has demonstrated advantages in treating acute or chronic vitreoretinal diseases. The biodegradable polymeric matrices show benefits compared to non-biodegradable matrices as they are metabolized by the organism and no removal by surgical procedure is necessary. To date, most work has focused on the development and evaluation of implantable devices for creating safe therapeutic concentration of active agent in the posterior segment of the eye.

Purpose:

To develop a new method of intraocular drug delivery to the posterior segment of the eye using a new biodegradable multilayer sustained-release implant.

Material and methods:

We fabricated a multilayer biodegradable intravitreal implant, which has a tube form, 4.0 mm length and 0.3 mm diameter, that is composed of polyvinylpyrrolidone, lactic acid and glycosaminoglycans. The implant consists of 15 layers with the thickness of each layer 10 µm. Layers are connected by transverse septa. The degradation time of the implant depends on transverse septum quantity. According to the construction of implant dexamethasone saturated layers interchange with empty layers. We carried out several in vitro experiments: studying of empty implant resorption; scanning electron microscopy of the implant; in vitro dexamethasone release profiles. An intravitreal empty implant was placed in 5 ml of 0.9% NaCl solution in a closed vial at 37° C. Measurements of the implant time resorption was carried out from the beginning of the experiment to the full visual disappearance of the implant in the test- tube. The morphology of the implant was analyzed by scanning electron microscopy (JEOL JSM-6610). Prior to microscopy analysis samples were gold-coated, than directly observed at an accelerating voltage of 15 kV. We estimated drug release function of the implant comprising dexamethasone in dosage 300 µg. The intravitreal dexamethasone implant was placed in 5 ml of 0.9% NaCl solution in a closed test-tubes. Those tubes were placed inside a horizontal incubation shaker at 37° C. At predetermined intervals, the entire volume was sampled, and 3 mL fresh 0,9% NaCl solution was added to the sample vial to approximate a perfect sinking condition during 32 days. The amount of active agent in solution was measured by UV-spectrophotometer at the wavelength of 242 nm for dexamethasone with calibration curve.

Results:

Full resorption time of the empty implant was 31 days. The presence of water leads to hydrolysis of the implant polymer matrix. In the first step water wets the surface and diffuses into the polymer. As the degradation proceeds, polymer chain segments start to dissolve and polymer erosion takes place. At the end of the process the polymer is completely absorbed and disappeared due to high water solubility of monomers. Scanning electron microscopy has shown the laminated structure of the implant, presence of the transverse septa between each layer. In-vitro release of dexamethasone from the implant is described by exponential curve with dexamethasone concentration increasing from 1 to 3 day and decreasing on the 4 day. Decreasing of the concentration is respond to solution of empty layer. We determined 8 similar cycles of dexamethasone release during the whole period of the implant degradation. There was a residual dexamethasone concentration on 32th day.

Conclusion:

The new fabricated biodegradable multilayer intravitreal implant provides periodical release of active agent without it therapeutic concentration overdose.

Contact Details:

Email: nauka@mntk.kaluga.ru
Cell Phone: /+74842505795