Sustained Intravitreal Delivery of Triamcinolone Acetonide via In Situ Forming Lipid Liquid Crystals: In-vitro and In-vivo evaluations.

Posterior segment disorders represent a leading cause of vision impairment worldwide and remain challenging to manage due to limitations in ocular drug delivery. Although intravitreal injections of triamcinolone acetonide (TA) are effective, they are invasive and require 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 28% w/w N-methyl pyrrolidone (NMP) at PC:GDO ratios of 50:50, 40:60, and 60:40. Additionally, a TA-hydroxypropyl-β-cyclodextrin (HPβCD) complex was prepared. The formulations were characterized for rheological properties, morphology, degradation behavior, 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 (right eye) with a TA suspension (left eye). 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 (60:40 PC: GDO), which showed undesirable drug crystallization. The TA-HPβCD complex demonstrated an even slower release (28%). F4 (50:50 PC: GDO) was selected as optimized formulation, demonstrated the lowest water absorption and degradation with consistent release profile. In-vivo studies further confirmed that LLCs provided a more controlled and prolonged release compared with conventional TA suspension. In conclusion, LLC-based formulations of TA offer a promising strategy for sustained intravitreal drug delivery. Their biodegradability, ease of preparation, and ability to provide prolonged therapeutic levels highlight their potential for improving the management of posterior ocular diseases.