Sustained drug delivery systems targeting the epithelial tissue

• Grant number: 14/22451-7
• Support Opportunities: Research Projects - Thematic Grants
• Duration: September 01, 2015 - August 31, 2021
• Field of knowledge: Health Sciences - Pharmacy - Pharmaceutical Technology
• Principal Investigator: Renata Fonseca Vianna Lopez
• Grantee: Renata Fonseca Vianna Lopez
• Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Pesquisadores principais: Eduardo Melani Rocha ; Osvaldo de Freitas
• Associated researchers: Flavio da Silva Emery ; Hamilton Cabral ; Karina Dias ; Marina Claro de Souza ; Patrícia Mazureki Campos ; Robert J Lee
• Associated scholarship(s): 19/25710-7 - Investigation of bacteriostatic effect of iontophoresis in Gram positives and Gram negatives bacterias, BP.IC; 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; + associated scholarships 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 - associated scholarships

Abstract

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)

Scientific publications

(40)

(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)

AMANDA PIRES BARBOSA; MONICA ALVES; JOÃO MARCELLO FORTES FURTADO; LEIDIANE ADRIANO; LUIS FERNANDO NOMINATO; LARA CRISTINA DIAS; MARINA ZILIO FANTUCCI; ADRIANA DE ANDRADE BATISTA MURASHIMA; EDUARDO MELANI ROCHA. A cegueira corneal na caverna de Platão: as forças para prevenir e reverter a opacidade da córnea. Parte I: epidemiologia e novos conceitos na fisiopatologia. Arquivos Brasileiros de Oftalmologia, v. 83, n. 5, p. 437-446, 2020-10-08. (14/22451-7)

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. (12/05177-3, 14/07125-6, 11/13307-1, 14/22451-7)

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. (14/22451-7)

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. (14/22451-7, 13/15134-2, 12/23764-3)

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. (14/18973-8, 11/23342-9, 14/22451-7)

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. (11/21411-3, 14/22451-7)

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. (14/22451-7)

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. (10/20794-3, 14/22451-7, 11/06202-9)

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. (13/15134-2, 12/23764-3, 14/22451-7)

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. (12/07251-6, 12/05644-0, 13/12174-3, 14/22451-7, 12/06167-1)

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. (14/22451-7)

SILVA FAVACHO, HUGO ALEXANDRE; DO COUTO, RENE OLIVEIRA; FERREIRA DUARTE, MAIRA PERES; GAROFO PEIXOTO, MARIA PAULA; VIANNA LOPEZ, RENATA FONSECA; PEDRAZZI, VINICIUS; DE GAITANI, CRISTIANE MASETTO; DE FREITAS, OSVALDO. Synergy between surfactants and mucoadhesive polymers enhances the transbuccal permeation of local anesthetics from freeze-dried tablets. Materials Science & Engineering C-Materials for Biological Applications, v. 108, MAR 2020. (12/05644-0, 12/06167-1, 12/07251-6, 13/12174-3, 14/22451-7)

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. (14/23211-0, 14/22451-7)

CAMPOS, PATRICIA MAZUREKI; PETRILLI, RAQUEL; LOPEZ, V, RENATA F.. The prominence of the dosage form design to treat ocular diseases. International Journal of Pharmaceutics, v. 586, AUG 30 2020. (17/05930-7, 14/50928-2, 14/22451-7)

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. (14/22451-7, 14/19018-0)

SHIKIDA, DANIELLE NISHIDA RAMOS; DALMOLIN, LUCIANA FACCO; FUMAGALLI, FERNANDO; EMERY, FLAVIO DA SILVA; LOPEZ, V, RENATA F.. Arginine-conjugated chitosan nanoparticles for topical arginine release in wounds. JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY, v. 61, FEB 2021. (14/50928-2, 14/22451-7)

MARTINS, YUGO ARAUJO; PAVAN, THEO ZEFERINO; LOPEZ, RENATA FONSECA VIANNA. Sonodynamic therapy: Ultrasound parameters and in vitro experimental configurations. International Journal of Pharmaceutics, v. 610, DEC 15 2021. (17/17442-7, 14/22451-7)

OLIVEIRA, CAROLINA G.; DALMOLIN, LUCIANA F.; SILVA, R. T. C.; LOPEZ, V, RENATA F.; MAIA, PEDRO I. S.; MORETO, JEFERSON A.. PLGA-nanoparticles loaded with a thiosemicarbazone derived palladium(ii) complex as a potential agent to new formulations for human ovarian carcinoma treatment. NEW JOURNAL OF CHEMISTRY, v. 44, n. 35, p. 14928-14935, SEP 21 2020. (14/22451-7)

