Using ultrasound and photoacoustics to monitor in situ forming implant structure and drug release

Abstract

Most chemotherapeutics (CTs) are delivered systemically, causing nausea, hair loss, fatigue and a compromised immune system. Biocompatible in situ forming implants (ISFIs) are drug delivery vehicles which are injected as a liquid before solidifying in tissues and ultimately breaking down. By dissolving CTs in an ISFI solution, they can be injected directly to the tumour site and released in a controllable manner. ISFIs can provide localized, continuous release of CT, reducing side effects. The complex phase change of ISFIs causes a variable release rate of CT. In this work, photoacoustic (PA) imaging was used for the first time to monitor a dye (mimicking CT) diffusing into a tissue mimicking phantom while quantitative ultrasound (QUS) was used to monitor the changes in the ISFI structure. ISFIs made of poly(lactic-co-glycolic acid) and Janus Green B dye dissolved in N-methyl-2-pyrrolidone in a 39:1:60 ratio were injected in tissue mimicking polyacrylamide phantoms containing titanium oxide. ISFI structure and drug release was monitored over 72 hours. At each time point, 47 planes of the phantoms were imaged using both PA (700nm) and US using the VevoLAZR system. Regions of interest within and proximal to the ISFI were selected, and average PA and QUS parameters were determined for each plane as a function of time postimplantation. This work shows the potential of PA and QUS for monitoring kinetic drug release.