Still, its efficacy is strongly limited by innate or acquired resistance of glioma cells to this drug 4 as well as by an only limited ability to pass the blood–brain barrier (BBB) 5. Temozolomide (TMZ), a methyl-alkylating pro-drug causing mismatch during cell DNA repair mechanism, is the chemotherapeutic agent exhibiting the best clinical performance in GBM and, therefore, represents the Food and Drug administration (FDA)-approved first line chemotherapy intervention for these tumors 3. The extremely difficult possibility of complete removal by surgery makes radiotherapy and chemotherapy key adjuvating approaches for tumor treatment 3. It has an incidence rate of around 2–3 over 100.000 persons in the population of developed countries, and a 5-year survival rate of approximately 5% 2. Glioblastoma multiforme (GBM) is the most aggressive primary tumor of the central nervous system 1. 2-TMZ and are therefore new promising gel-based local therapy candidates for the treatment of GBM. When applied intracranially to a resected U87-MG-Red-FLuc human GBM model, 2-TMZ and caused a significant reduction in the growth of tumor recurrences, when compared to untreated controls. The two newly designed anticancer formulations, consisting in TMZ-silica (SiO dispersed in the thermogel matrix 2-TMZ) and TMZ, spray-dried on PLC and incorporated into the thermogel induced cell death in vitro. Next, we loaded TMZ into such matrices 2-TMZ and and tested their therapeutic potential both in vitro and in vivo, in a glioblastoma resection and recurrence mouse model based on orthotopic growth of human cancer cells. The biocompatibility of a chitosan-β-glycerophosphate-based thermogel (THG)-containing mesoporous SiO 2 nanoparticles 2) or polycaprolactone microparticles was ascertained in vitro and in vivo by cell counting and histological examination.
Here, we aimed at designing new negative temperature-responsive gel formulations able to locally release TMZ beyond the BBB. While Temozolomide (TMZ) exhibits the best clinical performance, still less than 20% crosses the BBB, therefore requiring administration of very high doses with resulting unnecessary systemic side effects. GBM pharmacological treatment is strongly limited by its intracranial location beyond the blood–brain barrier (BBB). Glioblastoma multiforme (GBM) is the most aggressive primary tumor of the central nervous system and the diagnosis is often dismal.
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