Pharmacokinetic and toxicity investigations of a new intraocular lens with a dexamethasone drug delivery system: a pilot study.
OBJECTIVE
To investigate the short-term safety and pharmacokinetic behavior of a new intraocular lens containing a dexamethasone drug delivery system (IOL-DDS) in rabbit eyes.


METHODS
A modified polymethylmethacrylate IOL containing a biodegradable dexamethasone DDS was implanted into the posterior chamber of the right eyes of 9 New Zealand white rabbits. Serial slitlamp and indirect ophthalmoscopic examinations (including grading of intraocular inflammation) were performed. After 3, 6 and 9 days, the rabbits were euthanized and the globes were removed for histological examination and for determination of dexamethasone levels in the aqueous humor and in the vitreous. Analysis of dexamethasone concentrations was performed by ELISA.


RESULTS
Therapeutic concentrations of dexamethasone were detectable in the aqueous and vitreous of the study eyes throughout the 9-day period in all tested animals. The mean aqueous dexamethasone concentration (ng/ml, +/- SD) was 1,015.42 (+/- 43.05), 970.11 (+/- 32.47) and 757.58 (+/- 30.19) and the mean vitreous concentration (ng/ml, +/- SD) was 399.82 (+/- 38.05), 287.38 (+/-34.47) and 268.15 (+/- 32.00) at 3, 6 and 9 days after the surgical procedure, respectively. No corneal or retinal histological changes were observed during the study period.


CONCLUSIONS
The IOL-DDS is effective in delivering therapeutic concentrations of dexamethasone to the aqueous and vitreous, without acute damage to the cornea and retina. Further controlled studies in the same animal model are under way to determine the potential value of this lens in the prevention and treatment of inflammation following cataract surgery.
Siqueira
Rubens C
RC
Retinal and Vitreous Specialized Center of the Eye Hospital of Rio Preto, Rio Preto, Brazil. rubenssiqueira@terra.com.br
Filho
Elias Ribeiro
ER
Fialho
Sílvia L
SL
Lucena
Levy R
LR
Filho
Alfredo Maia
AM
Haddad
Antônio
A
Jorge
Rodrigo
R
Scott
Ingrid U
IU
Cunha
Armando da Silva
Ada S
D000818:Animals; D001082:Aqueous Humor / Q000378:metabolism*; D001682:Biological Availability; D002387:Cataract Extraction; D003907:Dexamethasone / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000633:toxicity; D016503:Drug Delivery Systems; D004797:Enzyme-Linked Immunosorbent Assay; D005938:Glucocorticoids / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000633:toxicity; D019344:Lactic Acid; D019654:Lens Implantation, Intraocular; D007910:Lenses, Intraocular; D008297:Male; D010865:Pilot Projects; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers; D019904:Polymethyl Methacrylate; D011817:Rabbits; D014822:Vitreous Body / Q000378:metabolism*
D005938:Glucocorticoids; D011108:Polymers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D003907:Dexamethasone; D019904:Polymethyl Methacrylate