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Nanocarriers for localized treatment and chemoprevention of breast tumors

Grant number: 18/13877-1
Support Opportunities:Research Grants - Young Investigators Grants - Phase 2
Duration: May 01, 2019 - April 30, 2025
Field of knowledge:Health Sciences - Pharmacy - Pharmaceutical Technology
Principal Investigator:Luciana Biagini Lopes
Grantee:Luciana Biagini Lopes
Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Associated researchers:Ana Paula Lepique ; João Agostinho Machado Neto ; Leticia Veras Costa Lotufo ; Soraia Katia Pereira Costa
Associated research grant:13/16617-7 - Nanostructured systems for topical delivery and co-localization of chemopreventive and chemoterapeutic agents in the skin and breast tissue, AP.JP
Associated grant(s):19/21910-1 - Multi-User Equipment approved in grant 208/13877-1: equipment for high performance liquid chromatography (HPLC), AP.EMU
Associated scholarship(s):23/13424-5 - Comparative evaluation of methodologies for studying the in vitro cytotoxicity of theranostic nanosystems in a 3D breast cancer culture model, BP.IC
22/12876-7 - Study of pectin-chitosan systems enriched with nanostructured lipid carriers for the delivery of nisin, simvastatin and adenosine aiming the treatment of skin ulcers, BP.PD
22/16767-8 - Low energy methods for the obtainment of nanocarriers for topical delivery of antioxidant peptides and proteins, BP.IC
+ associated scholarships 22/00997-4 - Nanostructured lipid carriers for co-encapsulation and sustained release of fenretinide and perillyl alcohol in the mammary tissue aiming at prevention of development and recurrences of Breast Cancer, BP.DD
21/12658-7 - Development of chitosan-hyaluronic acid polyelectrolyte nanoparticles for intraductal delivery, BP.IC
21/06755-0 - Evaluation of nanoemulsions for local-transdermal administration of fenretinide for breast cancer chemoprevention, BP.MS
19/26048-6 - Development and application of multifunctional nanocarriers for intraductal delivery of chemotherapy aiming at Breast Cancer treatment, BP.DR
20/04633-1 - Study of the influence of nanocarriers and drug combinations on cell viability and migration, BP.IC
19/03241-5 - Preparation and evaluation of oral nanocarriers of 5-fluorouracil and intestinal metabolics, BP.DR
20/01208-8 - Bioadhesive nanostructured systems for intraductal administration and localized treatment of Breast Cancer, BP.DD
18/14375-0 - Nanotechnology-based topical delivery systems for breast cancer chemoprevention, BP.PD - associated scholarships

Abstract

Considering the high incidence of breast tumors and the lack of strategies for local management of non-invasive cases, as well as effective, safe and well-accepted chemoprevention alternatives for high-risk population, we propose the development of nanotechnology-based strategies to fill this gap. To increase treatment efficacy, we propose to co-encapsulate combinations of cytotoxic, cicloxigenase-2 inhibitors and anti-proliferative agents, which may potentiate each other effects due to interference with multiple signaling pathways. We will develop nanocarriers for the intraductal, topical and subcutaneous routes, aiming local application to the breast tissue. Nanoemulsions, polyelectrolyte nanoparticles, nanodispersions and microemulsions will be developed, and their diameter, zeta potential, rheological, bioadhesive and swelling properties will be characterized. Subsequently, we will study the influence of composition on skin permeability, skin penetration and percutaneous delivery, irritation potential, formulation residence and drug delivery in the mammary tissue. The influence of nanoencapsulation and association of drugs on cytotoxicity and anti-proliferative effects, as well as selective effects of drugs and formulations against cancer cells will be assessed in 2D cultures and 3D multicellular spheroids. Results from these studies will enable selection of formulations for assessment of in vivo efficacy in models of breast cancer. (AU)

