Pharmaceutical research · 2026
Injectable in-situ Forming Lipid Liquid Crystal for Long-acting Fluocinolone Release in Posterior Ocular Therapy: In-vitro and In-vivo Evaluations.
СтатьяНазвание и аннотация: Перевод в очереди
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Karimi Malihe, Abrishami Mojtaba, Farzadnia Mehdi, Kamali Hossein, Malaekeh-Nikouei Bizhan
Аннотация
OBJECTIVE: Intravitreal injection is a preferred route for targeted drug delivery to the posterior eye. However, commercial non-biodegradable polymeric implants for fluocinolone acetonide (FA) often necessitate surgical removal after long-term release, reducing patient compliance and increase surgical risks. Biodegradable polymeric implants also typically exhibit an initial burst release. This study explores the development of an innovative biodegradable in-situ forming lipid liquid crystal (ISF-LLC) formulation for sustained FA delivery over two months via a single intravitreal injection without burst release.
METHODS: The optimized formulation, developed using Design of Experiment software, comprised phosphatidylcholine and sorbitan monooleate (PC: SMO 30/70 w/w%) with N-methyl-2-pyrrolidone (NMP 30w/w%).
RESULTS: The ISF-LLC formulation exhibited pseudoplastic behavior, excellent syringeability, stability, and a hexagonal crystalline structure. In-vivo pharmacokinetic analysis in rabbit vitreous humor revealed a slow, controlled release rate of 0.49 ± 0.01 μg/day over 60 days (within the clinical range 0.2-0.6 μg/day), with no burst release during the first 7 days (0.22 ± 0.01 μg/day). The vitreal half-life was 22.80 ± 0.51 days, and FA was undetectable systemically. Quantitative histopathology showed no significant differences in retinal thickness (203-209 μm vs. 203 ± 2 μm, p > 0.05) or inflammatory cell count (1-3 vs. 1.3 ± 0.6 cells/field, p > 0.05) between treated and control groups. No retinal damage or systemic toxicity was observed.
CONCLUSIONS: The injectable biodegradable ISF-LLC formulation is a promising controlled-release, long-acting platform for intravitreal drug delivery, eliminating initial burst release and need for surgical removal, thereby improving patient outcomes in ocular therapy.
METHODS: The optimized formulation, developed using Design of Experiment software, comprised phosphatidylcholine and sorbitan monooleate (PC: SMO 30/70 w/w%) with N-methyl-2-pyrrolidone (NMP 30w/w%).
RESULTS: The ISF-LLC formulation exhibited pseudoplastic behavior, excellent syringeability, stability, and a hexagonal crystalline structure. In-vivo pharmacokinetic analysis in rabbit vitreous humor revealed a slow, controlled release rate of 0.49 ± 0.01 μg/day over 60 days (within the clinical range 0.2-0.6 μg/day), with no burst release during the first 7 days (0.22 ± 0.01 μg/day). The vitreal half-life was 22.80 ± 0.51 days, and FA was undetectable systemically. Quantitative histopathology showed no significant differences in retinal thickness (203-209 μm vs. 203 ± 2 μm, p > 0.05) or inflammatory cell count (1-3 vs. 1.3 ± 0.6 cells/field, p > 0.05) between treated and control groups. No retinal damage or systemic toxicity was observed.
CONCLUSIONS: The injectable biodegradable ISF-LLC formulation is a promising controlled-release, long-acting platform for intravitreal drug delivery, eliminating initial burst release and need for surgical removal, thereby improving patient outcomes in ocular therapy.