The use of TMZ embedded hydrogels for the treatment of orthotopic human glioma xenografts

Bandita Adhikari; Jie Li; Michael G Brandel; Diahnn Futalan; Johnny Akers; Timothy Deming; Clark C Chen; Bob S Carter

doi:10.1016/j.jocn.2017.07.027

The use of TMZ embedded hydrogels for the treatment of orthotopic human glioma xenografts

J Clin Neurosci. 2017 Nov:45:288-292. doi: 10.1016/j.jocn.2017.07.027. Epub 2017 Sep 1.

Authors

Bandita Adhikari¹, Jie Li², Michael G Brandel³, Diahnn Futalan⁴, Johnny Akers⁵, Timothy Deming⁶, Clark C Chen⁷, Bob S Carter⁸

Affiliations

¹ Center for Theoretical and Applied Neuro-Oncology, Moores Cancer Center, Division of Neurosurgery, University of California San Diego, La Jolla, CA 92093, USA. Electronic address: [email protected].
² Center for Theoretical and Applied Neuro-Oncology, Moores Cancer Center, Division of Neurosurgery, University of California San Diego, La Jolla, CA 92093, USA. Electronic address: [email protected].
³ Center for Theoretical and Applied Neuro-Oncology, Moores Cancer Center, Division of Neurosurgery, University of California San Diego, La Jolla, CA 92093, USA. Electronic address: [email protected].
⁴ Center for Theoretical and Applied Neuro-Oncology, Moores Cancer Center, Division of Neurosurgery, University of California San Diego, La Jolla, CA 92093, USA. Electronic address: [email protected].
⁵ Center for Theoretical and Applied Neuro-Oncology, Moores Cancer Center, Division of Neurosurgery, University of California San Diego, La Jolla, CA 92093, USA. Electronic address: [email protected].
⁶ Department of Bioengineering, University of California Los Angeles, Los Angeles, CA 90095-1600, USA; Department of Chemistry and Biochemistry, University of California Los Angeles, Los Angeles, CA 90095-1600, USA. Electronic address: [email protected].
⁷ Center for Theoretical and Applied Neuro-Oncology, Moores Cancer Center, Division of Neurosurgery, University of California San Diego, La Jolla, CA 92093, USA; Department of Neurosurgery, University of Minnesota, Minneapolis, MN 55455, USA. Electronic address: [email protected].
⁸ Center for Theoretical and Applied Neuro-Oncology, Moores Cancer Center, Division of Neurosurgery, University of California San Diego, La Jolla, CA 92093, USA. Electronic address: [email protected].

PMID: 28867360
DOI: 10.1016/j.jocn.2017.07.027

Abstract

The current treatment of glioblastoma multiforme (GBM) is limited by the restricted arsenal of agents which effectively cross the blood brain barrier (BBB). For example, only a fraction of temozolomide (TMZ) administered systemically is available for therapeutic effect because of the BBB and the instability of TMZ under physiologic conditions. A novel approach to overcome this obstacle is to bypass the BBB and locally deliver chemotherapeutic agents directly to the tumor mass. We have explored the loading of TMZ into a novel hydrogel matrix, which can be delivered in liquid form and then solidifies in situ and releases chemotherapy as the matrix dissolves. Here, we tested the effect of amphiphilic diblock copolypeptide hydrogels (DCHs) of 180-poly-lysine and 20-poly-leucine (K₁₈₀L₂₀) on TMZ using Glioblastoma models. In both the in vitro model, which involved treatment of a human glioblastoma GSC line suspended as neurospheres, and in vivo using an orthotopic glioma xenograft mouse model, we found that K₁₈₀L₂₀ could safely enhance the efficacy of TMZ. This technique may offer the opportunity to 'coat' the inner lining of the cavity following glioma resection with a slow-release TMZ and potentially decrease recurrence. Future studies in larger animals are needed to delineate this effect.

Keywords: Glioma; Hydrogel; TMZ.

MeSH terms

Animals
Antineoplastic Agents / therapeutic use
Brain Neoplasms / drug therapy*
Cell Line, Tumor
Dacarbazine / administration & dosage
Dacarbazine / analogs & derivatives*
Dacarbazine / chemistry
Dacarbazine / therapeutic use
Disease Models, Animal
Glioblastoma / drug therapy*
Glioma / drug therapy*
Humans
Hydrogels / administration & dosage*
Hydrogels / chemistry
Mice
Neoplasm Recurrence, Local / drug therapy
Temozolomide
Xenograft Model Antitumor Assays

Substances

Antineoplastic Agents
Hydrogels
Dacarbazine
Temozolomide