Drug Delivery Nanosystems in Glioblastoma Multiforme Treatment: Current State of the Art

Abstract

: Glioblastoma multiforme (GBM) is the most common primary malignant Central Nervous System cancer, responsible for about 4% of all deaths associated with neoplasia, characterized as one of the most fatal human cancers. Tumor resection does not possess curative character, thereby radio and/or chemotherapy are often necessary for the treatment of GBM. However, drugs used in GBM chemotherapy present some limitations, such as side effects associated with nonspecific drug biodistribution as well as limited bioavailability, which limits their clinical use. To attenuate the systemic toxicity and overcome the poor bioavailability, a very attractive approach is drug encapsulation in drug delivery nanosystems. The main focus of this review is to explore the actual cancer global problem, enunciate barriers to overcome in the pharmacological treatment of GBM, as well as the most updated drug delivery nanosystems for GBM treatment and how they influence biopharmaceutical properties of anti-GBM drugs. The discussion will approach lipid-based and polymeric nanosystems, as well as inorganic nanoparticles, regarding their technical aspects as well as biological effects in GBM treatment. Furthermore, the current state of the art, challenges to overcome and future perspectives in GBM treatment will be discussed.

Glioblastoma Therapy: Past, Present and Future

“…Invasive (local administration) and noninvasive tools to deliver drugs are continuously evolving to overcome the BBB [ 23 ]. As reviewed in previous works [ 884 , 885 , 886 , 887 ], several nanostructures, including polymeric nanoparticles (NPs) (e.g., dendrimers, polymer micelles or nanospheres), inorganic NPs (e.g., silica, iron, gold or graphene NPs), lipid-based NPs (e.g., liposomes, emulsions), nanogels, carbon dots and nano-implants, have been developed as drug delivery systems and potential diagnostic agents for GB over the past decades. These elements can contain active anti-GB agents, such as chemotherapeutic/anti-angiogenic drugs, radio or chemosensitizers, or immune cells along with moieties that specifically target GB cellular receptors/angiogenic blood vessels or facilitate opening of the BBB [ 888 , 889 ].…”

Combinatorial chemotherapy via poloxamer 188 surface-modified PLGA nanoparticles that traverse the blood-brain-barrier in a glioblastoma model

“…MTX molecular weight is ~454 g/mol with a logP of ~-1.8 which demonstrates its tendency to dissolve in water than hydrophobic solvents [25] therefore the efficient BBB entrance of MTX is declined [30]. The effectiveness of MTX in GBM treatment has been proven in the clinic [11], but untargeted toxicity resulting from the systemic distribution of MTX is still an unsolved obstacle to its use [31].…”

Recent Advances on Surface-Modified GBM Targeted Nanoparticles: Targeting Strategies and Surface Characterization

“…In this framework, the application of NPs in the medical field, known as nanomedicine, has opened new opportunities for the treatment of hard-to-treat diseases, e.g., neurodegenerative or genetic diseases, especially GBM [10,11]. Several NPs have been tested to encapsulate traditional drugs in order to enhance drug solubility, encapsulation, and protection in the biological environment, reduce off-target toxicity, and enable passage through the BBB and/or the specific delivery of drugs to GBM via targeting, as well as controlled release at the target site [12][13][14][15][16][17][18][19][20][21][22][23]. The possibility of engineering the surface of NPs with molecules that can promote specific accumulation in the brain or in GBM cells has opened the way toward highly effective treatment options.…”