Study: Localized delivery of chemo improves prognosis of recurrent glioblastoma

Researchers from Amrita University in India demonstrated that localized and sustained delivery of a chemotherapeutic agent in brain tumors can improve the prognosis of recurrent glioblastoma. The team’s work was published in Scientific Reports.

Although new drugs have been developed for glioblastoma multiforme, the overall survival rate for patients remains dismally low at 12 months, with a 3-year long term survival rate of 3% to 5%. Newly developed drugs face several delivery-related challenges, including poor drug accumulation in the brain tumor site and the inability to sustain adequate drug concentration in the tumor.

The team hypothesized that localizing and sustaining delivery of chemo drugs directly into the tumor for long periods of time without leakage into the peripheral blood could be ideal for treating patients with glioblastoma.

Arbor Pharmaceuticals’ Gliadel is the only FDA-approved intracranial drug delivery system and has been available in the clinic for the last 20 years. The microparticle implant delivers carmustine, an oncolytic agent, for 7 days and provides an improved survival advantage of more than 2 months. However, the Amrita University team noted that tumor recurrence has been reported in many of the patients treated with Gliadel, suggesting that the 7-day release may not be enough to stop tumor growth.

Many polymer-based systems loaded with cancer drugs such as doxorubicin and paclitaxel do not deliver drugs intracranially for more than 2 to 3 weeks, the researchers wrote.

The team developed a library of drug-loaded polyester nanofibers and electrospun them together, forming a 3D composite nanofiber implant capable of releasing the anti-glioma drug temozolomide continuously for 1 month into the brain tumor. The researchers optimized the implant’s nanofibers using in vivo brain drug release experiments, designing a composite implant formed from multiple nanofibers.

Then, the team co-electrospun suitable polymer-drug blends into a common target and formed a 3D wafer made of various nanofibers capable of releasing the drug for periods ranging from 1 day to 1 month. The authors tested 2 implants – TMZ-FR for 1 week release and TMZ-SR for 1 month release.

Animals implanted with the 1-month device had a long-term survival rate of 85.7%, compared to 54.6% in animals that received the 7-day implant. The team also noted that their wafers showed constant drug release with negligible leakage into the peripheral blood.

They concluded that this work underscores the importance of highly controlled, localized drug delivery to improve the prognosis for recurrent glioblastoma.