Anti-tumor and repairing nerve injuries: A drug-loaded monosialoganliosides micelles delivered to brain for glioblastoma

摘要

Introduction: Compared with clinical remission and extending life, quality of life in patients with glioblastoma have not been given enough attention in clinical treatment. Nerve injuries directly or indirectly effect on life of patients with glioblastoma. And the treatment of brain cancers remains great challenges because most of the therapeutic drugs can't be delivered to the tumors in the brain directly for the existence of blood-brain barrier (BBB) Therefore, we applied monosialoganglioside GM1 as drug-loaded nanosized carrier, which is amphiphilic molecules that spontaneously self-assemble into micelles. Moreover, GM1 is a kind of drug that can cross the BBB and treat neurological disease, exogenously administered GM1 have been proved to provoke regeneration and neurite outgrowth in the injured nervous system. The anti-tumor drugs can be encapsulated in self-assembled micelles of GM1 and are delivered to brain. Therefore, this drug delivery system has the capabilities of overcoming BBB, repairing nerve injuries, and eliminating tumor cells. Materials and Methods: Stock solution of DOX were prepared by dissolving the drug in dimethylsulfoxide (DMSO). Stock solution of purified monosialogangliosides GM1 were prepared by dissolving the gangliosides in tri-distilled water, and the solution were maintained at 4°C, they should be centrifuged and filtered prior to use. Stock solutions of DOX were slowly added to the solution of GM1 micelles. Then the mixed micelles were incubated at 4°C for 24h and dialyzed for 24h. The structure and morphology were characterized by TEM, and the mean diameter and its distribution were measured by means of Zetasizer. The method of DIR-loaded micelles is consistent with the preparation of mixed micelles of GM1 and DOX. Fluorescent micelles were injected intravenously in the caudal vein. Discussion and Conclusion: The morphology of micelles was detected using a JEM 1200EX transmission electron microscope. Fig A showed micelles GM1/DOX mixed micelles with about 20nm of mean diameter tends to evenly distributed. A normal mouse was injected with GM1/DIR micelles, distribution and intensity of DIR were monitored by In-Vivo FX PRO for small animal imaging. It revealed that GM1 can cross blood-brain barrier and target to brain because DIR were concentrated mainly in the brain tissue. (Fig.B).