Pharmacokinetic Analysis of a Novel 3D-Printed Thermoplastic Polyurethane Continuous Sub-Tenon Drug Delivery Device in Rabbit Eyes

Objective To evaluate the pharmacokinetic characteristics of a novel 3D-printed thermoplastic polyurethane continuous drug delivery device in rabbit eyes' aqueous humor and vitreous humor. Methods A continuous sub-tenon drug delivery device (CSDDD) was designed using computer-aided design and fabricated via stereolithography 3D printing. The device was implanted sub-tenon in the temporal side of the right eye in rabbits. 1 mL of triamcinolone acetonide (TA) carbomer gel (40 mg/mL) was injected into the drug reservoir for sustained release in CSDDD group. The control group was administered a single subconjunctival (SC) injection of TA at the same dose and concentration. The experimental rabbits were randomly allocated into two groups, each comprising eight temporal subgroups corresponding to 0.5 hr, 1 hr, 3 hr, 6 hr, 24 hr, 48 hr, 7 days, and 14 days post-intervention. To ensure data reliability, five biological replicates were maintained at each time point across all subgroups. Aqueous humor and vitreous humor samples were collected and High-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) was employed to determine TA concentration. Following the exclusion of outliers (maximum and minimum values), triplicate samples from each time point in each group were retained for subsequent statistical analysis. Descriptive statistical analysis was performed using SPSS 20.0, while pharmacokinetic parameters were calculated with DAS 2.0 software. Results In the aqueous humor, the TA concentration in the CSDDD group remained stable at approximately 0.5 ~ 0.6 μg/mL from 0.5 to 6 hr, peaked at 0.763 ± 0.275 μg/mL by 24 hr, and persisted at 0.641 ± 0.113 μg/mL at 48 hr, followed by a gradual decline thereafter. While in the SC group, the peak concentration was (1.930±0.190 μg/mL) at 1 hr, followed by a rapid decrease. In the vitreous humor, the peak TA concentration in the CSDDD group was (1.627±0.674 μg/mL) at 6 hr, with a sustained release over 14 days. In contrast, the SC group exhibited a peak concentration of (0.496±0.417 μg/mL) at 0.5 hr, remaining at low levels throughout. The CSDDD group showed significantly higher concentration and AUC0-14d in both the vitreous and the aqueous humour relative to the SC group. Conclusion The 3D-printed CSDDD demonstrated effective sustained drug release, achieving prolonged therapeutic concentrations of TA in both the aqueous and vitreous, surpassing the SC group. This device presents a promising alternative for sustained ocular drug delivery.