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Scientific publications (26)
(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)
APOLINARIO, ALEXSANDRA CONCEICAO; HAUSCHKE, LEON; NUNES, JESSICA RIBEIRO; LOPES, LUCIANA BIAGINI. Towards nanoformulations for skin delivery of poorly soluble API: What does indeed matter?. JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY, v. 60, . (18/14375-0, 18/13877-1)
APOLINARIO, ALEXSANDRA CONCEICAO; HAUSCHKE, LEON; NUNES, JESSICA RIBEIRO; LOPES, LUCIANA BIAGINI. Lipid nanovesicles for biomedical applications: `What is in a name'?. PROGRESS IN LIPID RESEARCH, v. 82, . (18/14375-0, 14/50928-2, 18/13877-1)
MOJEIKO, GABRIELA; PASSOS, JULIA SAPIENZA; APOLINARIO, ALEXSANDRA CONCEICAO; LOPES, LUCIANA BIAGINI. opical transdermal chemoprevention of breast cancer: where will nanomedical approaches deliver us. Nanomedicine, v. 16, n. 19, . (18/13877-1, 18/14375-0, 19/00196-9, 20/01208-8, 14/50928-2)
COSTA-FERNANDEZ, SANDRA; MATOS, JENYFFER K. R.; SCHEUNEMANN, GABY S.; SALATA, GIOVANNA C.; CHORILLI, MARLUS; WATANABE, IL-SEI; DE ARAUJO, GABRIEL L. B.; SANTOS, MARINILCE F.; ISHIDA, KELLY; LOPES, LUCIANA B.. Nanostructured lipid carriers containing chitosan or sodium alginate for co-encapsulation of antioxidants and an antimicrobial agent for potential application in wound healing. International Journal of Biological Macromolecules, v. 183, p. 668-680, . (14/50928-2, 19/26048-6, 13/16617-7, 15/07993-0, 17/19374-9, 18/13877-1)
SANTOS, ROGERIO A.; RAE, MARIANA; DARTORA, VANESSA F. M. C.; MATOS, JENYFFER K. R.; CAMARINI, ROSANA; LOPES, LUCIANA B.. Bioresponsive nanostructured systems for sustained naltrexone release and treatment of alcohol use disorder: Development and biological evaluation. International Journal of Pharmaceutics, v. 585, . (17/04174-4, 18/05038-0, 18/13877-1, 13/16617-7, 18/18813-1, 15/02397-0)
BARRETO, THAYNA LOPES; ROSSATO, LUANA; DUARTE DE FREITAS, ALINE LUIZA; MEIS, JACQUES F.; LOPES, LUCIANA BIAGINI; COLOMBO, ARNALDO LOPES; ISHIDA, KELLY. Miltefosine as an alternative strategy in the treatment of the emerging fungus Candida auris. INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS, v. 56, n. 2, . (17/19374-9, 18/13877-1, 18/03708-8, 17/15226-5, 17/02203-7, 17/19095-2)
APOLINARIO, ALEXSANDRA CONCEICAO; SALATA, GIOVANNA CASSONE; DE SOUZA, MARCELO MEDINA; CHORILLI, MARLUS; LOPES, LUCIANA BIAGINI. Rethinking Breast Cancer Chemoprevention: Technological Advantages and Enhanced Performance of a Nanoethosomal-Based Hydrogel for Topical Administration of Fenretinide. AAPS PHARMSCITECH, v. 23, n. 4, p. 14-pg., . (18/13877-1, 14/50928-2, 20/13139-0, 18/14375-0)
GIACONE, V, DANIELA; DARTORA, VANESSA F. M. C.; DE MATOS, JENYFFER K. R.; PASSOS, JULIA S.; MIRANDA, DANIEL A. G.; DE OLIVEIRA, ERICA A.; SILVEIRA, EDILBERTO R.; COSTA-LOTUFO, V, LETICIA; MARIA-ENGLER, SILVYA S.; LOPES, LUCIANA B.. Effect of nanoemulsion modification with chitosan and sodium alginate on the topical delivery and efficacy of the cytotoxic agent piplartine in 2D and 3D skin cancer models. International Journal of Biological Macromolecules, v. 165, n. A, p. 1055-1065, . (17/07856-9, 15/17177-6, 16/16554-3, 17/04174-4, 20/01208-8, 18/18813-1, 18/13877-1)
