Potential evaluation of nanostructured lipid carriers functionalized with bevacizumab for delivery of docetaxel in the treatment of glioblastoma

• Grant number: 18/18488-3
• Support Opportunities: Scholarships in Brazil - Master
• Start date: August 01, 2019
• End date: February 28, 2021
• Field of knowledge: Health Sciences - Pharmacy - Pharmaceutical Technology
• Principal Investigator: Marlus Chorilli
• Grantee: Leonardo Delello Di Filippo
• Host Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil
• Associated scholarship(s): 19/26225-5 - In vitro anti-tumor efficacy of bevacizumab-functionalized nanostructured lipid carrier containing docetaxel for the treatment of glioblastoma multiforme, BE.EP.MS

Abstract

Glioblastoma (GBM) is the most common primary malignant cancer of the central nervous system, responsible for about 4% of the deaths associated with tumors, characterizing itself as one of the most fatal cancers. Chemotherapy is widely used in treatment and docetaxel (DTX), Taxotere®, is a chemotherapeutic drug that has demonstrated efficacy in GBM treatment, inhibiting cell proliferation by mitotic block, by preventing the depolymerization of microtubules , making them unstable and nonfunctional, so that the cell is not able to divide and dies by apoptosis. However, Taxotere® has side effects associated with toxicity as well as limited bioavailability, which limits its clinical use. A very attractive approach is the encapsulation in nanostructured lipid carriers (CLN), functionalized with specific ligands of receptors present on the surfaces of tumor cells, in order to overcome the blood-brain barrier (BBB) and to make the drug available more efficiently. CLNs are useful in chemotherapy because they improve the bioavailability of the drugs, being able to selectively deliver them to the cancer cells, reducing the systemic toxicity and increasing the effectiveness of the treatment. The current work aims at evaluating the potential of nanostructured lipid carriers functionalized with bevacizumab for the delivery of docetaxel in the treatment of glioblastoma. The CLNs will be obtained by the fusion-emulsification technique. The CLNs will be functionalized by the thiolation reaction of bevacizumab. The CLN will be characterized by physico-chemical techniques regarding its size, morphology, polydispersity index, zeta potential, encapsulation efficiency and functionalization efficiency. The integrity of bevacizumab in the functionalized CLNs will be verified by SDS-PAGE assays and circular dichroism. Release assays will be performed for conventional CLNs and functionalized with bevacizumab. Finally, in vitro biological assays will be performed to evaluate the cytotoxicity of the formulation in lineages that overexpress or not VEGF. Therefore, it is expected to obtain an innovative, target-specific CLN that allows targeted delivery of docetaxel in sufficient amounts as an alternative to the pharmacological treatment of GBM. (AU)

Scientific publications

(10)

(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)

DE ARAUJO, JENNIFER THAYANNE CAVALCANTE; DUARTE, JONATAS LOBATO; DI FILIPPO, LEONARDO DELELLO; ARAUJO, VICTOR HUGO SOUSA; CARVALHO, GABRIELA CORREA; CHORILLI, MARLUS. Nanosystem functionalization strategies for prostate cancer treatment: a review. Journal of Drug Targeting, FEB 2021. (18/18488-3)

DI FILIPPO, LEONARDO DELELLO; DUARTE, JONATAS LOBATO; AZAMBUJA, JULIANA HOFSTATTER; MANCUSO, RUBIA ISLER; LUIZ, MARCELA TAVARES; SOUSA ARAUJO, VICTOR HUGO; FIGUEIREDO, INGRID DELBONE; BARRETTO-DE-SOUZA, LUCAS; SABIO, RAFAEL MIGUEL; SASSO-CERRI, ESTELA; et al. Glioblastoma multiforme targeted delivery of docetaxel using bevacizumab-modified nanostructured lipid carriers impair in vitro cell growth and in vivo tumor progression. International Journal of Pharmaceutics, v. 618, p. 12-pg., 2022-04-25. (19/25125-7, 18/18488-3)

DI FILIPPO, LEONARDO DELELLO; DUARTE, JONATAS LOBATO; LUIZ, MARCELA TAVARES; CAVALCANTE DE ARAUJO, JENNIFER THAYANNE; CHORILLI, MARLUS. Drug Delivery Nanosystems in Glioblastoma Multiforme Treatment: Current State of the Art. Current Neuropharmacology, v. 19, n. 6, p. 787-812, 2021. (18/18488-3)

