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J Ocul Pharmacol Ther ; 34(5): 416-425, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29584529

RESUMO

PURPOSE: To achieve a safer alternative to intravitreal injection of corticosteroids, we developed and characterized triamcinolone acetonide-loaded liposomes formulations (TA-LFs) to be used topically for vitreoretinal drug delivery. METHODS: Four different 0.2% TA-LFs (TA-LF1 to TA-LF4) were generated and submitted to physicochemical characterization. Posteriorly, an ex vivo diffusion assay was performed using rabbit corneas as membranes. Finally, concentrations of triamcinolone acetonide (TA) were determined by high-performance liquid chromatography in ocular tissues from New Zealand white rabbits after multiple topical doses of TA-LF2 (6 times per day, 14 days). In addition, toxicity and tolerability of TA-LF2 was evaluated by cell viability assay and eye examination of study animals, respectively. RESULTS: TA-LF2 was the most stable formulation maintaining a stable hidrogenion potential (pH) at 30 and 40°C and even improving encapsulation with higher temperature. TA-LF2 and TA-LF3 presented the best diffusion performance in vitro reaching the highest TA concentrations after 8 h of follow-up. In vivo diffusion and pharmacokinetics analysis showed that concentrations of TA in retina and vitreous reached the highest peak at 12 h after topical administration of TA-LF2 (252.10 ± 90.00 ng/g and 32.6 ± 10.27 ng/g, respectively) and subsequently decline to 24.0 ± 11.72 ng/g and 19.5 ± 13.14 ng/g, respectively, at 14 days of follow-up. Finally, cell viability was unaffected by TA-LF2, and no increase in intraocular pressure nor ocular alterations were observed after topical administration of this formulation in rabbits. CONCLUSION: TA-loaded liposomes, administered topically, can deliver TA in the vitreous cavity and reach the retina efficiently.


Assuntos
Sistemas de Liberação de Medicamentos , Triancinolona Acetonida/farmacocinética , Administração Tópica , Animais , Sobrevivência Celular , Composição de Medicamentos , Humanos , Lipossomos/administração & dosagem , Lipossomos/farmacocinética , Coelhos , Triancinolona Acetonida/administração & dosagem
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