Lipid-based nanocarriers (SLN/NLC and remote-loading liposomes) used to improve the upload and potency of local anesthetics

• Grant number: 14/14457-5
• Support Opportunities: Research Projects - Thematic Grants
• Start date: September 01, 2014
• End date: November 30, 2019
• Field of knowledge: Biological Sciences - Pharmacology - Biochemical and Molecular Pharmacology
• Principal Investigator: Eneida de Paula
• Grantee: Eneida de Paula
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Pesquisadores principais: Daniele Ribeiro de Araujo ; Michelle Franz Montan Braga Leite
• Associated researchers: Giovana Tofoli Moniz ; Laura de Oliveira Nascimento ; Luís Fernando Cabeça ; Marcelo Lancellotti ; Michelle Franz Montan Braga Leite ; Theo Guenter Kieckbusch
• Associated research grant(s): 18/15293-7 - Development of controlled topical release formulations of the antimicrobian ciprofloxacin in ordered mesoporous silica and clays, AP.R SPRINT; 18/05052-2 - 25th Nano Congress for Future Advancements, AR.EXT; 14/20224-3 - Multiuser equipment approved in grant # 2014/14457-5: PILOT shelf freeze-dryer, AP.EMU; 14/18335-1 - Multiuser equipment approved in grant # 2014/14457-5: particle tracking analyzer and zeta POTENTIAL/DYNAMIC light scattering, AP.EMU
• Associated scholarship(s): 19/14773-8 - Organogels lecitin-poloxamer-based for skin delivery: development, ex vivo permeation profile and stratum corneum structural evaluation, BP.DD; 19/15157-9 - Preparation and structural characterization of thermosensitive natural oils-based organogels, BP.IC; 19/07245-5 - Lidocaine and epinephrine co-loaded mucoadhesive liquid crystal precursor systems as a strategy for topical anesthesia in the buccal cavity, BP.PD; + associated scholarships 18/25920-9 - Thermoreversible hydrogel containing tetracaine loaded in nanostructured lipid carriers for topical intranasal delivery, BP.PD; 18/04036-3 - Organogels LECITIN-POLOXAMER-BASED for skin delivery: development, ex vivo permeation profile and stratum corneum structural evaluation, BP.MS; 18/12870-3 - Evaluation of poloxamer-based ropivacaine gel formulations in a post operative pain model, BP.IC; 18/12121-0 - LIPID-BASED NANOCARRIERS FOR THE LOCAL ANESTHETIC TETRACAINE, BP.PD; 18/07100-4 - Citotoxicity and in vivo anesthesia effect of functional nanostructured lipid carriers loaded with S75:R25 bupivacaine, designed for burn treatment, BP.IC; 17/24402-1 - pH AND TEMPERATURE SENSITIVE DRUG NANOCARRIERS FOR SKIN APPLICATIONS, BP.PD; 18/02482-6 - Preparation and characterization of nanostructured lipid organogels as skin-drug delivery systems, BP.IC; 17/15174-5 - Development of functional lipid nanoparticles for the improvement of the anesthetic potency at inflamed tissues, BP.DR; 17/06613-5 - Development of biopolymeric wafers for buccal administration of local anesthetics, BP.IC; 17/05136-9 - In vitro performance of xantan hydrogels containing local anesthetic encapsulated in nanostructured lipid carriers for topical application at oral mucosa, BP.IC; 16/04158-6 - Development and characterization of functional lipid-biopolymeric films for lidocaine transdermal delivery, BP.IC; 16/00463-9 - Sustained-release formulation development for tetracaine encapsulated in ionic gradient liposomes, BP.PD; 15/26189-8 - Development of nanostructured lipid carriers functionalized with hyaluronic acid for local anesthetics modified release by intra-articular route, BP.PD; 15/14763-1 - Poloxamer-hyaluronic acid hydrogels as sulforaphane delivery systems for the osteoarthritis treatment., BP.DR; 15/11804-9 - Local anesthetic combined with capsaicin:hydroxypropyl-beta-cyclodextrin inclusion complex to selective increase the anesthetic potency, BP.DR; 14/25372-0 - Development of nanostructured lipid carriers encapsulating local anesthetics processed biopolymeric matrices for topical application at oral mucosa, BP.PD - associated scholarships

