Noninvasive characterization of in situ forming implant diffusivity using diffusion-weighted MRI

JOURNAL OF CONTROLLED RELEASE

卷:309

Article

Hopkins, Kelsey A.¹  Vike, Nicole²  Li, Xin¹  Kennedy, Jacqueline¹  Simmons, Emma¹  Rispoli, Joseph^1,3,4  Solorio, Luis^1,4 

[1] Purdue Univ, Weldon Sch Biomed Engn, 206 S Martin Jischke Dr, W Lafayette, IN 47907 USA

[2] Purdue Univ, Coll Vet Med, Basic Med Sci, 625 Harrison St, W Lafayette, IN 47907 USA

[3] Purdue Univ, Elect & Comp Engn, 465 Northwestern Ave, W Lafayette, IN 47907 USA

[4] Purdue Univ, Ctr Canc Res, 201 S Univ St, W Lafayette, IN 47907 USA

关键词: in situ forming implants;    Controlled release;    Drug delivery;    MRI;    Diffusion-weighted imaging;    Diffusivity;   

DOI  :  10.1016/j.jconrel.2019.07.019

来源: Elsevier

【 摘 要 】

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) x 10(-3) mm(2)/s) and increasing diffusivity within the interior over time (from (0.268 +/- 0.081) x 10(-3) mm(2)/s during day 1 to (1.88 +/- 0.04) x 10(-3) mm(2)/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.

【 授权许可】

Free