טכניון מכון טכנולוגי לישראל
הטכניון מכון טכנולוגי לישראל - בית הספר ללימודי מוסמכים  
M.Sc Thesis
M.Sc StudentSheskin Tali
SubjectPolymeric Systems for Ocular Drug Delivery
DepartmentDepartment of Biomedical Engineering
Supervisors Professor Emeritus Noah Lotan
Professor Orna Geyer
Ms. Sarit Sivan


Abstract

Ocular drugs are commonly applied for a localized action on the surface or in the interior of the eye. A major problem in ocular therapeutics is the attainment of an optimal drug concentration at the site of action. Nowadays, there is a significant effort in developing drug delivery systems for ophthalmic administration which can provide controlled and continuous drug delivery.

In this research, modalities for the controlled release of local anaesthetics to the eye(s) during 48 hours comprising injectable and biodegradable nanospheres, which contain local anesthetic drugs, Lidocaine or Tetracaine, and poly(anhydrides) as the polymeric carrier were studied. These modalities may level out pain in cases of cornea injuries and following photorefractive-keratectomy.

Three polymeric carriers, namely poly(sebacic-acid), poly(sebacic acid-co-ricinoleic acid) and poly(fumaric acid-co-sebacic acid) were used. The resulting nanospheres (average diameter of 100nm to 700nm), release in-vitro their drug contents within 24 to 80 hours depending on the poly(anhydride) carrier type, where only the poly(sebacic-acid) nanospheres release their content within two days.

Theoretical analyses of the drug release kinetics from biodegradable nanospheres were performed. The dependence of the drug released amount on diffusion, surface/bulk-erosion and drug dissolution mechanisms as well as the role played by the spheres size-inhomogeneity are explored. The calculations show a good fit of the diffusion, drug dissolution and bulk-erosion model to the experimental data, in agreement with previously reported results.

Finally, preliminary in-vivo experiments using sterilized Tetracaine-loaded poly(sebacic-acid) nanospheres show a partial anesthetic effect of 6-8 hours, suggesting a rapid clearance of the drug.