Abstract

Local anesthetics (LA) are amphiphile compounds that interact with the sodium channel protein reversibly blocking the action potential of excitable membranes. The more potent the anesthetic (as for instance bupivacaine, which is the drug-of-choice for surgical procedures) the more toxic it is to the Central Nervous and Cardiovascular systems. Our research group has been working in the development of sustained release systems for local anesthetics, with encouraging results in animals and human, regarding the use of liposomes, cyclodextrins and polymers as drug delivery systems (de Paula E. et al., Exp. Op. Drug Delivery 9:1505, 2012). Liposomes are the most well-known drug-delivery system but they have a limited encapsulation efficiency caused by the low amounts used for injection (ca. 10-2 M lipids, i.e. in the same magnitude of LA clinical doses). Such limitation curbs liposomes use as quantitative LA reservoirs for sustained release purposes. Here we intend to employ two novel drug-delivery strategies to enhance the encapsulation of long acting LA such as bupivacaine (e.g., ropivacaine, dibucaine, tetracaine, etidocaine&) by preparing and characterizing: 1) ion-gradient (or remote-loading) liposomes and 2) Nanostructured lipid carriers (SLN/NLC), able to upload higher amount of LA in the particle core. Two approaches will be adopted to form the ionic gradient: kosmotropic ions such as sufalte and citrate and acid medium in the liposomes core. Liposome type (uni or multivesicullar) and composition will be also evaluated in terms of their effect on the sustained LA delivery since there is a report in the literature of as much as 48h anesthesia after intradermic bupivacaine injection in humans (Grant GJ et al., Anesthesiol. 101:133, 2004). Solid lipid nanoparticles and nanostructured lipid carriers will be prepared through high pressure hot homogenization or sonication, from solid matrices of cetyl palmitate or myristyl myristate plus Pluronic F68 as a colloidal stabilizer; LiponateGC (a mixture of triglycerides of caprylic and capric acids) will sere as the liquid lipid component of NLC. The in vitro and in vivo effect of the formulations will be compared to those evoked by the equivalent commercial product of the LA. Looking forward the development of pharmaceutical products, pharmacokinectic studies, lyoprotection tests for shelf-life extension and hydrogel preparations for parental and topic uses will be performed. These innovative and of technological potential approaches will provide significant increase in the upload of anesthetic in the lipid-based particles, prolonging the anesthesia duration of action to avoid the need for re-administration in the (surgical or post-operative procedures) treatment of pain. (AU)

Scientific publications

(57)

(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)

COUTO, VERONICA M.; PRIETO, MARIA J.; IGARTUA, DANIELA E.; FEAS, DANIELA A.; RIBEIRO, LIGIA N. M.; SILVA, CAMILA M. G.; CASTRO, SIMONE R.; GUILHERME, VIVIANE A.; DANTZGER, DARLENE D.; MACHADO, DAISY; et al. Dibucaine in Ionic-Gradient Liposomes: Biophysical, Toxicological, and Activity Characterization. Journal of Pharmaceutical Sciences, v. 107, n. 9, p. 2411-2419, SEP 2018. (13/13965-4, 14/14457-5)

DE MORAIS RIBEIRO, LIGIA NUNES; FRANZ-MONTAN, MICHELLE; BREITKREITZ, MARCIA CRISTINA; RODRIGUES DA SILVA, GUSTAVO HENRIQUE; DE CASTRO, SIMONE RAMOS; GUILHERME, VIVIANE APARECIDA; DE ARAUJO, DANIELE RIBEIRO; DE PAULA, ENEIDA. Nanohybrid hydrogels designed for transbuccal anesthesia. INTERNATIONAL JOURNAL OF NANOMEDICINE, v. 13, p. 6453-6463, 2018. (14/14457-5, 14/25372-0)

SANTOS AKKARI, ALESSANDRA CRISTINA; RAMOS CAMPOS, ESTEFANIA VANGELIE; KEPPLER, ARTUR FRANZ; FRACETO, LEONARDO FERNANDES; DE PAULA, ENEIDA; TOFOLI, GIOVANA RADOMILLE; DE ARAUJO, DANIELE RIBEIRO. Budesonide-hydroxypropyl-beta-cyclodextrin inclusion complex in binary poloxamer 407/403 system for ulcerative colitis treatment: A physico-chemical study from micelles to hydrogels. COLLOIDS AND SURFACES B-BIOINTERFACES, v. 138, p. 138-147, FEB 1 2016. (14/26200-9, 14/14457-5)

