Lipid-Core Nanocapsules Act as a Drug Shuttle Through the Blood Brain Barrier and Reduce Glioblastoma After Intravenous or Oral Administration

Autor(es)

Rodrigues, Stephen F. ^[1] ; Fiel, Luana A. ^[2] ; Shimada, Ana L. ^[1] ; Pereira, Natalia R. ^[1] ; Guterres, Silvia S. ^[2] ; Pohlmann, Adriana R. ^{[2, 3]} ; Farsky, Sandra H. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Lab Expt Toxicol, Dept Clin & Toxicol Anal, Sch Pharmaceut Sci, BR-05508900 Sao Paulo - Brazil

^[2] Univ Fed Rio Grande do Sul, Programa Posgrad Ciencias Farmaceut, Fac Farm, BR-90610000 Porto Alegre, RS - Brazil

^[3] Univ Fed Rio Grande do Sul, Dept Quim Organ, Inst Quim, BR-91501970 Porto Alegre, RS - Brazil

• Tipo de documento: Artigo Científico
• Fonte: JOURNAL OF BIOMEDICAL NANOTECHNOLOGY; v. 12, n. 5, p. 986-1000, MAY 2016.
• Citações Web of Science: 25

Resumo

Lipid-core nanocapsules (LNC) are formed by an organogel surrounded by poly(epsilon-caprolactone) and stabilized by polysorbate 80. LNCs increase the concentration of drugs in the brain after oral or intravenous administration. We proposed to determine whether the drug is released from the LNC to cross the blood brain barrier (BBB) or the drug-loaded LNCs can cross the BBB to release the drug. We synthesized a Rhodamine B-polymer conjugate to prepare a fluorescent-labeled LNC formulation, and intravital microscopy was used to determine the ability of the LNCs to cross the brain barrier using different administration routes in C57BI/6 mice. A glioblastoma model was used to determine the impact of the LNC as a shuttle for treatment. After pial vessel exposure, intense fluorescence was detected inside the vessels 10 min after intravenous or 20 min after intraperitoneal injections of fluorescent-labeled LNC. The fluorescence was observed in the perivascular tissue after 30 and 60 min, respectively. Increased tissue fluorescence was detected 240 min after oral administration. The integrity of the barrier was determined during the experiments. Normal leukocyte and platelet adhesion to the vessel wall indicated that Rhodamine 6-labeled LNC did not cause pial vessel alterations. After intravenous or oral administration, Rhodamine 6-labeled LNC-containing co-encapsulated indomethacin and indomethacin ethyl ester exhibited similar behavior in pial vessels, being more efficient in the treatment of mice with glioblastoma than indomethacin in solution. Therefore, we demonstrated that LNCs act as drug shuttles through the BBB, delivering drugs in brain tissue with high efficiency and reducing glioblastoma after intravenous or oral administration. (AU)

• Processo FAPESP: 11/19595-9 - Estudo da eficácia terapêutica de nanocápsulas de indometacina e éster etílico de indometacina: ensaios de microscopia intravital
• Beneficiário: Sandra Helena Poliselli Farsky
• Linha de fomento: Auxílio à Pesquisa - Regular
• Processo FAPESP: 11/02438-8 - Eficácia terapêutica de nanocápsulas de indometacina e éster etílico de indometacina na microcirculação cerebral de camundongos: estudos in vivo e ex vivo
• Beneficiário: Stephen Fernandes de Paula Rodrigues
• Linha de fomento: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 12/02994-0 - Estudo experimental da exposição ao PCB126 sobre a indução de Diabetes mellitus tipo II
• Beneficiário: Sandra Helena Poliselli Farsky
• Linha de fomento: Auxílio à Pesquisa - Regular
• Processo FAPESP: 14/05146-6 - Eficácia terapêutica de nanopartículas de ouro em glioblastoma multiforme ou encefalopatia séptica em camundongas
• Beneficiário: Stephen Fernandes de Paula Rodrigues
• Linha de fomento: Auxílio à Pesquisa - Apoio a Jovens Pesquisadores