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Polymer Implants for Intratumoral Drug Delivery and Cancer Therapy

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Abstract

To address the need for minimally invasive treatment of unresectable tumors, intratumoral polymer implants have been developed to release a variety of chemotherapeutic agents for the locoregional therapy of cancer. These implants, also termed “polymer millirods,” were designed to provide optimal drug release kinetics to improve drug delivery efficiency and antitumor efficacy when treating unresectable tumors. Modeling of drug transport properties in different tissue environments has provided theoretical insights on rational implant design, and several imaging techniques have been established to monitor the local drug concentrations surrounding these implants both ex vivo and in vivo. Preliminary antitumor efficacy and drug distribution studies in a rabbit liver tumor model have shown that these implants can restrict tumor growth in small animal tumors (diameter <1 cm). In the future, new approaches, such as three‐dimensional (3‐D) drug distribution modeling and the use of multiple drug‐releasing implants, will be used to extend the efficacy of these implants in treating larger tumors more similar to intractable human tumors.

Section snippets

INTRODUCTION

Cancer is an enormous health concern in the United States and in recent years has surpassed heart disease as the predominant cause of death for all but the most elderly Americans.1 Currently, the most curative treatment option for solid tumors is surgical resection followed by adjuvant chemotherapy or radiation therapy to minimize the risk of recurrence. Many cancers respond well to this treatment strategy, but many patients are not eligible for surgical resection. For example, out of 70000

Definition of Pharmacokinetic Goals for Local Drug Delivery to Unresectable Tumors

In considering the use of an intratumoral implant for tumor treatment, it is necessary to consider the generic characteristics that would benefit the device. First, the implant should be able to minimize shortcomings associated with systemically administered chemotherapy. Second, it should provide an optimal drug delivery profile to the tumor, which is to say that it should be able to provide effective drug concentrations to the desired region over a prolonged period of time. Third, the device

Overview of Methods to Investigate Local Drug Release and Tissue Distribution

In developing an intratumoral chemotherapy device, techniques for monitoring local drug concentrations are necessary to optimize implant design. Measuring drug concentration as a function of time provides a quantitative method to compare multiple treatments. Many different techniques can be used to monitor drug release from intratumoral implants. While certain techniques require extraction of tissue and measurement of drug concentration ex vivo, alternate, noninvasive imaging based‐techniques

Drug Distribution and Antitumor Efficacy from Liver Tumor Treatment with Polymer Implants

After extensive pharmacokinetic study of polymer millirods in normal livers, preliminary studies of drug distribution and treatment efficacy in tumor tissue were performed. One study assessed the use of implants alone for treatment and local control of small liver tumors;66 the second study explored drug distribution and therapeutic effects of an approach combining RF ablation followed by implant placement.67 Both of these studies were performed using the rabbit VX2 model of liver carcinoma,

CONCLUSIONS AND FUTURE OUTLOOK

Conventional systemic chemotherapy for tumors is restricted by lack of tumor specificity and severe side effects associated with intrinsic drug toxicity.5., 6., 7. With the emergence of minimally invasive, image‐guided interventional technology, tumor chemotherapy is at the threshold of a major breakthrough because of such technological advances in targeting strategies that overcome the previous limitations. Tumor‐directed therapies, such as focal ablation and locoregional chemotherapy, are

Acknowledgements

This work was supported by the NIH grant R01 CA090696 to JG. BW is supported by a DOD predoctoral fellowship BC043453 and the NIH grant T32 GM07250 to the Case Western Reserve University Medical Scientist Training Program. EB is supported by a NIH minority supplement. This is manuscript CSCNP009 from the “Cell Stress and Cancer Nanomedicine” program in the Simmons Comprehensive Cancer Center at UT Southwestern Medical Center at Dallas.

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