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

Area of Science:

• Biomaterials Science
• Medical Imaging
• Drug Delivery Systems

Background:

• In situ forming implants (ISFIs) offer extended drug release via minimally-invasive injection.
• Clinical application of ISFIs is hindered by complex drug release kinetics.
• Noninvasive methods are needed to understand ISFI behavior in situ.

Purpose of the Study:

• To utilize diffusion-weighted MRI (DWI) for noninvasive quantification of spatial-temporal changes in ISFI diffusivity.
• To correlate DWI-derived diffusivity with polymer erosion and degradation.
• To validate DWI's utility for characterizing ISFI transport properties in vitro and in vivo.

Main Methods:

• ISFIs were fabricated using poly(lactic-co-glycolic) acid (PLGA) of two molecular weights.
• Fluorescein was used as a model drug to assess release kinetics.
• In vitro and in vivo studies analyzed drug release, polymer erosion, degradation, and implant diffusivity using DWI over 21 and 5 days, respectively.

Main Results:

• DWI revealed constant diffusivity at the implant shell and increasing diffusivity in the interior over time.
• Increased interior diffusivity correlated with enhanced porosity in the implant microstructure.
• In vivo ISFI diffusivity trends mirrored in vitro observations.

Conclusions:

• DWI successfully provides noninvasive, functional information on ISFI behavior.
• The study validates DWI as a tool to characterize transport properties within ISFIs.
• This technique can advance the understanding and clinical use of ISFIs.