2-(2-Methoxyphenyl)-3-((Piperidin-1-yl)ethyl)thiazolidin-4-One-Loaded Polymeric Nanocapsules: In Vitro Antiglioma Activity and In Vivo Toxicity Evaluation

• Published in: Cellular and molecular neurobiology 2019-08, Vol.39 (6), p.783-797
• Main Authors: da Silveira, Elita Ferreira, Ferreira, Luana Mota, Gehrcke, Mailine, Cruz, Letícia, Pedra, Nathália Stark, Ramos, Priscila Treptow, Bona, Natália Pontes, Soares, Mayara Sandrielly Pereira, Rodrigues, Rodrigo, Spanevello, Rosélia Maria, Cunico, Wilson, Stefanello, Francieli M., Azambuja, Juliana Hofstatter, Horn, Ana Paula, Braganhol, Elizandra
• Format: Article
• Language: English
• Subjects: Angiogenesis; Animals; Antioxidants; Apoptosis - drug effects; Astrocytes; Astrocytes - drug effects; Astrocytes - metabolism; Astrocytes - pathology; Biodegradability; Biomarkers, Tumor - blood; Biomedical and Life Sciences; Biomedicine; Brain - drug effects; Brain - pathology; Brain cancer; Brain Neoplasms - blood; Brain Neoplasms - drug therapy; Brain Neoplasms - pathology; Brain tumors; Cell Biology; Cell Line, Tumor; Cell Proliferation - drug effects; Cell Survival - drug effects; Drug delivery; Drug Liberation; Glioblastoma; Glioma - blood; Glioma - drug therapy; Glioma - pathology; Humans; Inflammation; Light; Liver - drug effects; Liver - pathology; Male; Metastases; Nanocapsules - chemistry; Neurobiology; Neurosciences; Original Research; Oxidative Stress - drug effects; Piperidines - chemical synthesis; Piperidines - chemistry; Piperidines - therapeutic use; Piperidines - toxicity; Polymers; Polymers - chemical synthesis; Polymers - chemistry; Radioresistance; Rats, Wistar; Thiazolidines - chemical synthesis; Thiazolidines - chemistry; Thiazolidines - therapeutic use; Thiazolidines - toxicity; Thiobarbituric Acid Reactive Substances - metabolism; Toxicity; Toxicity Tests; Weight Loss - drug effects; Zeta potential
• ISSN: 0272-4340; 1573-6830; 1573-6830
• DOI: 10.1007/s10571-019-00678-4

Among gliomas types, glioblastoma is considered the most malignant and the worst form of primary brain tumor. It is characterized by high infiltration rate and great angiogenic capacity. The presence of an inflammatory microenvironment contributes to chemo/radioresistance, resulting in poor prognosis for patients. Recent data show that thiazolidinones have a wide range of pharmacological properties, including anti-inflammatory and antiglioma activities. Nanocapsules of biodegradable polymers become an alternative to cancer treatment since they provide targeted drug delivery and could overcome blood–brain barrier. Therefore, here we investigated the in vitro antiglioma activity and the potential in vivo toxicity of 2- (2-methoxyphenyl) -3- ((piperidin-1-yl) ethyl) thiazolidin-4-one-loaded polymeric nanocapsules ( 4L-N ). Nanocapsules were prepared and characterized in terms of particle size, polydispersity index, zeta potential, pH, molecule content and encapsulation efficiency. Treatment with 4L-N selectively decreased human U138MG and rat C6 cell lines viability and proliferation, being even more efficient than the free-form molecule ( 4L ). In addition, 4L-N did not promote toxicity to primary astrocytes. We further demonstrated that the treatment with sub-therapeutic dose of 4L-N did not alter weight, neither resulted in mortality, toxicity or peripheral damage to Wistar rats. Finally, 4L as well as 4L-N did not alter makers of oxidative damage, such as TBARS levels and total sulfhydryl content, and did not change antioxidant enzymes SOD and CAT activity in liver and brain of treated rats. Taken together, these data indicate that the nanoencapsulation of 4L has potentiated its antiglioma effect and does not cause in vivo toxicity. Graphical Abstract