RIBEIRO, LIGIA N. M.; BREITKREITZ, MARCIA C.; GUILHERME, VIVIANE A.; DA SILVA, GUSTAVO H. R.; COUTO, VERONICA M.; CASTRO, SIMONE R.; DE PAULA, BARBARA O.; MACHADO, DAISY; DE PAULA, ENEIDA. Natural lipids-based NLC containing lidocaine: from pre-formulation to in vivo studies. European Journal of Pharmaceutical Sciences, v. 106, p. 102-112, AUG 30 2017. (14/14457-5, 14/25372-0)

GONCALVES DA SILVA, CAMILA MORAIS; FRANZ-MONTAN, MICHELLE; GOMEZ LIMIA, CINTIA ELISABETH; DE MORAIS RIBEIRO, LIGIA NUNES; BRAGA, MARIO ANTONIO; GUILHERME, VIVIANE APARECIDA; DA SILVA, CAMILA BATISTA; CASADEI, BRUNA RENATA; SAIA CEREDA, CINTIA MARIA; DE PAULA, ENEIDA. Encapsulation of ropivacaine in a combined (donor-acceptor, ionic-gradient) liposomal system promotes extended anesthesia time. PLoS One, v. 12, n. 10, OCT 5 2017. (11/21735-3, 14/14457-5)

DE MORAIS RIBEIRO, LIGIA NUNES; COUTO, VERONICA MUNIZ; FRACETO, LEONARDO FERNANDES; DE PAULA, ENEIDA. Use of nanoparticle concentration as a tool to understand the structural properties of colloids. SCIENTIFIC REPORTS, v. 8, JAN 17 2018. (14/14457-5, 14/25372-0)

PEDREIRA DE ALMEIDA, ANA CLAUDIA; ALVES PINTO, LUCIANA MATOS; ALVES, GIULIANA PIOVESAN; DE MORAIS RIBEIRO, LIGIA NUNES; ANDRADE SANTANA, MARIA HELENA; SAIA CEREDA, CINTIA MARIA; FRACETO, LEONARDO FERNANDES; DE PAULA, ENEIDA. Liposomal-based lidocaine formulation for the improvement of infiltrative buccal anaesthesia. Journal of Liposome Research, v. 29, n. 1, p. 66-72, 2019. (14/14457-5)

GUILHERME, VIVIANE A.; RIBEIRO, LIGIA N. M.; TOFOLI, GIOVANA RADOMILLE; FRANZ-MONTAN, MICHELLE; DE PAULA, ENEIDA; DE JESUS, MARCELO BISPO. Current Challenges and Future of Lipid Nanoparticles Formulations for Topical Drug Application to Oral Mucosa, Skin, and Eye. CURRENT PHARMACEUTICAL DESIGN, v. 23, n. 43, p. 6659-6675, 2017. (14/03002-7, 14/14457-5)

BARBOSA, RAQUEL M.; CASADEI, BRUNA R.; DUARTE, EVANDRO L.; SEVERINO, PATRICIA; BARBOSA, LEANDRO R. S.; DURAN, NELSON; DE PAULA, ENEIDA. Electron Paramagnetic Resonance and Small-Angle X-ray Scattering Characterization of Solid Lipid Nanoparticles and Nanostructured Lipid Carriers for Dibucaine Encapsulation. Langmuir, v. 34, n. 44, p. 13296-13304, NOV 6 2018. (14/14457-5)

FREITAS MARIANO, KELLI CRISTINA; BOAVA PAPINI, JULIANA ZAMPOLI; DE FARIA, NAIALLY CARDOSO; CABRAL HELUANY, DANIELE NICOLI; LOURENCONI BOTEGA, ANA LUIZA; SAIA CEREDA, CINTIA MARIA; DE PAULA, ENEIDA; TOFOLI, GIOVANA RADOMILLE; DE ARAUJO, DANIELE RIBEIRO. Ropivacaine-Loaded Poloxamer Binary Hydrogels for Prolonged Regional Anesthesia: Structural Aspects, Biocompatibility, and Pharmacological Evaluation. BIOMED RESEARCH INTERNATIONAL, v. 2021, SEP 16 2021. (14/14457-5)

SCRIBONI, ANDREIA BORGES; COUTO, VERONICA MUNIZ; DE MORAIS RIBEIRO, LIGIA NUNES; FREIRES, IRLAN ALMEIDA; GROPPO, FRANCISCO CARLOS; DE PAULA, ENEIDA; FRANZ-MONTAN, MICHELLE; COGO-MULLER, KARINA. Fusogenic Liposomes Increase the Antimicrobial Activity of Vancomycin Against Staphylococcus aureus Biofilm. FRONTIERS IN PHARMACOLOGY, v. 10, NOV 29 2019. (14/14457-5)

