ABSTRACT
Novel approaches to achieve local, intratumoral drug delivery have the dual benefit of reducing systemic toxicity while enhancing efficacy for malignant cells. We have developed a new implantable system combining a next-generation BioNEMS nanofluidic membrane with parallel nanochannels that offers controlled release of biomolecules. Based on concentration-driven diffusive transport, nanochannel membranes provide a "drug agnostic" delivery mechanism. Integrating this nanotechnology within a small implantable capsule permits multipurpose functionality and compatibility with different therapeutic approaches as well as diagnostic imaging capability. A minimally-invasive, percutaneous trocar delivery mechanism enables serial implantation throughout a target tissue volume. In this manuscript, we demonstrate that this platform is capable of sustained delivery for chemotherapy, radiosensitization, immunomodulation, and imaging contrast, among others. This platform's utility was established through release of doxorubicin, OX86, FGK45, and Magnevist. Further proof-of-concept experiments demonstrated successful in vivo implantation and intratumoral release of antibodies and contrast agents, as well as the platform's MR-compatibility and capability as a radiopaque fiducial. These results provide strong evidence for a flexible, multifunctional nanofluidic implant capable of broadening local delivery utility in the clinic.
