Long acting carmustine loaded natural extracellular matrix hydrogel for inhibition of glioblastoma recurrence after tumor resection

Abstract

Many scientific efforts have been made to penetrate the blood-brain barrier and target glioblastoma cells, but the outcomes have been limited. More attention should be given to local inhibition of recurrence after glioblastoma resection to meet real medical needs. A biodegradable wafer containing the chemotherapeutics carmustine (1,3-bis(2-chloroethyl)-1-nitrosourea, BCNU) was the only local drug delivery system approved for clinical glioblastoma treatment, but with a prolonged survival time of only two months and frequent side effects. In this study, to improve the sustained release and prolonged therapeutic effect of drugs for inhibiting tumor recurrence after tumor resection, both free BCNU and BCNU- poly (lactic-co-glycolic acid) (the ratio of lactic acid groups to glycolic acid groups is 75/25) nanoparticles were simultaneously loaded into natural extracellular matrix hydrogel from pigskin to prepare BCNU gels. The hydrogel was injected into the resection cavity of a glioblastoma tumor immediately after tumor removal in a fully characterized resection rat model. Free drugs were released instantly to kill the residual tumor cells, while drugs in nanoparticles were continuously released to achieve a continuous and effective inhibition of the residual tumor cells for 30 days. These combined actions effectively restricted tumor growth in rats. Thus, this strategy of local drug implantation and delivery may provide a reliable method to inhibit the recurrence of glioblastoma after tumor resection in vivo.

Graphical abstract

Keywords

BCNU / glioblastoma recurrence / tumor resection / nanoparticles / hydrogel

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Acknowledgements

This work was partially supported by the National Natural Science Foundation of China (Grant Nos. 82074277 and 8177391), the Basic Research Cooperation Project of Beijing, Tianjin, Hebei from the Natural Science Foundation of Tianjin (Grant Nos. 20JCZXJC00070 and J200018), and the Young Elite Scientists Sponsorship Program of Tianjin (Grant No. TJSQNTJ-2017-14).

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