MARTINS, YUGO A.; FONSECA, V, MARIA J.; PAVAN, THEO Z.; LOPEZ, V, RENATA F.. Bifunctional Therapeutic Application of Low-Frequency Ultrasound Associated with Zinc Phthalocyanine-Loaded Micelles. INTERNATIONAL JOURNAL OF NANOMEDICINE, v. 15, p. 8075-8095, 2020. (14/22451-7, 17/17442-7, 14/50928-2)

DIAS, LARA CRISTINA; ZHENG, CHANGYU; MURASHIMA, ADRIANA DE ANDRADE BATISTA; DIAS, ANA CAROLINA; FANTUCCI, MARINA ZILIO; NOMINATO, LUIZ FERNANDO; DA SILVA, LILIAN ESLAINE COSTA MENDES; ROCHA, EDUARDO MELANI. Lacrimal Gland as a Target Organ for Adenovirus Gene Therapy Encoding Erythropoietin for Dry Eye Induced by Benzalkonium Chloride. CURRENT EYE RESEARCH, v. 46, n. 9, p. 1314-1319, SEP 2 2021. (14/22451-7)

DO COUTO, RENE OLIVEIRA; CUBAYACHI, CAMILA; DUARTE, MAIRA PERES FERREIRA; LOPEZ, RENATA FONSECA VIANNA; PEDRAZZI, VINICIUS; GAITANI, CRISTIANE MASETTO DE; FREITAS, OSVALDO DE. Towards the advance of a novel iontophoretic patch for needle-free buccal anesthesia. Materials Science & Engineering C-Materials for Biological Applications, v. 122, MAR 2021. (12/05644-0, 14/22451-7, 13/12174-3)

ADAMI, LARISSE EDUARDO; DE FREITAS, OSVALDO; TOCCHINI DE FIGUEIREDO, FELLIPE AUGUSTO; FERREIRA, MAIRA PERES; MACEDO, ANA PAULA; DO COUTO, RENE OLIVEIRA; PEDRAZZI, VINICIUS. Needle-free anesthesia: clinical efficacy of a mucoadhesive patch for atraumatic anesthesia in dental procedures. Brazilian Oral Research, v. 35, 2021. (14/22451-7)

ANTUNES-FOSCHINI, ROSALIA; ADRIANO, LEIDIANE; BATISTA MURASHIMA, ADRIANA DE ANDRADE; BARBOSA, AMANDA PIRES; NOMINATO, LUIS FERNANDO; DIAS, LARA CRISTINA; FANTUCCI, MARINA ZILIO; GARCIA, DENNY MARCOS; ALVES, MONICA; ROCHA, EDUARDO MELANI. Limitações e avanços em novos tratamentos e perspectivas futuras na cegueira corneal. Arquivos Brasileiros de Oftalmologia, v. 84, n. 3, p. 282-296, MAY-JUN 2021. (14/22451-7)

AMANDA PIRES BARBOSA; FABÍOLA REIS DE OLIVEIRA; FLAVIO JAIME DA ROCHA; VALDAIR FRANCISCO MUGLIA; EDUARDO MELANI ROCHA. Lacrimal gland atrophy and dry eye related to isotretinoin, androgen, and prolactin: differential diagnosis for Sjogren's syndrome. Arquivos Brasileiros de Oftalmologia, v. 84, n. 1, p. 78-82, Jan. 2021. (14/23211-0, 14/22451-7)

OGUNJIMI, ABAYOMI TOLULOPE; CHAHUD, FERNANDO; LOPEZ, RENATA F. V.. Isotretinoin-Delonix polymeric nanoparticles: Potentials for skin follicular targeting in acne treatment. International Journal of Pharmaceutics, v. 610, DEC 15 2021. (14/22451-7, 14/50928-2)

JACQUELINE FERREIRA FAUSTINO BARROS; ARIANE MIRELA SARANZO SANT'ANA; LARA CRISTINA DIAS; ADRIANA DE ANDRADE BATISTA MURASHIMA; LILIAN ESLAINE COSTA MENDES DA SILVA; MARINA ZILIO FANTUCCI; EDUARDO MELANI ROCHA. Comparação dos efeitos da denervação da córnea e da glândula lacrimal na unidade funcional lacrimal de ratos. Arquivos Brasileiros de Oftalmologia, v. 85, n. 1, p. 59-67, 2021-09-10. (14/22451-7, 14/23211-0)