RIBEIRO COSTA, JULIANA SOUZA; CRUVINEL, KAREN DE OLIVEIRA; OLIVEIRA-NASCIMENTO, LAURA. A mini-review on drug delivery through wafer technology: Formulation and manufacturing of buccal and oral lyophilizates. JOURNAL OF ADVANCED RESEARCH, v. 20, p. 33-41, NOV 2019. (17/06613-5, 14/14457-5)

FREITAS MARIANO, KELLI C.; MONTEIRO DO NASCIMENTO, MONICA H.; QUEROBINO, SAMYR M.; RAMOS CAMPOS, V, ESTEFANIA; DE OLIVEIRA, JHONES L.; YOKAICHIYA, FABIANO; FRANCO, MARGARETH K. K. D.; ALBERTO-SILVA, CARLOS; DE PAULA, ENEIDA; LOMBELLO, CHRISTIANE B.; et al. Influence of chitosan-tripolyphosphate nanoparticles on thermosensitive polymeric hydrogels: structural organization, drug release mechanisms and cytotoxicity. INTERNATIONAL JOURNAL OF POLYMERIC MATERIALS, v. 69, n. 9, p. 592-603, JUN 12 2020. (14/14457-5, 14/12653-1, 14/26200-9)

RODRIGUES DA SILVA, GUSTAVO H.; GERONIMO, GABRIELA; RIBEIRO, LIGIA N. M.; GUILHERME, VIVIANE A.; DE MOURA, LUDMILLA DAVID; BOMBEIRO, ANDRE L.; OLIVEIRA, JULIANA DAMASCENO; BREITKREITZ, MARCIA C.; DE PAULA, ENEIDA. Injectable in situ forming nanogel: A hybrid Alginate-NLC formulation extends bupivacaine anesthetic effect. Materials Science & Engineering C-Materials for Biological Applications, v. 109, APR 2020. (18/07100-4, 14/25372-0, 17/15174-5, 14/14457-5)

GRILLO, RENATO; DIAS, V, FABIANA; QUEROBINO, SAMYR M.; ALBERTO-SILVA, CARLOS; FRACETO, LEONARDO F.; DE PAULA, ENEIDA; DE ARAUJOL, DANIELE R.. Influence of hybrid polymeric nanoparticle/thermosensitive hydrogels systems on formulation tracking and in vitro artificial membrane permeation: A promising system for skin drug-delivery. COLLOIDS AND SURFACES B-BIOINTERFACES, v. 174, p. 56-62, FEB 1 2019. (15/26189-8, 14/14457-5)

ALBANO, JUAN M. R.; DE MORAIS RIBEIRO, LIGIA NUNES; COUTO, VERONICA MUNIZ; MESSIAS, MARIANA BARBOSA; RODRIGUES DA SILVA, GUSTAVO HENRIQUE; BREITKREITZ, MARCIA CRISTINA; DE PAULA, ENEIDA; PICKHOLZ, MONICA. Rational design of polymer-lipid nanoparticles for docetaxel delivery. COLLOIDS AND SURFACES B-BIOINTERFACES, v. 175, p. 56-64, MAR 1 2019. (14/14457-5, 14/25372-0)

FERNANDES, PRISCILA CORDEIRO LIMA; DE MOURA, LUDMILLA DAVID; DE LIMA, FERNANDO FREITAS; DA SILVA, GUSTAVO HENRIQUE RODRIGUES; SOUZA, ROOSEVELT ISAIAS CARVALHO; DE PAULA, ENEIDA. Lipid nanocapsules loaded with prilocaine and lidocaine and incorporated in gel for topical application. International Journal of Pharmaceutics, v. 602, JUN 1 2021. (14/14457-5)

COUTO, VERONICA MUNIZ; DE OLIVEIRA-NASCIMENTO, LAURA; CABECA, LUIZ FERNANDO; GERALDES, DANILO COSTA; RIBEIRO COSTA, JULIANA SOUZA; RISKE, KARIN A.; FRANZ-MONTAN, MICHELLE; YOKAYCHIYA, FABIANO; DIAS FRANCO, MARGARETH K. K.; DE PAULA, ENEIDA. Capsaicin-Cyclodextrin Complex Enhances Mepivacaine Targeting and Improves Local Anesthesia in Inflamed Tissues. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 21, n. 16, AUG 2020. (14/20224-3, 15/11804-9, 14/14457-5)

