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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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Author(s):
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]
Total Authors: 7
Affiliation:
[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
Total Affiliations: 3
Document type: Journal article
Source: JOURNAL OF BIOMEDICAL NANOTECHNOLOGY; v. 12, n. 5, p. 986-1000, MAY 2016.
Web of Science Citations: 25
Abstract

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)

FAPESP's process: 12/02994-0 - Experimental study of PCB126 exposure on induction type II Diabetes mellitus
Grantee:Sandra Helena Poliselli Farsky
Support Opportunities: Regular Research Grants
FAPESP's process: 14/05146-6 - Therapeutical efficacy of gold nanoparticles to glioblastoma multiform or septic encephalopathy in mice
Grantee:Stephen Fernandes de Paula Rodrigues
Support Opportunities: Research Grants - Young Investigators Grants
FAPESP's process: 11/02438-8 - THERAPEUTIC EFFICACY OF INDOMETHACIN AND INDOMETHACIN ETHYL ESTER NANOCAPSULES IN THE CEREBRAL MICROCIRCULATION OF MICE: IN VIVO AND EX VIVO STUDIES
Grantee:Stephen Fernandes de Paula Rodrigues
Support Opportunities: Scholarships in Brazil - Post-Doctorate
FAPESP's process: 11/19595-9 - Study of therapy effectiveness of indomethacin and ethyl ester indomethacin nanocapsules: intravital microscopy assays
Grantee:Sandra Helena Poliselli Farsky
Support Opportunities: Regular Research Grants