Model simulation and experimental validation of intratumoral chemotherapy using multiple polymer implants

Abstract

Radiofrequency ablation has emerged as a minimally invasive option for liver cancer treatment, but local tumor recurrence is common. To eliminate residual tumor cells in the ablated tumor, biodegradable polymer millirods have been designed for local drug (e.g., doxorubicin) delivery. A limitation of this method has been the extent of drug penetration into the tumor (< 5 mm), especially in the peripheral tumor rim where thermal ablation is less effective. To provide drug concentration above the therapeutic level as needed throughout a large tumor, implant strategies with multiple millirods were devised using a computational model. This dynamic, 3-D mass balance model of drug distribution in tissue was used to simulate the consequences of various numbers of implants in different locations. Experimental testing of model predictions was performed in a rabbit VX2 carcinoma model. This study demonstrates the value of multiple implants to provide therapeutic drug levels in large ablated tumors.

Ultrasound-Guided Intratumoral Delivery of Doxorubicin from in Situ Forming Implants in a Hepatocellular Carcinoma Model

“…These release kinetics provide a means for rapidly achieving a therapeutic dose, followed by lower daily maintenance doses released by the implant [21,23,56]. Polymer millirods, which follow a similar release profile, have shown promise as a local delivery system for treating ectopic lesions [24,25].…”

“…While local therapy was not more effective at reducing tumor volume, it did effectively reduce systemic exposure. In this study a single implant was injected into the center of the lesion, while a potentially more effective approach would be to uniformly inject small implants throughout the tumor volume to ensure homogenous distribution of the drug throughout the entire tumor volume [25].…”

“…Alternatively, intratumoral drug delivery provides a promising means by which drugs can be administered directly into the lesion, while minimizing systemic exposure. Local doxorubicin delivery has been achieved through the use of drug-loaded polymer millirods and implants, which can be placed within a lesion in a minimally invasive manner, and have been shown to facilitate elevated drug concentrations throughout the tumor volume [23][24][25][26].…”

Preparation of self-solidifying polymeric depots from PLEC-PEG-PLEC triblock copolymers as an injectable drug delivery system

“…These systems also have relatively less complicated manufacturing procedures providing the ease of preparation. Moreover, the in situ solidification process lead to the ease of administration allowing the multiple injections throughout the area of interest [9]. Therefore, these drug delivery systems can be used as platforms for pharmaceutical applications.…”

Interventional navigation systems for treatment of unresectable liver tumor

“…However, a number of local treatment methods for effective tumor destruction of unresectable liver tumors have recently received considerable interests. The procedures include cryoablation (CA) [19], radiofrequency ablation (RFA) [8], ethanol injection therapy (PEIT) [23], intratumoral chemotherapy [29], highintensity focused ultrasound (HIFU) [5], laser [28], and microwave ablation [9,15]. The major task of these therapeutic procedures is accurate needle placement according to pre-operative planning data, with the aim of complete removal of tumor and minimal damage to surrounding normal liver parenchyma.…”