In vitro and in vivo Release Profile of a Minimally Invasive Triamcinolone Biodegradable Controlled Release Microspheres System for Intravitreous Use

Abstract

Abstract: : Purpose: To study a triamcinolone (TR) biodegradable microspheres system (Micro–Taac) for intraocular use proportionating a prolonged drug release with minimal surgical implantation manipulation. Methods: TR and polylactic–co–glycolic acid (PLGA) were dissolved in acetone to obtain the relationship TR/PLGA 1:1 and 1:2. The TR loading efficiency and quantitative analysis were determined by HPLC. The TR microspheres were characterized by scanning electronic microscopy and by diameter measurements. For in vitro studies amounts of microspheres equivalent to 1mg of TR were incubated in phosphate buffer and the analytical concentrations of TR released were determined against the time. For the in vivo studies amounts of microspheres equivalent to 1mg/0.1mL of TR were injected into the vitreous cavity of sixty albino rabbits utilizing a 27–gauge syringe. The TR concentration was determined in the aqueous and vitreous humors up to 120 days. Results: The Micro–Taac showed uniform particle size (1µm +.0.1) distribution. The encapsulated TR in the microspheres was about 39,53 + 1,80%; 33,01 + 1,80 %; for 1:1 and 1:2 TR/PLGA microspheres, respectively. It was verified that the PLGA amounts in the structural material of microparticle play an important role on the rate of TR release. The time required for release of all free TR was 3 hs while for TR/PLGA 1:1 microspheres was 144 hs and for 1:2 TR/PLGA was 366 hs. The results of the in vivo experiments shown that the free TR not remain above the active for more than 24 days in both, aqueous and vitreous humors. For encapsulated TR/PLGA 1:1, the theoretical therapeutic level of 25µg/ml remained for up to 120 days. Conclusions: Micro–Taac demonstrated a more sustained in vitro and in vivo release profile than its free form. Taken together with its less traumatic implantation requirements, this system may characterize an optimized approach, overcoming most of the implantation barriers faced with the conventional pellet system.

Keywords: pharmacology