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Sustained drug delivery systems targeting the epithelial tissue

Grant number: 14/22451-7
Support type:Research Projects - Thematic Grants
Duration: September 01, 2015 - August 31, 2020
Field of knowledge:Health Sciences - Pharmacy
Principal Investigator:Renata Fonseca Vianna Lopez
Grantee:Renata Fonseca Vianna Lopez
Home Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
Co-Principal Investigators:Eduardo Melani Rocha ; Osvaldo de Freitas
Assoc. researchers:Flavio da Silva Emery ; Hamilton Cabral ; Karina Dias ; Marina Claro de Souza ; Patrícia Mazureki Campos ; Robert J Lee
Associated scholarship(s):19/19026-6 - Characterization of drug delivery systems and dosage of mediators in cell culture, BP.TT
19/14292-0 - Influence of iontophoresis and ultrasound on dendrimeric liquid crystals drug delivery, BP.PD
17/19193-4 - Evaluation of the effectiveness and safeness of a new formulation of cold cream in patients with atopic dermatitis, BP.MS
17/17442-7 - Evaluation of the low-frequency ultrasound potential for the sonodynamic therapy of skin cancer, BP.MS
17/05930-7 - Influence of iontophoresis and ultrasound on the release of drugs from dendrimeric liquid crystals, BP.PD


The aim of this proposal is to establish a platform for the development of topical delivery systems that ensure the targeted and sustained release of drugs to the epithelial tissue that forms the skin and the cornea. The design of drug delivery systems for topical treatment should take into account the integrity of the epithelium where they will be applied, the layer of this epithelium in which the disease is inserted, the physicochemical characteristics of the substances to be administered and the rate that these substances must be released to have the intended action. Due to the complexity to correlate all these variables, the project is divided into 2 parts. In the first one, delivery systems will be developed for application in non-intact epithelia, aimed at treating chronic wounds. The current market lacks products that combine substances that are effectives in the various stages of the healing process, that release these substances in a programmed period and that protect the wounds against physical and microbiological damage. Thus, the first part of this project proposes the development of delivery systems for macromolecules in a step, using fibroin based delivery systems, and for small molecules, but associated in a same system, in other step. The second part of the project aims at the development of delivery systems for application in intact and keratinized epithelia, such as skin tumors, where it is necessary to extrapolate the keratinized barrier and carry large quantities of active substance, released during long periods, for layers of the epithelium that require treatment. In this part of the project, the influence of iontophoresis and ultrasound in the release rate of drugs dispersed in liquid crystalline systems will be explored for the first time. (AU)

Articles published in Agência FAPESP Newsletter about the research grant
Group tests topical treatment strategy for fighting skin cancer  

