Nanostructured systems for topical delivery and co-localization of chemopreventive and chemoterapeutic agents in the skin and breast tissue

• Grant number: 13/16617-7
• Support type: Research Grants - Young Investigators Grants
• Duration: September 01, 2014 - August 31, 2019
• Field of knowledge: Health Sciences - Pharmacy - Pharmaceutical Technology
• Principal researcher: Luciana Biagini Lopes
• Grantee: Luciana Biagini Lopes
• Home Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Assoc. researchers: Norberto Peporine Lopes ; Silvya Stuchi Maria-Engler
• Associated grant(s): 18/13877-1 - Nanocarriers for localized treatment and chemoprevention of breast tumors, AP.JP2
• Associated scholarship(s): 19/00196-9 - Topical delivery of endoxifene and celecoxib using nanogels as a new alternative for the chemoprevention of breast tumors, BP.MS; 19/02143-0 - Lipid nanoparticles for sustained liberation of fenretinide and chemoprevention of breast cancer, BP.IC; 18/14375-0 - Nanotechnology-based topical delivery systems for breast cancer chemoprevention, BP.PD; + associated scholarships 18/18813-1 - Bioresponsive gels containing nanoparticles for exudate control and co-delivery of propranolol and adenosine for wound healing applications, BP.IC; 17/23213-0 - Biorresponsive systems for sustained drug release and breast cancer chemoprevention, BP.MS; 17/04174-4 - Development and evaluation of cationic bioadhesive nanocarriers as a platform to localize piplartine in the breast for tumor treatment, BP.DR; 17/07856-9 - Cationic nanoemulsions for piplartine cutaneous delivery and treatment of skin tumors, BP.IC; 16/23590-6 - Assessment of irritative potential, citotoxicity and retention of nanocarriers in mammary tissue aiming the breast cancer localized treatment, BP.IC; 16/04913-9 - Evaluation of cationic microemulsions as systems capable of increasing cutaneous retention and cytotoxicity of drugs, BP.IC; 15/23976-9 - Development, characterization and evaluation of microemulsions for paclitaxel and ceramide C6 topical delivery, BP.IC - associated scholarships

Abstract

Considering the high incidence of skin and breast tumors and the unavailability of strategies to localize drugs in these tissues while avoiding systemic exposure and side effects, we propose the development of cationic nanocarriers for topical delivery of chemopreventive and chemotherapeutic agents. Because tumor development and progression are multifactorial, the co-incorporation of compounds capable of interfering with multiple signaling cascades may potentiate each other effects' and improve the efficacy of the treatment. Based on these facts, we propose to combine agents that exhibit anti-proliferative, cytotoxic and estrogen receptor-modulating activity in cationic microemulsions. Cationic amphiphilic peptides that are able to penetrate across biological barriers will be added to the system to impart the positive charge and facilitate the translocation of active compounds across biological barriers. The internal structure, diameter, zeta potential and rheological properties of selected nanocarriers will be assessed. Subsequently, we will study whether and how formulation composition affects skin permeability, P-glycoprotein-mediated transport and skin penetration and distribution of the drugs. Formulations promoting co-localization of specific combinations of drugs will be selected for evaluation of cytotoxic effects in tumor cells in culture, skin equivalents of cancer and animal models of breast cancer. (AU)

Scientific publications

(15)

(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)

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, JUL 30 2020. Web of Science Citations: 0.

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, JUN 15 2020. Web of Science Citations: 0.

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, AUG 15 2019. Web of Science Citations: 2.

MOJEIKO, GABRIELA; DE BRITO, MOACIR; SALATA, GIOVANNA C.; LOPES, LUCIANA B. Combination of microneedles and microemulsions to increase celecoxib topical delivery for potential application in chemoprevention of breast cancer. International Journal of Pharmaceutics, v. 560, p. 365-376, APR 5 2019. Web of Science Citations: 3.

CARVALHO, VANESSA F. M.; GIACONE, DANIELA V.; COSTA-LOTUFO, LETICIA V.; SILVEIRA, EDILBERTO ROCHA; LOPES, LUCIANA B. Development of a method for quantitative determination of the cytotoxic agent piplartine (piperlongumine) in multiple skin layers. BIOMEDICAL CHROMATOGRAPHY, v. 33, n. 2 FEB 2019. Web of Science Citations: 1.

