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Solid lipid nanoparticles for incorporation of trans-resveratrol in the topical treatment of melanoma: in vitro and in vivo evaluation and the elucidation of the mechanism of uptake cellular

Grant number: 13/21500-1
Support Opportunities:Scholarships in Brazil - Doctorate
Effective date (Start): June 01, 2014
Effective date (End): June 30, 2017
Field of knowledge:Health Sciences - Pharmacy - Pharmaceutical Technology
Acordo de Cooperação: Coordination of Improvement of Higher Education Personnel (CAPES)
Principal Investigator:Marlus Chorilli
Grantee:Roberta Balansin Rigon
Host Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil
Associated scholarship(s):16/02195-1 - Characterization of the penetrability of flexible and rigid nanoparticles into reconstructed human skin, BE.EP.DR


The incidence of skin cancers has increased, and melanoma (MEL) is the most serious type. The treatment choice involves the administration of chemotherapy, which may have cytotoxic action also on healthy cells, affecting quality and survival of patients. Trans-resveratrol (RES) has shown excellent results in the prevention and treatment of MEL. However, this substance has low bioavailability and rapid metabolism in vivo. Thus, its topical administration may be convenient to locate the drug on their site of action. Nanostructured lipid systems such as solid lipid nanoparticles (SLN) are gaining notoriety as carriers for topical administration of drugs, in virtue of their interaction with the stratum corneum and other layers of the skin, and the ability of the drug with arrangement protective effect and sustainer of release. The effects caused by NLS vary according to their ability to reach the target tissue and enter the cell. The detailed characterization of the interactions that occur between these systems and biological systems is of crucial importance for the formulation development of high therapeutic efficiency. Data obtained by our research group showed that SLN consisting of stearic acid (SA) or polyoxyethylene (40) stearate (EP40) as a lipid phase and poloxamer 407 (P407) plus soy phosphatidylcholine (FS) as surfactants were shown to be nontoxic in cell models of human keratinocytes (HaCat) and enabled the controlled release and penetration of RES in the epidermis. The incorporation of cationic lipids such as glyceryl behenate (BH) in SLN may facilitate targeting to tumor cells, which have high negative charge because the exposure of phosphatidylserine (FS) on the surface of cell membranes. In this context, the present study has as objective the topical administration of SLN, composed of AE or EP40, P407/FS and water, with cationic lipid BG, for placement of RES in the treatment of MEL with evaluation their activity and efficiency in vitro / in vivo, as well as the research of the mechanisms of uptake cellular of these delivery systems. (AU)

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Scientific publications (4)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
RIGON, ROBERTA B.; FACHINETTI, NAIARA; SEVERINO, PATRICIA; SANTANA, MARIA H. A.; CHORILLI, MARLUS. Skin Delivery and in Vitro Biological Evaluation of Trans-Resveratrol-Loaded Solid Lipid Nanoparticles for Skin Disorder Therapies. Molecules, v. 21, n. 1, . (12/19568-4, 11/16888-5, 13/21500-1)
FONSECA-SANTOS, BRUNO; SILVA, PATRICIA BENTO; RIGON, ROBERTA BALASIN; SATO, MARIANA RILLO; CHORILLI, MARIUS. Formulating SLN and NLC as Innovative Drug Delivery Systems for Non-Invasive Routes of Drug Administration. Current Medicinal Chemistry, v. 27, n. 22, p. 3623-3656, . (15/05394-2, 13/09265-7, 14/24180-0, 13/21500-1, 16/11198-4)
FACHINETTI, NAIARA; RIGON, ROBERTA BALANSIN; ELOY, JOSIMAR O.; SATO, MARIANA RILLO; DOS SANTOS, KAREN CRISTINA; CHORILLI, MARLUS. Comparative Study of Glyceryl Behenate or Polyoxyethylene 40 Stearate-Based Lipid Carriers for Trans-Resveratrol Delivery: Development, Characterization and Evaluation of the In Vitro Tyrosinase Inhibition. AAPS PHARMSCITECH, v. 19, n. 3, p. 1401-1409, . (13/21500-1, 11/19018-1, 12/19568-4, 11/16888-5)
RIGON, ROBERTA BALANSIN; GONCALEZ, MAIRA LIMA; SEVERINO, PATRICIA; ALVES, DANILO ANTONINI; SANTANA, MARIA H. A.; SOUTO, ELIANA B.; CHORILLI, MARIUS. Solid lipid nanoparticles optimized by 2(2) factorial design for skin administration: Cytotoxicity in NIH3T3 fibroblasts. COLLOIDS AND SURFACES B-BIOINTERFACES, v. 171, p. 501-505, . (13/21500-1, 12/19568-4, 11/16888-5)
Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
RIGON, Roberta Balansin. Solid lipid nanoparticles for incorporation of trans-resveratrol in the topical treatment of melanoma: in vitro and in vivo evaluation and the elucidation of the mechanism of uptake cellular. 2017. Doctoral Thesis - Universidade Estadual Paulista (Unesp). Faculdade de Ciências Farmacêuticas. Araraquara Araraquara.

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