Scientific publications (20)
(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)
GIL DE MELO, SHAIANI MARIA; DIAS DE REZENDE, LUCAS CUNHA; PETRILLI, RAQUEL; VIANNA LOPEZ, RENATA FONSECA; GOULART, MARILIA O. F.; EMERY, FLAVIO DA SILVA. Nitrosation of BODIPY dyes and their applications in the development of thiol sensors. DYES AND PIGMENTS, v. 173, FEB 2020. Web of Science Citations: 0.
CUBAYACHI, CAMILA; LEMOS, CAMILA NUNES; PEREIRA, FRANCIELI; DIAS, KARINA; HERCULANO, RONDINELLI DONIZETTI; DE FREITAS, OSVALDO; LOPEZ, RENATA F. V. Silk fibroin films stabilizes and releases bioactive insulin for the treatment of corneal wounds. EUROPEAN POLYMER JOURNAL, v. 118, p. 502-513, SEP 2019. Web of Science Citations: 1.
CRUZ-CAZARIM, ESTAEL L. C.; CAZARIM, MAURILIO S.; OGUNJIMI, ABAYOMI T.; PETRILLI, RAQUEL; ROCHA, EDUARDO M.; LOPEZ, V, RENATA F. Prospective insulin-based ophthalmic delivery systems for the treatment of dry eye syndrome and corneal injuries. EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS, v. 140, p. 1-10, JUL 2019. Web of Science Citations: 0.
GARCIA, DENNY MARCOS; DE OLIVEIRA, FABIOLA REIS; MODULO, CAROLINA MARIA; FAUSTINO, JACQUELINE; BARBOSA, AMANDA PIRES; ALVES, MONICA; ROCHA, EDUARDO MELANI. Is Sjogren's syndrome dry eye similar to dry eye caused by other etiologies? Discriminating different diseases by dry eye tests. PLoS One, v. 13, n. 12 DEC 3 2018. Web of Science Citations: 5.
DALMOLIN, LUCIANA FACCO; LOPEZ, V, RENATA F. Nanoemulsion as a Platform for Iontophoretic Delivery of Lipophilic Drugs in Skin Tumors. PHARMACEUTICS, v. 10, n. 4 DEC 2018. Web of Science Citations: 1.
NOMINATO, LUIS FERNANDO; DIAS, ANA CAROLINA; DIAS, LARA CRISTINA; FANTUCCI, MARINA ZILIO; COSTA MENDES DA SILVA, LILIAN ESLAINE; MURASHIMA, ADRIANA DE ANDRADE; ROCHA, EDUARDO MELANI. Prevention of Corneal Neovascularization by Adenovirus Encoding Human Vascular Endothelial Growth Factor Soluble Receptor (s-VEGFR1) in Lacrimal Gland. INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, v. 59, n. 15, p. 6036-6044, DEC 2018. Web of Science Citations: 1.
PETRILLI, RAQUEL; ELOY, JOSIMAR O.; SAGGIORO, FABIANO P.; CHESCA, DEISE L.; DE SOUZA, MARINA CLARO; DIAS, MARCOS V. S.; DASILVA, LUIS L. P.; LEE, ROBERT J.; LOPEZ, RENATA F. V. Skin cancer treatment effectiveness is improved by iontophoresis of EGFR-targeted liposomes containing 5-FU compared with subcutaneous injection. JOURNAL OF CONTROLLED RELEASE, v. 283, p. 151-162, AUG 10 2018. Web of Science Citations: 5.
REZENDE, LUCAS C. D.; MELO, SHAIANI M. G.; BOODTS, STIJN; VERBELEN, BRAM; EMERY, FLAVIO S.; DEHAEN, WIM. Thiocyanation of 3-substituted and 3,5-disubstituted BODIPYs and its application for the synthesis of new fluorescent sensors. DYES AND PIGMENTS, v. 154, p. 155-163, JUL 2018. Web of Science Citations: 7.
PETRILLO, R.; ELOY, J. O.; PASCHOAL, J. A. R.; LOPEZ, V, R. F. Quantification of 5-FU in skin samples for the development of new delivery systems for topical cancer treatment. Pharmazie, v. 73, n. 3, p. 133-138, MAR 2018. Web of Science Citations: 1.
PETRILLI, RAQUEL; VIANNA LOPEZ, RENATA FONSECA. Physical methods for topical skin drug delivery: concepts and applications. Brazilian Journal of Pharmaceutical Sciences, v. 54, n. SI 2018. Web of Science Citations: 0.
