Abstract
Effective treatment for glioblastoma (GBM) will likely require targeted delivery of several specific pharmacological agents simultaneously. Intra-arterial (IA) delivery is one technique for targeting the tumor site with multiple agents. Although IA chemotherapy for glioblastoma (GBM) has been attempted since the 1950s, the predicted benefits remain unproven in clinical practice. This review focuses on innovative approaches to IA drug delivery in treating GBM. Guided by novel in vitro and in vivo optical measurements, newer pharmacokinetic models promise to better define the complex relationship between background cerebral blood flow and drug injection parameters. Advanced optical technologies and tracers, unique nanoparticles designs, new cellular targets, and rational drug formulations are continuously modifying the therapeutic landscape for GBM. Personalized treatment approaches are emerging; however, such tailored approaches will largely depend on effective drug delivery techniques and on the ability to simultaneously deliver multidrug regimens. These new paradigms for tumor-selective drug delivery herald dramatic improvements in the effectiveness of IA chemotherapy for GBM. Therefore, within this context of so-called “precision medicine,” the role of IA delivery for GBM is thoroughly reassessed.
Highlights
Drugs directed against glioblastoma may be delivered by a number of routes, from a physiological standpoint, intra-arterial (IA) drug delivery is an appealing method (Table 1) [1]
The key to effective IA drug delivery lies in proper drug selection as well as in optimizing the delivery technique based on specific controllable parameters (Figure 2)
Another novel alternative is immunoliposomes, nonspecifically targeted to the vascular endothelium (CD 31, ACE, or Factor VIII/vWF-Ag), to the transport systems (OX-26 antibody to transferrin receptor), or to the pathology specific antigens (ICAMs) [125,126,127,128]. Immunoconjugated drugs, such as OX26-methotrexate and OX26-daunorubicin, chimeric drugs using high capacity transporter systems, or drugs with exceedingly brief duration of actions that are hydrolyzed during transit through cerebral/regional circulation by ubiquitous enzymes, such as esterases or alkaline phosphatases, are intriguing options that should be considered for IA delivery [128]
Summary
Drugs directed against glioblastoma may be delivered by a number of routes, from a physiological standpoint, intra-arterial (IA) drug delivery is an appealing method (Table 1) [1]. IA drugs have been widely used in recent years, either off-label or as part of clinical trials [14, 17,18,19,20,21,22,23,24,25,26] Most of these attempts rely on the general belief that local injections, transiently generating high arterial blood concentrations, will lead to the desired pharmacodynamic effects. Emerging optical technologies offer novel insight into the complex pharmacokinetics of IA drug delivery and may lead to improved clinical effectiveness [40,41,42,43]. We believe that the insights provided by these novel technologies will improve drug targeting while significantly minimizing complications that have plagued the field in the past
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
