Development of biodegradable controlled release scleral systems of triamcinolone acetonide.
OBJECTIVE
To develop scleral controlled-release-systems of triamcinolone acetonide (TA) based on biodegradable poly(lactide) (PLA).


METHODS
(1) PLA microspheres containing TA were prepared by a single or double emulsification-solvent evaporation method. Morphology, size, effect of drug input and method of microsphere preparation on drug loading, and in vitro TA release of the microspheres were investigated. (2) Mini-tablets consisting of blank PLA-microspheres and TA (weight ratios of 1:1, 2:1, and 4:1, respectively) were developed and their release profile in vitro was evaluated. (3) The in vitro transscleral diffusion profile was evaluated by placing a PLA-TA (1:1) tablet in a donor chamber and measuring the TA concentration in a receptor chamber. Donor and receptor chambers were separated by rabbit sclera. (4) Two cadaver rabbit eyes received a 1:1 PLA-TA tablet episclerally, which was covered by a scleral patch. TA aqueous humor and vitreous concentrations were measured 5, 10, and 20 days post implantation.


RESULTS
(1) Microsphere average size was 2 μm. The double emulsification method and increasing drug input led to an increase in drug loading and encapsulation. Sustained release of TA over several days from the microspheres in vitro was observed, with the rate of release being affected by their TA content. (2) TA exhibited sustained release profile from the PLA-TA tablets, with the rate of release being affected by the PLA:TA ratio. (3) TA could slowly cross the sclera tissue in vitro, with approximately 21% of the drug loaded in the donor compartment being diffused through the sclera in 45 days. (4) Following scleral administration of the PLA-TA mini-tablets, TA accumulated in the vitreous and aqueous humor of cadaver eyes.


CONCLUSIONS
The PLA-TA microspheres and mini-tablets appear promising for the controlled transscleral delivery of TA and justify further investigation.
Blatsios
G
G
Department of Ophthalmology, Medical School, University of Patras, Rio, Greece.
Tzimas
A S
AS
Mattheolabakis
G
G
Panagi
Z
Z
Avgoustakis
K
K
Gartaganis
S P
SP
D020341:Absorbable Implants; D000818:Animals; D001082:Aqueous Humor / Q000378:metabolism; D003692:Delayed-Action Preparations; D004058:Diffusion; D004655:Emulsions; D005938:Glucocorticoids / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D066298:In Vitro Techniques; D008855:Microscopy, Electron, Scanning; D008863:Microspheres; D011817:Rabbits; D012590:Sclera / Q000378:metabolism* / Q000648:ultrastructure; D013607:Tablets; D014222:Triamcinolone Acetonide / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D014822:Vitreous Body / Q000378:metabolism
D003692:Delayed-Action Preparations; D004655:Emulsions; D005938:Glucocorticoids; D013607:Tablets; D014222:Triamcinolone Acetonide