Drug and cell encapsulation: alternative delivery options for the treatment of malignant brain tumors.
Malignant brain tumors including glioblastoma are incurable cancers. Over the last years a number of promising novel treatment approaches have been investigated including the application of inhibitors of receptor tyrosine kinases and downstream targets, immune-based therapies and anti-angiogenic agents. Unfortunately so far the major clinical trials in glioblastoma patients did not deliver clear clinical benefits. Systemic brain tumor therapy is seriously hampered by poor drug delivery to the brain. Although in glioblastoma, the blood brain barrier is disrupted in the tumor core, the major part of the tumor is largely protected by an intact blood brain barrier. Active cytotoxic compounds encapsulated into liposomes, micelles, and nanoparticles constitute novel treatment options because they can be designed to facilitate entry into the brain parenchyma. In the case of biological therapeutics, encapsulation of therapeutic cells and their implantation into the surgical cavity represents another promising approach. This technology provides long term release of the active compound at the tumor site and reduces side effects associated with systemic delivery. The proof of principle of encapsulated cell factories has been successfully demonstrated in experimental animal models and should pave the way for clinical application. Here we review the challenges associated with the treatment of brain tumors and the different encapsulation options available for drugs and living cells, with an emphasis on alginate based cell encapsulation technology.
NorLux Neuro-Oncology Laboratory, Department of Oncology, Centre de Recherche Public de la Santé (CRP-Santé), 84, Val Fleuri, L-1586 Luxembourg, Luxembourg; Department of Pathology and Medical Biology, Immunoendocrinology, University Medical Center Groningen, Hanzeplein 1, 9700 RB Groningen, The Netherlands. Electronic address: swapnil.bhujbal@crp-sante.lu.
Swapnil V
SV
Bhujbal
Department of Pathology and Medical Biology, Immunoendocrinology, University Medical Center Groningen, Hanzeplein 1, 9700 RB Groningen, The Netherlands. Electronic address: p.de.vos@umcg.nl.
Paul
P
de Vos
NorLux Neuro-Oncology Laboratory, Department of Oncology, Centre de Recherche Public de la Santé (CRP-Santé), 84, Val Fleuri, L-1586 Luxembourg, Luxembourg. Electronic address: simone.niclou@crp-sante.lu.
Simone P
SP
Niclou
D000818:Animals; D001812:Blood-Brain Barrier; D001932:Brain Neoplasms / Q000628:therapy*; D017690:Cell Transplantation; D016503:Drug Delivery Systems; D006801:Humans; D008081:Liposomes; D008823:Micelles; D053758:Nanoparticles
D008081:Liposomes; D008823:Micelles
Alginate; Drug delivery; Glioblastoma; Glioma; Liposome; Micelle; Microencapsulation; Nanoparticle; Therapeutic proteins