DUARTE, JONATAS LOBATO; DI FILIPPO, LEONARDO DELELLO; SOUSA ARAUJO, VICTOR HUGO; DE FARIA MOTA OLIVEIRA, ANNA ELIZA MACIEL; CAVALCANTE DE ARAUJO, JENNIFER THAYANNE; DA ROCHA SILVA, FLAVIA BENINI; PINTO, MARA CRISTINA; CHORILLI, MARLUS. Nanotechnology as a tool for detection and treatment of arbovirus infections. Acta Tropica, v. 216, APR 2021. (18/18488-3, 19/25125-7)

DI FILIPPO, LEONARDO DELELLO; DOS SANTOS, KAREN CRISTINA; HANCK-SILVA, GILMAR; DE LIMA, FELIPE TITA; GREMIAO, MARIA PALMIRA DAFLON; CHORILLI, MARLUS. A Critical Review of Biological Properties, Delivery Systems and Analytical/Bioanalytical Methods for Determination of Bevacizumab. CRITICAL REVIEWS IN ANALYTICAL CHEMISTRY, APR 2020. (18/23430-4, 18/18488-3)

DI FILIPPO, LEONARDO DELELLO; DOS SANTOS, KAREN CRISTINA; HANCK-SILVA, GILMAR; DE LIMA, FELIPE TITA; GREMIAO, MARIA PALMIRA DAFLON; CHORILLI, MARLUS. A Critical Review of Biological Properties, Delivery Systems and Analytical/Bioanalytical Methods for Determination of Bevacizumab. CRITICAL REVIEWS IN ANALYTICAL CHEMISTRY, v. 51, n. 5, p. 445-453, JUL 4 2021. (18/18488-3, 18/23430-4)

DE ARAUJO, JENNIFER THAYANNE CAVALCANTE; DUARTE, JONATAS LOBATO; DI FILIPPO, LEONARDO DELELLO; ARAUJO, VICTOR HUGO SOUSA; CARVALHO, GABRIELA CORREA; CHORILLI, MARLUS. Nanosystem functionalization strategies for prostate cancer treatment: a review. Journal of Drug Targeting, v. 29, n. 8, p. 808-821, SEP 14 2021. (18/18488-3)

POLLI SILVESTRE, AMANDA LETICIA; DI FILIPPO, LEONARDO DELELLO; BESEGATO, JOAO FELIPE; DE ANNUNZIO, SARAH RAQUEL; FURQUIM DE CAMARGO, BRUNA ALMEIDA; GOBBO DE MELO, PRISCILA BORGES; DE SOUZA RASTELLI, ALESSANDRA NARA; FONTANA, CARLA RAQUEL; CHORILLI, MARLUS. Current applications of drug delivery nanosystems associated with antimicrobial photodynamic therapy for oral infections. International Journal of Pharmaceutics, v. 592, JAN 5 2021. (18/23015-7, 18/23096-7, 18/18488-3, 18/09088-1)

DUARTE, JONATAS L.; TAIRA, THAIS C.; DI FILIPPO, LEONARDO DELELLO; FONSECA-SANTOS, BRUNO; PINTO, MARA CRISTINA; CHORILLI, MARLUS. Novel bioadhesive polycarbophil-based liquid crystal systems containing Melaleuca alternifolia oil as potential repellents against Aedes aegypti. JOURNAL OF MOLECULAR LIQUIDS, v. 314, SEP 15 2020. (18/18488-3, 17/23357-2)

DE ARAUJO, JENNIFER THAYANNE CAVALCANTE; TAVARES JUNIOR, ALBERTO GOMES; DI FILIPPO, LEONARDO DELELLO; DUARTE, JONATAS LOBATO; RIBEIRO, TAIS DE CASSIA; CHORILLI, MARLUS. Overview of chitosan-based nanosystems for prostate cancer therapy. EUROPEAN POLYMER JOURNAL, v. 160, NOV 5 2021. (19/19228-8, 19/25125-7, 18/18488-3, 20/06212-3)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

FILIPPO, Leonardo Delello Di. Evaluation of the potential of nanostructured lipid carriers functionalized with bevacizumab for delivery of docetaxel in the treatment of glioblastoma multiforme. 2021. Master's Dissertation - Universidade Estadual Paulista (Unesp). Faculdade de Ciências Farmacêuticas. Araraquara Araraquara.