3D打印Tenon囊下曲安奈德持续给药装置在兔眼房水中的药物代谢动力学研究
Pharmacokinetic study of triamcinolone acetonide based on the 3D printed ocular sustained delivery device in aqueous humor of rabbit eyes
叶丽妍 1梁露允 1刘晓岚 1段毅琴2
作者信息
- 1. 暨南大学附属爱尔眼科医院 广州爱尔眼科医院,广州 510071;暨南大学附属第一医院,广州 510632
- 2. 暨南大学附属爱尔眼科医院 广州爱尔眼科医院,广州 510071;长沙爱尔眼科医院,长沙 410007
- 折叠
摘要
目的 评价应用 3D 打印的Tenon囊下曲安奈德持续给药装置在兔眼房水中的药物代谢动力学特征.方法 实验研究.24 只成年新西兰兔为实验动物,将应用 3D药物打印技术制备的给药装置植入于右眼颞侧Tenon囊下,通过装置注射曲安奈德凝胶(40 mg),在注药后0.5 h、1 h、3 h、6 h、24 h、48 h、7 d、14 d分别随机处死3 只家兔取房水样本.采用高效液相色谱串联质谱法测曲安奈德浓度,以SPSS 20.0 进行统计学分析,以药理学计算软件DAS 2.0 单房室模型拟合计算药代动力学参数.结果 利用 3D 打印技术制作的Tenon囊下持续给药装置搭载曲安奈德凝胶给药后,曲安奈德在眼局部达到有效治疗浓度(0.01 μg/mL),并维持一定的作用时间,注药后 0.5 h浓度为(0.548±0.346)μg/mL,约为有效治疗浓度的 50 倍;随后浓度缓慢增加,注药后 24 h 达到峰浓度(0.763±0.337)μg/mL,约为有效治疗浓度的 70 倍;随后浓度下降,注药后14 d浓度为(0.023±0.017)μg/mL,约为有效治疗浓度的 2 倍.房水中药代动力学参数:药物半衰期=33.564 h、药物浓度-时间累积曲线下面积=87.713 μg/mL×h、峰浓度=1.020 μg/mL、达峰时间=24 h.结论 3D打印兔眼Tenon囊下曲安奈德持续可控给药装置制作程序可行,经该装置曲安奈德在兔眼房水中持续达到有效治疗浓度,给药装置安全有效.
Abstract
Objective To evaluate the pharmacokinetics of a 3D-printed triamcinolone acetonide sustained drug delivery device in the aqueous humor of rabbit eyes.Methods This was an experimental study.The experiment included twenty-four adult New Zealand rabbits.The drug delivery device using 3D bioprinting was placed under Tenon's capsule on the temporal side of the right eye,and triamcinolone acetonide gel(40 mg)was delivered through it.At each time point,three rabbits were slaughtered at random to collect aqueous humor samples at 0.5 h,1 h,3 h,6 h,24 h,48 h,7 d,and 14 d following injection.High-performance liquid chromatography-tandem mass spectrometry was employed to determine the concentration of triamcinolone acetonide.SPSS 20.0 was employed to conduct descriptive statistical analysis,and the DAS 2.0 pharmacokinetic software was employed to calculate pharmacokinetic parameters using a one-compartment model.Results The 3D-printed new ocular medication delivery device exhibited foldability,extensibility,and good drug permeability,which could be used to implant subtenons in rabbit eyes.Triamcinolone acetonide achieved an effective therapeutic concentration in the eye and maintained its impact for a period of time.At 0.5 h post-injection,the concentration was(0.548±0.346)μg/mL.It steadily increased,peaking at(0.763±0.337)μg/mL at 24 h and kept decreasing to(0.023±0.017)μg/mL until 14 d.Pharmacokinetic parameters for the aqueous humor were:half time=33.564 h,area under the concentration-time curve=87.713 μg/mL×h,maximum concentration=1.020 μg/mL,time to maximum concentration=24 h.Conclusion The 3D-printed triamcinolone acetonide sustained and controlled drug delivery device for implantation under the Tenon's capsule in rabbit eyes is feasible due to its fabrication process.The device is found to be both safe and effective,and it consistently obtains effective therapeutic concentrations in the aqueous humor of rabbit eyes when triamcinolone acetonide is administered through it.
关键词
打印,3D/装置,眼部/囊,Tenon/曲安奈德/高效液相色谱串联质谱法/药代动力学Key words
3D printing/Ocular device/Tenon capsule/Triamcinolone acetonide/High-performance liquid chromatography-tandem mass spectrometry/Pharmacokinetics引用本文复制引用
基金项目
湖南省自然科学基金课题(2020JJ4001)
湖南省科技创新计划项目(2018SK50103)
出版年
2024
NETL
NSTL
万方数据