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. (14/22451-7)

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. (13/50677-7, 14/18973-8, 11/23342-9, 14/22451-7, 17/21146-4)

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.; et al. 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. (14/22451-7)

BARBOSA, AMANDA PIRES; ALVES, MONICA; FORTES FURTADO, JOAO MARCELLO; ADRIANO, LEIDIANE; NOMINATO, LUIS FERNANDO; DIAS, LARA CRISTINA; FANTUCCI, MARINA ZILIO; BATISTA MURASHIMA, ADRIANA DE ANDRADE; ROCHA, EDUARDO MELANI. Corneal blindness in Plato's cave: the acting forces to prevent and revert corneal opacity. Part I: epidemiology and new physiopathological concepts. Arquivos Brasileiros de Oftalmologia, v. 83, n. 5, p. 437-446, SEP-OCT 2020. (14/22451-7)

LEIDIANE ADRIANO; ETIENE LORRIANE DE SOUZA PERSONA; ISVANDER GUSTAVO DE SOUZA PERSONA; REGINA CELIA NUCCI PONTELLI; EDUARDO M. ROCHA. Correlação entre o pterígio presumível com olho seco e com fatores de risco sistêmicos e oculares. Arquivos Brasileiros de Oftalmologia, v. 85, n. 2, p. 136-143, 2021-08-18. (14/22451-7)

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. (16/03584-1, 14/22451-7)

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. (17/05930-7, 14/22451-7)

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; et al. 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. (14/22451-7)

LEMOS, CAMILA NUNES; CUBAYACHI, CAMILA; DIAS, KARINA; MENDONCA, JACQUELINE NAKAU; LOPES, NORBERTO PEPORINE; JACOMETTI CARDOSO FURTADO, NIEGE ARACARI; LOPEZ, V, RENATA F.. Iontophoresis-stimulated silk fibroin films as a peptide delivery system for wound healing. EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS, v. 128, p. 147-155, JUL 2018. (14/22451-7)

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. (14/22451-7, 13/15134-2, 12/23764-3)

MARTIN, BIANCA APARECIDA; LEMOS, CAMILA NUNES; DALMOLIN, LUCIANA FACCO; ARRUDA, CAROLINE; BRAIT, IRIS SPERCHI CAMILO; CAZARIM, MAURILIO DE SOUZA; DA CRUZ-CAZARIM, ESTAEL LUZIA COELHO; BUENO, PAULA CAROLINA PIRES; JUNIOR, MAURILIO POLIZELLO; PEREIRA, LEONARDO REGIS LEIRA; et al. A New Approach to Atopic Dermatitis Control with Low-Concentration Propolis-Loaded Cold Cream. PHARMACEUTICS, v. 13, n. 9, SEP 2021. (17/19193-4, 14/22451-7)

LEIDIANE ADRIANO; ETIENE LORRIANE DE SOUZA PERSONA; ISVANDER GUSTAVO DE SOUZA PERSONA; REGINA CELIA NUCCI PONTELLI; EDUARDO M. ROCHA. Correlation between the presumed pterygium with dry eye and with systemic and ocular risk factors. Arquivos Brasileiros de Oftalmologia, n. ahead, p. -, 2021. (14/22451-7)

MARTINS, YUGO ARAUJO; GONCALVES, TALITA MOTA; LOPEZ, RENATA F. V.. HPLC methods for choloroquine determination in biological samples and pharmaceutical products. DARU-JOURNAL OF PHARMACEUTICAL SCIENCES, v. 29, n. 1, MAR 2021. (14/22451-7)

DIAS, LARA CRISTINA; ZHENG, CHANGYU; MURASHIMA, ADRIANA DE ANDRADE BATISTA; DIAS, ANA CAROLINA; FANTUCCI, MARINA ZILIO; NOMINATO, LUIZ FERNANDO; DA SILVA, LILIAN ESLAINE COSTA MENDES; ROCHA, EDUARDO MELANI. Lacrimal Gland as a Target Organ for Adenovirus Gene Therapy Encoding Erythropoietin for Dry Eye Induced by Benzalkonium Chloride. CURRENT EYE RESEARCH, APR 2021. (14/22451-7)