Intracranial MEMS based temozolomide delivery in a 9L rat gliosarcoma model

Byron C. Masi, Betty Mae Tyler, Hansen Bow, Robert T. Wicks, Yuan Xue, Henry Brem, Robert Langer, Michael J. Cima

Research output: Contribution to journalArticle

Abstract

Primary malignant brain tumors (BT) are the most common and aggressive malignant brain tumor. Treatment of BTs is a daunting task with median survival just at 21 months. Methods of localized delivery have achieved success in treating BT by circumventing the blood brain barrier and achieving high concentrations of therapeutic within the tumor. The capabilities of localized delivery can be enhanced by utilizing mirco-electro-mechanical systems (MEMS) technology to deliver drugs with precise temporal control over release kinetics. An intracranial MEMS based device was developed to deliver the clinically utilized chemotherapeutic temozolomide (TMZ) in a rodent glioma model. The device is a liquid crystalline polymer reservoir, capped by a MEMS microchip. The microchip contains three nitride membranes that can be independently ruptured at any point during or after implantation. The kinetics of TMZ release were validated and quantified in vitro. The safety of implanting the device intracranially was confirmed with preliminary in vivo studies. The impact of TMZ release kinetics was investigated by conducting in vivo studies that compared the effects of drug release rates and timing on animal survival. TMZ delivered from the device was effective at prolonging animal survival in a 9L rodent glioma model. Immunohistological analysis confirmed that TMZ was released in a viable, cytotoxic form. The results from the in vivo efficacy studies indicate that early, rapid delivery of TMZ from the device results in the most prolonged animal survival. The ability to actively control the rate and timing of drug(s) release holds tremendous potential for the treatment of BTs and related diseases.

Original languageEnglish (US)
Pages (from-to)5768-5775
Number of pages8
JournalBiomaterials
Volume33
Issue number23
DOIs
StatePublished - Aug 2012

Fingerprint

temozolomide
Gliosarcoma
Rats
Tumors
Brain
Animals
Brain Neoplasms
Kinetics
Equipment and Supplies
Glioma
Rodentia
Liquid crystal polymers
Nitrides
Pharmaceutical Preparations
Protective Devices
Blood-Brain Barrier
Membranes
Polymers
Technology

Keywords

  • Drug delivery
  • Glioma
  • Localized delivery
  • MEMS
  • Microchip
  • Temozolomide

ASJC Scopus subject areas

  • Biomaterials
  • Bioengineering
  • Ceramics and Composites
  • Mechanics of Materials
  • Biophysics

Cite this

Intracranial MEMS based temozolomide delivery in a 9L rat gliosarcoma model. / Masi, Byron C.; Tyler, Betty Mae; Bow, Hansen; Wicks, Robert T.; Xue, Yuan; Brem, Henry; Langer, Robert; Cima, Michael J.

In: Biomaterials, Vol. 33, No. 23, 08.2012, p. 5768-5775.

Research output: Contribution to journalArticle

Masi, Byron C. ; Tyler, Betty Mae ; Bow, Hansen ; Wicks, Robert T. ; Xue, Yuan ; Brem, Henry ; Langer, Robert ; Cima, Michael J. / Intracranial MEMS based temozolomide delivery in a 9L rat gliosarcoma model. In: Biomaterials. 2012 ; Vol. 33, No. 23. pp. 5768-5775.
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