SPADARI, CRISTINA DE CASTRO; MENDES DA SILVA DE BASTIANI, FERNANDA WALT; LOPES, LUCIANA BIAGINI; ISHIDA, KELLY. Alginate nanoparticles as non-toxic delivery system for miltefosine in the treatment of candidiasis and cryptococcosis. INTERNATIONAL JOURNAL OF NANOMEDICINE, v. 14, p. 5187-5199, 2019. Web of Science Citations: 2.

JUNQUEIRA GARCIA, MARIA TERESA; GONCALVES, THALITA PEDRALINO; MARTINS, ERICKA SAO FELIX; MARTINS, TEREZA SILVA; DE ABREU FANTINI, MARCIA CARVALHO; REGAZI MINARINI, PAULO ROBERTO; FERNANDEZ, SANDRA COSTA; SALATA, GIOVANNA CASSONE; LOPES, LUCIANA BIAGINI. Improvement of cutaneous delivery of methylene blue by liquid crystals. International Journal of Pharmaceutics, v. 548, n. 1, p. 454-465, SEP 2018. Web of Science Citations: 5.

GIACONE, DANIELA V.; CARVALHO, VANESSA F. M.; COSTA, SORAIA K. P.; LOPES, LUCIANA B. Evidence That P-glycoprotein Inhibitor (Elacridar)-Loaded Nanocarriers Improve Epidermal Targeting of an Anticancer Drug via Absorptive Cutaneous Transporters Inhibition. Journal of Pharmaceutical Sciences, v. 107, n. 2, p. 698-705, FEB 2018. Web of Science Citations: 3.

CARVALHO, VANESSA F. M.; MIGOTTO, AMANDA; GIACONE, DANIELA V.; DE LEMOS, DEBORA P.; ZANONI, THALITA B.; MARIA-ENGLER, SILVYA S.; COSTA-LOTUFO, LETICIA V.; LOPES, LUCIANA B. Co-encapsulation of paclitaxel and C6 ceramide in tributyrin-containing nanocarriers improve co-localization in the skin and potentiate cytotoxic effects in 2D and 3D models. European Journal of Pharmaceutical Sciences, v. 109, p. 131-143, NOV 15 2017. Web of Science Citations: 9.

NG, WING Y.; MIGOTTO, AMANDA; FERREIRA, THAMYRES SOARES; LOPES, LUCIANA B. Monoolein-alginate beads as a platform to promote adenosine cutaneous localization and wound healing. International Journal of Biological Macromolecules, v. 102, p. 1104-1111, SEP 2017. Web of Science Citations: 5.

CARVALHO, VANESSA F.; DE LEMOS, DEBORA P.; VIEIRA, CAMILA S.; MIGOTTO, AMANDA; LOPES, LUCIANA B. Potential of Non-aqueous Microemulsions to Improve the Delivery of Lipophilic Drugs to the Skin. AAPS PHARMSCITECH, v. 18, n. 5, p. 1739-1749, JUL 2017. Web of Science Citations: 11.

SPADARI, CRISTINA DE CASTRO; LOPES, LUCIANA B.; ISHIDA, KELLY. Potential Use of Alginate-Based Carriers As Antifungal Delivery System. FRONTIERS IN MICROBIOLOGY, v. 8, JAN 30 2017. Web of Science Citations: 8.

PEPE, DOMINIQUE; CARVALHO, VANESSA F. M.; MCCALL, MELISSA; DE LEMOS, DEBORA P.; LOPES, LUCIANA B. Transportan in nanocarriers improves skin localization and antitumor activity of paclitaxel. INTERNATIONAL JOURNAL OF NANOMEDICINE, v. 11, p. 2009-2019, 2016. Web of Science Citations: 12.

LOPES, LUCIANA B.; GARCIA, MARIA TERESA J.; BENTLEY, MARIA VITORIA L. B. Chemical penetration enhancers. THERAPEUTIC DELIVERY, v. 6, n. 9, p. 1053-1061, SEP 2015. Web of Science Citations: 12.

LOPES, LUCIANA B.; CARVALHO, VANESSA F. M.; DE LEMOS, DEBORA P. Potential of Peptide-Based Enhancers for Transdermal Delivery. CURRENT PHARMACEUTICAL DESIGN, v. 21, n. 20, p. 2814-2822, 2015. Web of Science Citations: 5.