In vivo drug distribution dynamics in thermoablated and normal rabbit livers from biodegradable polymers

Abstract

Image-guided radiofrequency ablation combined with intratumoral drug delivery provides a novel and minimally invasive treatment of liver cancers. In this study, the in vivo transport properties of doxorubicin in thermoablated and nonablated rabbit livers were characterized and compared. Doxorubicin was released from polymer implants (millirods) to the ablated and nonablated liver tissue. At different time points, the 2D distribution profiles were quantitatively determined by a fluorescence imaging method. Analysis of the doxorubicin concentration at the ablation boundary showed that it reached a maximum of 49.8 microg/g at 24 h after implantation, which was higher than the reported cytotoxic concentration of doxorubicin (6.4 microg/g) for liver VX-2 cancer cells. This value dropped to 0.4 microg/g at 48 h after implantation due to the depletion of doxorubicin from the polymer millirod. Results also showed that the area of drug distribution was significantly larger in ablated tissue than nonablated tissue. The therapeutic penetration distance was found to be 5.2 mm in thermoablated livers, compared to 1.2 mm in nonablated livers at 24 h. This difference in drug transport properties is attributed to destruction of the vasculature network in the ablated tissue as supported by histological analysis. Consequently, drug washout by blood perfusion is hampered while drug diffusion becomes the dominant process of transport in the ablated tissue. Results from this study provide insightful information on the rational design and development of polymer millirods for intratumoral drug delivery applications.

Local drug delivery strategies for cancer treatment: Gels, nanoparticles, polymeric films, rods, and wafers

“…Tumor recurrence is greatest at the periphery of the ablation zone and around blood vessels where residual tumor cells remain. It is hypothesized that drug eluted from an implant placed at the center of an ablation region will undergo enhanced tissue penetration, in part due to destroyed tumor vasculature in the ablated region [88]. The Gao group developed drug-loaded poly(lactide-co-glycolide) polymer millirods to prevent recurrence in thermoablated tissues through image-guided delivery via a 14 gauge biopsy needle [89].…”

New Aspects in Sustained Drug Release Formulations

“…A double layer dual-release device provides an initial loading dosage followed by a maintenance dosage to a specific area [145]. Such a device is a reservoir-type system, wherein the outer layer is a film or membrane containing a drug, such as an anticancer agent, while the inner layer or core is a monolithic mixture of the drug.…”

Species and Density of Implant Surface Chemistry Affect the Extent of Foreign Body Reactions

“…For example, subcutaneous implants delivering contraceptives, chemotherapeutic drugs and insulin were widely used in the past. [1][2][3][4][5][6][7][8] In addition to having a simple implantation procedure, they also relieve the patient from being hospitalized and/or receiving frequent painful injections. 9 However, many of these medical devices fail to produce long term therapeutic effect raising serious concerns over the efficiency of these implants.…”