PRATES, ERICA TEIXEIRA; RODRIGUES DA SILVA, GUSTAVO HENRIQUE; SOUZA, THAIS F.; SKAF, MUNIR S.; PICKHOLZ, MONICA; DE PAULA, ENEIDA. Articaine interaction with phospholipid bilayers. Journal of Molecular Structure, v. 1222, DEC 15 2020. (14/14457-5, 17/15174-5, 07/02629-2)

RIBEIRO, LIGIA N. M.; FRANZ-MONTAN, MICHELLE; ALCANTARA, ANA C. S.; BREITKREITZ, MARCIA C.; CASTRO, SIMONE R.; GUILHERME, VIVIANE A.; MUNIZ, V, BRUNO; RODRIGUES DA SILVA, GUSTAVO H.; DE PAULA, ENEIDA. Hybrid nanofilms as topical anesthetics for pain-free procedures in dentistry. SCIENTIFIC REPORTS, v. 10, n. 1, JUL 9 2020. (14/50867-3, 14/25372-0, 14/14457-5)

RODRIGUES DA SILVA, GUSTAVO H.; MENDES, LUIS F.; DE CARVALHO, FABIOLA, V; DE PAULA, ENEIDA; DUARTE, IOLA F.. Comparative Metabolomics Study of the Impact of Articaine and Lidocaine on the Metabolism of SH-SY5Y Neuronal Cells. METABOLITES, v. 12, n. 7, p. 17-pg., 2022-07-01. (14/14457-5, 18/24814-0, 19/17784-0)

OLIVEIRA, JULIANA DAMASCENO; RODRIGUES DA SILVA, GUSTAVO HENRIQUE; DE MOURA, LUDMILA DAVID; GOETHEL, GABRIELA; PAPINI, JULIANA Z. B.; CASADEI, BRUNA RENATA; DE MORAIS RIBEIRO, LIGIA NUNES; CABECA, LUIS FERNANDO; GARCIA, SOLANGE CRISTINA; MARTINEZ, ELIZABETH FERREIRA; et al. DoE development of ionic gradient liposomes: A successful approach to improve encapsulation, prolong anesthesia and decrease the toxicity of etidocaine. International Journal of Pharmaceutics, v. 634, p. 12-pg., 2023-02-06. (14/14457-5)

RIBEIRO, LIGIA N. M.; ALCANTARA, ANA C. S.; RODRIGUES DA SILVA, GUSTAVO H.; FRANZ-MONTAN, MICHELLE; NISTA, SILVIA V. G.; CASTRO, SIMONE R.; COUTO, VERONICA M.; GUILHERME, VIVIANE A.; DE PAULA, ENEIDA. Advances in Hybrid Polymer-Based Materials for Sustained Drug Release. INTERNATIONAL JOURNAL OF POLYMER SCIENCE, v. 2017, p. 16-pg., 2017-01-01. (14/25372-0, 14/14457-5)

ALVES, DANILO ANTONINI; MACHADO, DAISY; MELO, ADRIANA; CARNEIRO PEREIRA, RAFAELLA FABIANA; SEVERINO, PATRICIA; DE HOLLANDA, LUCIANA MARIA; ARAUJO, DANIELE RIBEIRO; LANCELLOTTI, MARCELO. Preparation of Thermosensitive Gel for Controlled Release of Levofloxacin and Their Application in the Treatment of Multidrug-Resistant Bacteria. BIOMED RESEARCH INTERNATIONAL, v. 2016, p. 10-pg., 2016-01-01. (11/21822-3, 11/21685-6, 14/14457-5)

RIBEIRO, LIGIA N. M.; ALCANTARA, ANA C. S.; RODRIGUES DA SILVA, GUSTAVO H.; FRANZ-MONTAN, MICHELLE; NISTA, SILVIA V. G.; CASTRO, SIMONE R.; COUTO, VERONICA M.; GUILHERME, VIVIANE A.; DE PAULA, ENEIDA. Advances in Hybrid Polymer-Based Materials for Sustained Drug Release. INTERNATIONAL JOURNAL OF POLYMER SCIENCE, 2017. (14/14457-5, 14/25372-0)