MIGUEL, RODRIGO DOS A.; HIRATA, AMANDA S.; JIMENEZ, PAULA C.; LOPES, LUCIANA B.; COSTA-LOTUFO, LETICIA V.. Beyond Formulation: Contributions of Nanotechnology for Translation of Anticancer Natural Products into New Drugs. PHARMACEUTICS, v. 14, n. 8, p. 28-pg., . (20/09270-4, 18/13877-1, 20/06613-8, 15/17177-6)
MORETTI, EDUARDO H.; RODRIGUES, ABNER C.; MARQUES, BRUNO V.; TOTOLA, LEONARDO T.; FERREIRA, CAROLINE B.; BRITO, CAMILA F.; MATOS, CAROLINE M.; DA SILVA, FILIPE A.; SANTOS, ROBSON A. S.; LOPES, LUCIANA B.; et al. Autoregulation of blood flow drives early hypotension in a rat model of systemic inflammation induced by bacterial lipopolysaccharide. PNAS NEXUS, v. 2, n. 2, p. 13-pg., . (18/13877-1, 20/00631-4, 18/03418-0, 20/09399-7, 15/23376-1, 18/21934-5)
SPADARI, CRISTINA DE CASTRO; WIRTH, FERNANDA; LOPES, LUCIANA BIAGINI; ISHIDA, KELLY. New Approaches for Cryptococcosis Treatment. MICROORGANISMS, v. 8, n. 4, . (17/19374-9, 18/12149-2, 18/13877-1)
FUKUMORI, CLAUDIO; BRANCO, PAOLA CRISTINA; BARRETO, THAYNA; ISHIDA, KELLY; LOPES, LUCIANA B.. Development and cytotoxicity evaluation of multiple nanoemulsions for oral co-delivery of 5-fluorouracil and short chain triglycerides for colorectal cancer. European Journal of Pharmaceutical Sciences, v. 187, p. 15-pg., . (18/13877-1, 14/50928-2, 19/03241-5)
DONADON, LARISSA GABRIELLA FUSCO; SALATA, GIOVANNA CASSONE; GONCALVES, THALITA PEDRALINO; MATOS, LISA DE CARVALHO; EVANGELISTA, MARIA CLARA PAIVA; DA SILVA, NICOLE SAMPAIO; MARTINS, TEREZA SILVA; MACHADO-NETO, JOAO AGOSTINHO; LOPES, LUCIANA BIAGINI; GARCIA, MARIA TERESA JUNQUEIRA. Monoolein-based nanodispersions for cutaneous co-delivery of methylene blue and metformin: Thermal and structural characterization and effects on the cutaneous barrier, skin penetration and cytotoxicity. International Journal of Pharmaceutics, v. 633, p. 18-pg., . (17/18239-0, 18/13877-1, 17/17844-8, 19/08582-5, 19/26048-6)
APOLINARIO, ALEXSANDRA CONCEICAO; HAUSCHKE, LEON; NUNES, JESSICA RIBEIRO; LOURENCO, FELIPE REBELLO; LOPES, LUCIANA BIAGINI. Design of multifunctional ethosomes for topical fenretinide delivery and breast cancer chemoprevention. COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS, v. 623, . (14/50928-2, 18/14375-0, 18/13877-1)
ALEXSANDRA CONCEIÇÃO APOLINÁRIO; GIOVANNA CASSONE SALATA; ARTHUR F. R. BIANCO; CLAUDIO FUKUMORI; LUCIANA BIAGINI LOPES. ABRINDO A CAIXA DE PANDORA DOS NANOMEDICAMENTOS: HÁ REALMENTE MUITO MAIS ‘ESPAÇO LÁ EMBAIXO’. Química Nova, v. 43, n. 2, p. 212-225, . (14/50928-2, 17/23213-0, 18/13877-1, 18/14375-0)
MOJEIKO, GABRIELA; APOLINARIO, ALEXSANDRA CONCEICA; SALATA, GIOVANNA CASSONE; CHORILLI, MARLUS; LOPES, LUCIANA B.. Optimization of nanoemulsified systems containing lamellar phases for co-delivery of celecoxib and endoxifen to the skin aiming for breast cancer chemoprevention and treatment. COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS, v. 646, p. 14-pg., . (19/26048-6, 18/14375-0, 19/00196-9, 18/13877-1, 14/50928-2)
PASSOS, JULIA SAPIENZA; DE MARTINO, LUIZA CAPELLO; CARVALHO DARTORA, VANESSA FRANCO; DE ARAUJO, GABRIEL L. B.; ISHIDA, KELLY; LOPES, LUCIANA B.. Development, skin targeting and antifungal efficacy of topical lipid itraconazole. European Journal of Pharmaceutical Sciences, v. 149, . (17/04174-4, 14/50928-2, 17/19374-9, 15/07993-0, 18/13877-1, 13/16617-7)
