Sustained intravitreal delivery of triamcinolone acetonide via in situ forming lipid liquid crystals: in-vitro and in-vivo evaluations.

Posterior segment disorders remain challenging to manage due to limitations in ocular drug delivery. Although intravitreal triamcinolone acetonide (TA) is effective, it requires repeated administration, highlighting the need for sustained-release systems. This study aimed to develop in situ sustained-release formulations of TA using lipid liquid crystals (LLCs). Formulations were prepared with glyceryldioleate (GDO), phosphatidylcholine (PC), and N-methyl pyrrolidone (NMP) at PC:GDO ratios of 50:50, 40:60, and 60:40. A TA-hydroxypropyl-β-cyclodextrin (HPβCD) complex was also prepared. The formulations were characterized for rheological properties, morphology, degradation, and water uptake. In-vitro release was assessed in phosphate-buffered saline (pH 7.4), while in-vivo pharmacokinetics were evaluated in rabbits, comparing a selected LLC formulation with a TA suspension. The F5 formulation (40:60 PC: GDO) achieved sustained release of 35.4% over one month and exhibited superior stability, with 24.9% less degradation compared to F6, which showed undesirable drug crystallization. The TA-HPβCD complex demonstrated an even slower release (28%). F4 (50:50 PC: GDO) was selected as the optimized formulation, demonstrating the lowest water absorption and degradation with a consistent release profile. In-vivo studies confirmed that LLCs provided more controlled and prolonged release compared with conventional TA suspension. In conclusion, LLC-based TA formulations offer a promising strategy for sustained intravitreal drug delivery, with biodegradability, ease of preparation, and prolonged therapeutic levels.