Triamcinolone Acetonide–loaded Pellets Obtained From PLGA Microparticles for Intravitreous Controlled Drug Release

Abstract

Abstract: : Purpose: To study the in vitro and in vivo release profile of a new poly lactic–co–glycolic acid (PLGA)–based triamcinolone–load pellets Methods: Drug–free and triamcinolone–loaded microparticles were prepared using extrusion method, and the pellets prepared by compression using a matrix with 1 mm of diameter. The theoretical drug loaded in microspheres was 0.85mg. The systems were characterized using optical and electronic microscopy. The determination of the drug loading was carried out by PHLC. The in vitro release kinetics was carried out by incubation of the pellets in phosphate buffer pH 7.4 and measuring the dissolved TR by HPLC. For in vivo experiments the pellets were implanted in the scleral region of the rabbit’s right eye. At the appropriated time the animals were sacrificed and both aqueous and vitreous humors were collected and freeze for posterior analysis. The concentrations of the released TR were determined by HPLC. Results: The encapsulation efficiency of triancinolone was about 92% in relation of the theoretical loading of 0.85mg. The analytical TR concentration was determined as 0.8mg per pellet. The final dimensions of the obtained pellets were 1mm diameter and 1.8mm length and 1.6mg + 0.136 mg of total weight. The in vitro TR release was followed for the least 8 weeks and the results showed a sigmoidal profile with slow release in the initial first week increasing significantly in above times. For the in vivo release the concentration of TR dissolved in the humor vitreous increased reaching a maximum in the first week following by a slowly decrease at least 8 weeks. The decrease of TR concentration above the first week varied linearly with the time revealing well controlled within the 8 experimental weeks. Interestingly, the accumulative TR released in the in vitro experiment in the first week is in agreement with in vivo assay but above this time the release rate was lesser than that elimination rate making with that TR concentration diminishes slowly. Conclusions: These results suggest that the intravitreal implant would be a promising system for controlled and sustained delivery of triamcinolone acetonide to the posterior segment of the eye

Keywords: corticosteroids