MENDES DA SILVA DE BASTIANI, FERNANDA WALT; SPADARI, CRISTINA DE CASTRO; ROCHA DE MATOS, JENYFFER KELLY; SALATA, GIOVANNA CASSONE; LOPES, LUCIANA BIAGINI; ISHIDA, KELLY. Nanocarriers Provide Sustained Antifungal Activity for Amphotericin B and Miltefosine in the Topical Treatment of Murine Vaginal Candidiasis. FRONTIERS IN MICROBIOLOGY, v. 10, . (17/19374-9, 15/07993-0, 18/13877-1)
SALATA, GIOVANNA CASSONE; MALAGO, ISABELLA D.; CARVALHO DARTORA, VANESSA F. M.; MARCAL PESSOA, ANA FLAVIA; DE ABREU FANTINI, MARCIA CARVALHO; COSTA, SORAIA K. P.; MACHADO-NETO, JOAO AGOSTINHO; LOPES, LUCIANA B.. Microemulsion for Prolonged Release of Fenretinide in the Mammary Tissue and Prevention of Breast Cancer Development. MOLECULAR PHARMACEUTICS, v. 18, n. 9, p. 3401-3417, . (14/50928-2, 19/23864-7, 16/06146-5, 17/23213-0, 18/13877-1)
SALATA, GIOVANNA CASSONE; LOPES, LUCIANA B.. Phosphatidylcholine-Based Nanoemulsions for Paclitaxel and a P-Glycoprotein Inhibitor Delivery and Breast Cancer Intraductal Treatment. PHARMACEUTICALS, v. 15, n. 9, p. 23-pg., . (18/13877-1, 14/50928-2)
CARVALHO, VANESSA F. M.; SALATA, GIOVANNA C.; DE MATOS, JENYFFER K. R.; COSTA-FERNANDEZ, SANDRA; CHORILLI, MARLUS; STEINER, ALEXANDRE A.; DE ARAUJO, GABRIEL L. B.; SILVEIRA, EDILBERTO R.; COSTA-LOTUFO, V, LETICIA; LOPES, LUCIANA B.. Optimization of composition and obtainment parameters of biocompatible nanoemulsions intended for intraductal administration of piplartine (piperlongumine) and mammary tissue targeting. International Journal of Pharmaceutics, v. 567, . (17/23213-0, 13/16617-7, 17/04174-4, 18/03418-0, 18/18813-1, 18/13877-1)
BARRETO, THAYNA L.; LOPES, LUCIANA B.; MELO, ANALY S. A.; ISHIDA, KELLY. In vivo synergism of free miltefosine or in alginate-based nanocarrier combined with voriconazole on aspergillosis. FUTURE MICROBIOLOGY, v. 16, n. 15, . (17/19374-9, 15/07993-0, 18/03708-8, 18/13877-1)
APOLINARIO, ALEXSANDRA CONCEICAO; HIRATA, AMANDA SOARES; ANJOS MIGUEL, RODRIGO DOS; COSTA-LOTUFO, LETICIA VERAS; PESSOA, ADALBERTO; LA CLAIR, JAMES J.; FENICAL, WILLIAM; LOPES, LUCIANA BIAGINI. Exploring the benefits of nanotechnology for cancer drugs in different stages of the drug development pipeline. Nanomedicine, v. 15, n. 26, p. 4-pg., . (18/13877-1, 15/17177-6, 18/07661-6, 18/14375-0)
SALATA, GIOVANNA C.; MALAGO, ISABELLA D.; LOPES, LUCIANA B.. A Lipid-Based In Situ-Forming Hexagonal Phase for Prolonged Retention and Drug Release in the Breast Tissue. AAPS PHARMSCITECH, v. 23, n. 7, p. 14-pg., . (14/50928-2, 18/13877-1, 19/23864-7)
PASSOS, JULIA SAPIENZA; DARTORA, VANESSA F. M. C.; SALATA, GIOVANNA CASSONE; MALAGO, ISABELLA DRASZESSKI; LOPES, LUCIANA B.. Contributions of nanotechnology to the intraductal drug delivery for local treatment and prevention of breast cancer. International Journal of Pharmaceutics, v. 635, p. 15-pg., . (18/13877-1, 17/04174-4, 20/01208-8, 14/50928-2, 19/26048-6)
GIACONE, DANIELA, V; DARTORA, VANESSA F. M. C.; DE MATOS, JENYFFER K. R.; PASSOS, JULIA S.; MIRANDA, DANIEL A. G.; DE OLIVEIRA, ERICA A.; SILVEIRA, EDILBERTO R.; COSTA-LOTUFO, LETICIA, V; MARIA-ENGLER, SILVYA S.; LOPES, LUCIANA B.. Effect of nanoemulsion modification with chitosan and sodium alginate on the topical delivery and efficacy of the cytotoxic agent piplartine in 2D and 3D skin cancer models. International Journal of Biological Macromolecules, v. 165, p. 11-pg., . (18/13877-1, 18/18813-1, 17/07856-9, 17/04174-4, 20/01208-8, 15/17177-6, 16/16554-3)

