Computed tomography of Lipiodol‐loaded biodegradable pasty polymer for implant visualization

Abstract

Targeted delivery of drug-loaded implants for regional drug therapy has become an important approach to therapy. Simple and reproducible imaging methodologies to evaluate the implant noninvasively are needed. The goal of this work was to noninvasively evaluate the visibility, shape and degradation of a biodegradable implant containing Lipiodol (an X-ray contrast medium) by computed tomography (CT). For in vitro evaluation, Lipiodol was incorporated in poly(sebacic-co-ricinoleic acid) [P(SA:RA)], a biodegradable injectable pasty polymer, and CT visibility was assessed. For ex vivo evaluation, bovine liver was injected with the polymer-loaded Lipiodol; for in vivo evaluation rats were injected subcutaneously with Lipiodol in polymer and CT was performed. We show that polymer diameter at CT correlates with implant weight and pathological measurements. Polymer formulation containing 5% Lipiodol was visible on CT in vitro. Ex vivo tests showed a round polymer deposit at the injection site compared with free dispersion of Lipiodol alone. Correlation between implant size at CT scan and surgery at 48 h was R(2) = 0.78. Average CT diameter at 9 days was 14.2 ± 2.8 mm in rats injected with Lipiodol in the polymer formulation, as compared with 7.3 ± 1.1 mm in controls. After 9 days, the implant degraded into several zones containing inflammatory cells seen on CT as areas with increased heterogeneity. In conclusion, Lipiodol incorporated in P(SA:RA) is visible on CT, and polymer degradation can potentially be monitored noninvasively. This method can be widely applied to follow changes in biodegradable implants.

Polymeric Nanostructures for Imaging and Therapy

“…Poly(sebacic- co -ricinoleic acid) with iodinated oil was used for implant visualization with CT and showed a possibility to trace changes in biodegradable implants. 181 …”

“…Nanosized CT contrast agents have been developed by many research groups to increase the sensitivity of CT imaging. , Among them are iodine-containing micelles, dendrimeric imaging agents, and nanoparticle- or polymer-based contrast agents comprised of gold (Au), , gadolinium (Gd), ytterbium (Yb), tantalum (Ta), or bismuth (Bi). − Iodinated oil, such as Lipiodol, is approved by the FDA for clinical imaging, and iodinated oil-containing polymeric nanoparticles have been developed with methoxy-terminated poly­(ethylene glycol)- block -poly­(ε-caprolactone) (mPEG- b -PCL). , Iodinated mPEG- b -PCL nanocapsules showed enhancement in contrast, improved blood persistence, and superior stability (up to 3 months in aqueous suspension). Poly­(sebacic- co -ricinoleic acid) with iodinated oil was used for implant visualization with CT and showed a possibility to trace changes in biodegradable implants …”

Injectable Biodegradable Multimodal Mammography Marker

“…Change in location or immediate decrease in the volume of the formulation is a sign of polymer migration, dissolution, or degradation in the body. This could potentially reduce the image quality of the formulation during scanning 35 or misguide a physician using the formulation for targeting a biopsy or treatment.…”

“…33 This unique gelation tendency in PSA:RA has been examined as implants that provide a controlled localized delivery system for paclitaxel and cisplatin. 34 Previously, we explored that the combination of PSA:RA with contrast agents such as lipiodol is clearly visible in CT. 35 We herein present a new PSA:RA based formulation that contains iodixanol and iron oxide contrast agents. Iodixanol is a nonionic hydrophilic contrast agent with diagnostic efficacy like that of other iodinated contrast media.…”

“…This unique gelation tendency in PSA:RA has been examined as implants that provide a controlled localized delivery system for paclitaxel and cisplatin . Previously, we explored that the combination of PSA:RA with contrast agents such as lipiodol is clearly visible in CT …”