title: Resveratrol-loaded lipid-core nanocapsules treatment reduces in vitro and in vivo glioma growth.
abstract: The development of novel therapeutic strategies to treat gliomas remains critical as a result of the poor prognoses, inef-. ficient therapies and recurrence associated with these tumors. In this context, biodegradable nanoparticles are emerging as efficient drug delivery systems for the treatment of difficult-to-treat diseases such as brain tumors. In the current study, we evaluated the antiglioma effect of trans-resveratrol-loaded lipid-core nanocapsules (RSV-LNC) based on in vitro (C6 glioma cell line) and in vivo (brain-implanted C6 cells) models of the disease. In vitro, RSV-LNC decreased the viability of C6 glioma cells to a higher extent than resveratrol in solution. Interestingly, RSV-LNC treatment was not cytotoxic to hippocampal organotypic cultures, a model of healthy neural cells, suggesting selectivity for cancer cells. RSV-LNC induced losses in glioma cell viability through induction of apoptotic cell death, as assessed by Annexin-FITC/PI assay, which was preceded by an early arrest in the S and G1 phases of the cell cycle. In brain-implanted C6 tumors, treatment with RSV-LNC (5 mg/kg/day, i.p.) for 10 days promoted a marked decrease in tumor size and also reduced the incidence of some malignant tumor-associated characteristics, such as intratumoral hemorrhaging, intratumoral edema and pseudopalisading, compared to resveratrol in solution. Taken together, the results presented herein suggest that nanoencapsulation of resveratrol improves its antiglioma activity, thus providing a provocative foundation for testing the clinical usefulness of nanoformulations of this natural compound as a new chemotherapeutic strategy for the treatment of gliomas.
authors.affiliation: Departamento de Bioquímica, Institute de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, 90035-003, Brasil.
authors.forename: Fabrício
authors.initials: F
authors.lastname: Figueiró
authors.forename: Andressa
authors.initials: A
authors.lastname: Bernardi
authors.forename: Rudimar L
authors.initials: RL
authors.lastname: Frozza
authors.forename: Thatiana
authors.initials: T
authors.lastname: Terroso
authors.forename: Alfeu
authors.initials: A
authors.lastname: Zanotto-Filho
authors.forename: Elisa H F
authors.initials: EH
authors.lastname: Jandrey
authors.forename: José Claudio F
authors.initials: JC
authors.lastname: Moreira
authors.forename: Christianne G
authors.initials: CG
authors.lastname: Salbego
authors.forename: Maria I
authors.initials: MI
authors.lastname: Edelweiss
authors.forename: Adriana R
authors.initials: AR
authors.lastname: Pohlmann
authors.forename: Sílvia S
authors.initials: SS
authors.lastname: Guterres
authors.forename: Ana Maria O
authors.initials: AM
authors.lastname: Battastini
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D055598:Chemical Phenomena; D002626:Chemistry, Pharmaceutical; D004195:Disease Models, Animal; D016193:G1 Phase / Q000187:drug effects; D005910:Glioma / Q000188:drug therapy* / Q000473:pathology*; D006624:Hippocampus / Q000187:drug effects; D006801:Humans; D008055:Lipids / Q000737:chemistry*; D008297:Male; D053769:Nanocapsules / Q000737:chemistry*; D009368:Neoplasm Transplantation; D051381:Rats; D017208:Rats, Wistar; D000077185:Resveratrol; D016196:S Phase / Q000187:drug effects; D012996:Solutions; D013267:Stilbenes / Q000494:pharmacology / Q000627:therapeutic use*; D047368:Tumor Burden / Q000187:drug effects
chemical_list: D008055:Lipids; D053769:Nanocapsules; D012996:Solutions; D013267:Stilbenes; D000077185:Resveratrol