Please report errors in scientific publications list using this form.
Filed patent(s) as a result of this research project

NANOEMULSÃO MÚLTIPLA, SEU PROCESSO DE OBTENÇÃO E USO DA MESMA BR1020200181998 - Universidade de São Paulo (USP) . LUCIANA BIAGINI LOPES / CLAUDIO FUKUMORI / PAOLA CRISTINA BRANCO - September 2020, 04

NANOFORMULAÇÕES COMPREENDENDO FENRETINIDA, PROCESSO DE OBTENÇÃO DAS MESMAS E USO DESTAS NA PREPARAÇÃO DE UM MEDICAMENTO PARA A QUIMIOPREVENÇÃO DO CÂNCER DE MAMA E/OU NA PREVENÇÃO E/OU TRATAMENTO DO CÂNCER DE PELE E DE MUCOSAS BR1020210024933 - Universidade de São Paulo (USP) . LUCIANA BIAGINI LOPES, ALEXSANDRA CONCEIÇÃO APOLINÁRIO, JESSICA RIBEIRO NUNES - February 2021, 09

NANOFORMULAÇÃO EM GEL POLIMÉRICO ETOSSOMAL E SEU USO NA PREPARAÇÃO DE UM MEDICAMENTO PARA A QUIMIOPREVENÇÃO DO CÂNCER DE MAMA E NA PREVENÇÃO E/OU TRATAMENTO DO CÂNCER DE PELE E CERVICAL BR1020210221771 - Universidade de São Paulo (USP) . LUCIANA BIAGINI LOPES, GIOVANNA CASSONE SALATA, ALEXSANDRA CONCEIÇÃO APOLINÁRIO, GABRIELA MOJEIKO - November 2021, 04

PROCESSO DE OBTENÇÃO DE SISTEMAS NANOESTRUTURADOS, CRISTAIS LÍQUIDOS DO TIPO LAMELAR DE FORMA ESTÁVEL, USO DOS REFERIDOS CRISTAIS LÍQUIDOS, PROCESSO DE OBTENÇÃO DE NANOPARTÍCULAS DE ALBUMINA, AS REFERIDAS NANOPARTÍCULAS DE ALBUMINA E USOS DAS NANOPARTÍCULAS DE ALBUMINA BR1020210222808 - Universidade de São Paulo (USP) . LUCIANA BIAGINI LOPES, ALEXSANDRA CONCEIÇÃO APOLINÁRIO, RODRIGO DOS ANJOS MIGUEL, KELLY ISHIDA, VINÍCIUS MORAIS BARROSO, AMANDA SOARES HIRATA, LETICIA VERAS COSTA LOTUFO - November 2021, 05