Weldon School of Biomedical Engineering, Purdue University, 206 S. Martin Jischke Dr., West Lafayette, IN 47907, USA.
Basic Medical Sciences, College of Veterinary Medicine, Purdue University, 625 Harrison St., West Lafayette, IN 47907, USA.
J Control Release. 2019 Sep 10;309:289-301. doi: 10.1016/j.jconrel.2019.07.019. Epub 2019 Jul 16.
In situ forming implants (ISFIs) form a solid drug-eluting depot, releasing drug for an extended period of time after a minimally-invasive injection. Clinical use of ISFIs has been limited because many factors affect drug release kinetics. The aim of this study was to use diffusion-weighted MRI (DWI) to noninvasively quantify spatial-temporal changes in implant diffusivity in situ. ISFIs were formed using poly(lactic-co-glycolic) acid, with a molecular weight of either 15 kDa or 52 kDa, and fluorescein as the mock drug. Drug release, polymer erosion, polymer degradation, and implant diffusivity were analyzed in vitro over 21 days. DWI was also performed in vivo over 5 days. Spatial diffusivity maps of the implant were generated using DWI data. Results showed constant diffusivity at the implant shell ((1.17 ± 0.13) × 10 mm/s) and increasing diffusivity within the interior over time (from (0.268 ± 0.081) × 10 mm/s during day 1 to (1.88 ± 0.04) × 10 mm/s at 14 d), which correlated with increasing porosity of the implant microstructure. Implants formed in vivo followed the same diffusivity trend as those in vitro. This study validates the use of DWI to provide novel functional information about implant behavior through its ability to noninvasively characterize transport properties within the implant both in vitro and in vivo.
原位形成植入物（ISFI）形成固体药物洗脱库，在微创注射后可延长药物释放时间。由于许多因素会影响药物释放动力学，因此 ISFI 的临床应用受到限制。本研究旨在使用扩散加权 MRI（DWI）非侵入性地定量原位植入物扩散率的时空变化。ISFI 由分子量分别为 15 kDa 和 52 kDa 的聚（乳酸-共-乙醇酸）和荧光素作为模拟药物形成。在 21 天内进行体外药物释放、聚合物侵蚀、聚合物降解和植入物扩散率分析。还在 5 天内进行了体内 DWI。使用 DWI 数据生成植入物的空间扩散率图。结果显示，植入物壳的扩散率保持不变（（1.17±0.13）×10mm/s），而内部的扩散率随时间增加（从第 1 天的（0.268±0.081）×10mm/s 增加到第 14 天的（1.88±0.04）×10mm/s），这与植入物微观结构的孔隙率增加有关。体内形成的植入物与体外植入物具有相同的扩散趋势。这项研究验证了 DWI 的使用，通过其在体外和体内非侵入性地表征植入物内的传输特性的能力，为提供关于植入物行为的新功能信息提供了可能性。
