Role of Polymeric Local Drug Delivery in Multimodal Treatment of Malignant Glioma: A Review

Abstract

Malignant gliomas (MGs) are the most common and devastating primary brain tumor. At present, surgical interventions, radiotherapy, and chemotherapy are only marginally effective in prolonging the life expectancy of patients with MGs. Inherent heterogeneity, aggressive invasion and infiltration, intact physical barriers, and the numerous mechanisms underlying chemotherapy and radiotherapy resistance contribute to the poor prognosis for patients with MGs. Various studies have investigated methods to overcome these obstacles in MG treatment. In this review, we address difficulties in MG treatment and focus on promising polymeric local drug delivery systems. In contrast to most local delivery systems, which are directly implanted into the residual cavity after intratumoral injection or the surgical removal of a tumor, some rapidly developing and promising nanotechnological methodsincluding surface-decorated nanoparticles, magnetic nanoparticles, and focused ultrasound assist transport-are administered through (systemic) intravascular injection. We also discuss further synergistic and multimodal strategies for heightening therapeutic efficacy. Finally, we outline the challenges and therapeutic potential of these polymeric drug delivery systems.

Applying Synthetic Biology with Rational Design to Nature’s Greatest Challenges: Bioengineering Immunotherapeutics for the Treatment of Glioblastoma

“…Polymeric structures importantly allow for local and/or sustained release of active therapeutics and have been long a subject of investigation in gliomas, particularly as implants in the post-resection cavity [45][46][47][48][49][50][51][52][53][54]. BCNU wafers were approved for local delivery of carmustine to the glioma resection cavity in 1996, leading the pack on implantable local therapeutics for brain tumors [55,56].…”

Bacteria loaded with glucose polymer and photosensitive ICG silicon-nanoparticles for glioblastoma photothermal immunotherapy

“…Among these non-invasive strategies, the nanoparticulate drug delivery systems have shown promising clinical value in GBM therapy due to their appealing properties such as high drug loading efficiency, spatial- and temporal-controlled drug release, real-time visualization during the therapeutic process and so forth 18 – 26 . Despite these elegant works, there are still no clinically approved nanoparticle-based therapies against GBM owing to the following hurdles: (1) the intrinsic properties of nanoparticles such as size, surface charge, and opsonization can influence uptake of them into phagocytes, thereby preventing their entry into the brain; (2) the premature release of payload might occur during systemic circulation since therapeutic agents are generally loaded on nanoparticles through charge interaction or hydrophobic interaction; (3) the nanoparticles even crossing BBB still hardly penetrate deeply into GBM tissues owing to the high interstitial fluid pressure of GBM tissues, thus hampering their therapeutic effects 5 , 15 , 27 , 28 .…”

Supramolecular Hydrogel Based Post-Surgical Implant System for Hydrophobic Drug Delivery Against Glioma Recurrence

“…Polymer-based local delivery systems must have attributes such as high drug-loading capacity, low volume requirement, biocompatibility, biodegradability, good conformity, and efficiency in co-delivery of chemotherapy agents. 12 Polyethyleneglycol-polycaprolactone based co-polymer combinations have been widely reported for biomedical and nanomedicine applications in the form of nanoparticles, micelles, and hydrogels. 13 It is a biocompatible drug delivery system with reported applications in theranostics, nucleic acid, plasmid delivery, passive and targeted delivery of chemotherapeutic drugs, cytokines, growth factors, etc.…”