P10.03.B Insights into the development of tunable brain implants for local chemotherapy

Abstract

Abstract Background Glioblastomas (GBMs) remain an unmastered medical challenge. Poor delivery and systemic toxicity of many chemotherapeutic agents limit their therapeutic success in GBM treatment. Bioelectronic implants for local chemo drug delivery can optimize drug concentrations at the tumor site, duration of treatment and tumor suppression, while systemic effects remain at an acceptable low level. We present miniature bioelectronic devices for drug delivery able to administer chemotherapeutics via electric control with high spatiotemporal precision.1 The drug delivery is based on the electro migration of drug molecules in an ion selective matrix towards a target of choice. These bioelectronic devices, called chemotherapeutic ion pumps (chemoIPs), can be used for triggered drug release of chemotherapeutics that are usually shielded by the blood brain barrier. Material and Methods The performance of chemoIPs is studied in different brain tumor models with increasing complexity (cell culture and different in vivo models). With chemoIPs it is possible to constantly administer drugs with highest precision (delivery rates at pmol*min-1 precision) towards cell culture spheroids, ex ovo-grown tumors and in vivo brain tumors Results The treatment efficiency was analyzed via flow cytometry quantifying apoptosis and cell cycle arrest, as well as immune-histochemical analysis for apoptosis. ChemoIP treatment is able to trigger the disintegration of targeted tumor spheroids, and is able to inhibit the tumor growth of ex ovo-grown glioblastomas significantly. Furthermore, the proteomes of neurons and glioblastoma cells were recorded via proteomics, which showed that only GBM cells are harmed by the chemotherapeutic treatment, but not neurons. In parallel, can follow the pharmacokinetics of the chemoIP-mediated drug administration via drug quantification using mass spectrometry and compare it to computer simulations in different tumor models. Conclusion The here exemplified electrically-driven drug delivery via chemoIPs is a drug administration method that can serve as basis for further implant development, which has the potential to increase the efficacy of chemotherapy due to highly-targeted and locally-controlled drug delivery.