Local Drug Delivery Strategies for Glioblastoma Treatment

Abstract

Glioblastoma multiforme (GBM) is a brain tumor notorious for its malignancy. The key reason for the limited efficacy of standard treatment is the high recurrence rate of GBM, even after surgical resection. Hence, intensive postsurgical chemical therapies, such as the systemic delivery of various drugs and/or drug combinations, are typically followed after surgery. However, overcoming the blood-brain barrier by systemic administration to efficiently deliver drugs to the brain tumor remains a daunting goal. Therefore, various local drug delivery methods showing potential for improved therapeutic efficacy have been proposed. In particular, the recent application of electronic devices for the controlled delivery of chemotherapy drugs to GBM tissue has attracted attention. We herein review the recent progress of local drug delivery strategies, including electronics-assisted strategies, at the research and commercial level. We also present a brief discussion of the unsolved challenges and future research direction of localized chemotherapy methods for GBM.

Keywords: Absorbable implants; Blood-brain barrier; Brain tumor; Chemotherapy; Drug administration routes; Drug delivery systems.

Fig. 1. Local drug delivery strategies. A: Schematic illustration of convection enhanced drug delivery compared to the normal diffusion method. B: Schematic illustration of the structure of the liposomal doxorubicin. C: Optical image of the Gliadel wafer implanted on the cavity after resection. D: Schematic illustration of the Ommaya reservoir implanted into the brain. E: Optical image of a nanofiber wafer implanted on the brain. F: Schematic illustration of the administration of the therapeutic nanoparticles conjugated with targeting moieties for the glioblastoma multiforme treatment. G: Optical image of the GemC12-lipid nanocapsules hydrogel implanted on the cavity after resection. H: Schematic illustration and optical image (inset) of the tumor-guiding conduit implanted on the tumor tissue in the brain. I: Schematic illustration of the delivery of theranostic nanoparticles (NPs) using bioresorbable microneedles (MNs). J: Schematic illustration of the delivery of the high-energy photons using light-guiding microneedles with microparticles (MPs), light-emitting diode (LED), and bioelectronics. K: Schematic illustration of drug delivery by the bioresorbable electronic patch (BEP) with magnetic actuation. L: Optical image of tumor tissues without (left) and with (right) the magnetic actuation. A: Adapted from Pena et al. Int J Mol Sci 2021;22:13160 [38]; B: Adapted from Ibrahim et al. Pharmaceutics 2022;14: 254 [40]; C: Adapted from Kleinberg. Patient Prefer Adherence 2016;10:2397-406 [42]; D: Adapted from Lau et al. Cureus 2012;4:e66 [43]; E: Adapted from Ramachandran et al. Sci Rep 2017;7:43271 [48]; F: Adapted from Meng et al. Nat Commun 2020;11:594 [50]; G: Adapted from Shi et al. Sci Rep 2016;6:19077 [52]; K and L: Adapted from Lee et al. Nat Commun 2019;15;10:5205 [58]; under the Creative Commons license. I and J: Adapted from Lee et al. Adv Mater 2021;33:2100425, with permission from John Wiley and Sons [57].