Design, optimization, in vitro and in vivo evaluation of triamcinolone acetonide nanocrystals loaded in situ gel for topical ocular delivery

Abstract

Triamcinolone acetonide (TAA), a long-acting synthetic glucocorticoid, is commonly used for the management of posterior uveitis (PU) because of its anti-inflammatory and immunosuppressive characteristics. The commercially available formulation is in the suspension form advised for intravitreal injection, which has a number of serious problems. In the present research work, we prepared TAA nanocrystals (TAA-NCs) using the principles of design of experiments (DoE). The optimized TAA-NCs had a particle size of 243.0 ± 6.5 nm and a yield (%) of 89.4 ± 4.3%. The optimized TAA-NCs were suspended in a dual-responsive in situ gelling system, which has been previously reported by our team. The TAA-NCs loaded in situ gel (TAA-NC-ISG) formulations were evaluated for rheology, stability, in vitro and in vivo characteristics. The ocular pharmacokinetic investigations revealed that TAA-NCs loaded in situ gel achieved higher concentrations (Cmax of TAA-NC-ISG = 854.9 ng/mL) of the drug in vitreous humor and sustained (MRT0–∞ of TAA-NC-ISG = 11.2 h) the drug concentrations for longer duration compared to aqueous suspension of TAA-NCs (TAA-NC-Susp) and aqueous suspension of TAA with 20% hydroxypropyl β-cyclodextrin(TAA-HP-β-CD-Susp) reported in our previous work. This higher exposure of TAA by TAA-NC-ISG is due to the combined effect of the nanometric size of the TAA nanocrystals and the in situ gelling properties of the formulation.