DO COUTO, RENE OLIVEIRA; CUBAYACHI, CAMILA; CALEFI, PAULO LINARES; VIANNA LOPEZ, RENATA FONSECA; PEDRAZZI, VINICIUS; DE GAITANI, CRISTIANE MASETTO; DE FREITAS, OSVALDO. Combining amino amide salts in mucoadhesive films enhances needle-free buccal anesthesia in adults. JOURNAL OF CONTROLLED RELEASE, v. 266, p. 205-215, NOV 28 2017. Web of Science Citations: 4.
GONTIJO, TALITA B.; DE FREITAS, ROSSIMIRIAM P.; EMERY, FLAVIO S.; PEDROSA, LEANDRO F.; VIEIRA NETO, JOSE B.; CAVALCANTI, BRUNO C.; PESSOA, CLAUDIA; KING, AARON; DE MOLINER, FABIO; VENDRELL, MARC; DA SILVA JUNIOR, EUFRNIO N. On the synthesis of quinone-based BODIPY hybrids: New insights on antitumor activity and mechanism of action in cancer cells. Bioorganic & Medicinal Chemistry Letters, v. 27, n. 18, p. 4446-4456, SEP 15 2017. Web of Science Citations: 7.
PEREIRA, TATIANA APARECIDA; RAMOS, DANIELLE NISHIDA; LOPEZ, RENATA F. V. Hydrogel increases localized transport regions and skin permeability during low frequency ultrasound treatment. SCIENTIFIC REPORTS, v. 7, MAR 13 2017. Web of Science Citations: 8.
OGUNJIMI, ABAYOMI T.; MELO, SHAIANI M. G.; VARGAS-RECHIA, CAREM G.; EMERY, FLAVIO S.; LOPEZ, RENATA F. V. Hydrophilic polymeric nanoparticles prepared from Delonix galactomannan with low cytotoxicity for ocular drug delivery. Carbohydrate Polymers, v. 157, p. 1065-1075, FEB 10 2017. Web of Science Citations: 12.
DE SANTANA, DANIELLE C. A. S.; DIAS, KARINA; SOUZA, JOEL G.; OGUNJIMI, ABAYOMI T.; SOUZA, MARINA C.; SILVA, ROBERTO S.; LOPEZ, RENATA F. V. NO Exchange for a Water Molecule Favorably Changes Iontophoretic Release of Ruthenium Complexes to the Skin. Molecules, v. 22, n. 1 JAN 2017. Web of Science Citations: 2.
PETRILLI, RAQUEL; ELOY, JOSIMAR O.; LOPEZ, RENATA F. V.; LEE, ROBERT J. Cetuximab Immunoliposomes Enhance Delivery of 5-FU to Skin Squamous Carcinoma Cells. ANTI-CANCER AGENTS IN MEDICINAL CHEMISTRY, v. 17, n. 2, p. 301-308, 2017. Web of Science Citations: 7.
BERNARDI, DANIELA S.; BITENCOURT, CLAUDIA; DA SILVEIRA, DENISE S. C.; DA CRUZ, ESTAEL L. C. M.; PEREIRA-DA-SILVA, MARCELO A.; FACCIOLI, LUCIA HELENA; LOPEZ, RENATA F. V. Effective transcutaneous immunization using a combination of iontophoresis and nanoparticles. Nanomedicine-Nanotechnology Biology and Medicine, v. 12, n. 8, p. 2439-2448, NOV 2016. Web of Science Citations: 12.
LEMOS, CAMILA NUNES; DE SOUZA, JOEL GONCALVES; SIMAO, PATRICIA SPER; VIANNA LOPEZ, RENATA FONSECA. Iontophoresis Improved Growth Reduction of Invasive Squamous Cell Carcinoma in Topical Photodynamic Therapy. PLoS One, v. 11, n. 1 JAN 11 2016. Web of Science Citations: 8.
GONTIJO, TALITA B.; DE FREITAS, ROSSIMIRIAM P.; DE LIMA, GUILHERME F.; DE REZENDE, LUCAS C. D.; PEDROSA, LEANDRO F.; SILVA, THAISSA L.; GOULART, MARILIA O. F.; CAVALCANTI, BRUNO C.; PESSOA, CLAUDIA; BRUNO, MARINA P.; CORREA, JOSE R.; EMERY, FLAVIO S.; DA SILVA JUNIOR, EUFRANIO N. Novel fluorescent lapachone-based BODIPY: synthesis, computational and electrochemical aspects, and subcellular localisation of a potent antitumour hybrid quinone. CHEMICAL COMMUNICATIONS, v. 52, n. 90, p. 13281-13284, 2016. Web of Science Citations: 14.

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