ALVES, DANILO ANTONINI; MACHADO, DAISY; MELO, ADRIANA; CARNEIRO PEREIRA, RAFAELLA FABIANA; SEVERINO, PATRICIA; DE HOLLANDA, LUCIANA MARIA; ARAUJO, DANIELE RIBEIRO; LANCELLOTTI, MARCELO. Preparation of Thermosensitive Gel for Controlled Release of Levofloxacin and Their Application in the Treatment of Multidrug-Resistant Bacteria. BIOMED RESEARCH INTERNATIONAL, 2016. (11/21685-6, 14/14457-5, 11/21822-3)

GERONIMO, GABRIELA; RODRIGUES DA SILVA, GUSTAVO H.; DE MOURA, LUDMILLA D.; RIBEIRO, LIGIA N. M.; GUILHERME, VIVIANE A.; MENDONCA, TALITA C.; CASTRO, SIMONE R.; BREITKREITZ, MARCIA C.; DE PAULA, ENEIDA. Development of S75:R25 bupivacaine-loaded lipid nanoparticles functionalized with essential oils for treating melanoma. JOURNAL OF CHEMICAL TECHNOLOGY AND BIOTECHNOLOGY, v. 96, n. 8, p. 2197-2207, AUG 2021. (14/14457-5, 18/07100-4, 17/15174-5)

FURLAN, BEATRIZ; DE MELO, BEATRIZ T.; PAPINI, JULIANA Z. B.; SPERANDIO, MARCELO; OLIVEIRA, JULIANA D.; DE PAULA, ENEIDA; CEREDA, CINTIA M. S.; TOFOLI, GIOVANA R.. Pre-clinical evaluation of new dibucaine formulations for preventive analgesia. Journal of Liposome Research, v. 31, n. 3, p. 230-236, JUL 3 2021. (14/14457-5)

VIGATO, ARYANE ALVES; QUEROBINO, SAMYR MACHADO; DE FARIA, NAIALLY CARDOSO; BOLELA BOVO CANDIDO, ANA CAROLINA; MAGALHAES, LIZANDRA GUIDI; SAIA CEREDA, CINTIA MARIA; TOFOLI, GIOVANA RADOMILLE; RAMOS CAMPOS, ESTEFANIA VANGELIE; MACHADO, IAN POMPERMAYER; FRACETO, LEONARDO FERNANDES; et al. Physico-Chemical Characterization and Biopharmaceutical Evaluation of Lipid-Poloxamer-Based Organogels for Curcumin Skin Delivery. FRONTIERS IN PHARMACOLOGY, v. 10, SEP 12 2019. (18/04036-3, 16/24456-1, 16/18045-9, 18/02482-6, 14/14457-5)

FEITOSA, RENATA CARVALHO; GERALDES, DANILO COSTA; BERALDO-DE-ARAUJO, VIVIANE LUCIA; RIBEIRO COSTA, JULIANA SOUZA; OLIVEIRA-NASCIMENTO, LAURA. Pharmacokinetic Aspects of Nanoparticle-in-Matrix Drug Delivery Systems for Oral/Buccal Delivery. FRONTIERS IN PHARMACOLOGY, v. 10, SEP 24 2019. (19/08281-5, 14/14457-5)

RODRIGUES DA SILVA, GUSTAVO HENRIQUE; DE MORAIS RIBEIRO, LIGIA NUNES; GUILHERME, VIVIANE APARECIDA; DE CASTRO, SIMONE RAMOS; BREITKREITZ, MARCIA CRISTINA; DE PAULA, ENEIDA. Bupivacaine (S75:R25) Loaded in Nanostructured Lipid Carriers: Factorial Design, HPLC Quantification Method and Physicochemical Stability Study. CURRENT DRUG DELIVERY, v. 15, n. 3, p. 388-396, 2018. (14/14457-5)

SAIA CEREDA, CINTIA MARIA; MECATTI, DANIEL SEBBE; BOAVA PAPINI, JULIANA ZAMPOLI; BUENO, DIEGO VALERIO; FRANZ-MONTAN, MICHELLE; ROCHA, THALITA; PEDRAZZOLI JUNIOR, JOSE; DE PAULA, ENEIDA; DE ARAUJO, DANIELE RIBEIRO; GRILLO, RENATO; et al. Bupivacaine in alginate and chitosan nanoparticles: an in vivo evaluation of efficacy, pharmacokinetics, and local toxicity. JOURNAL OF PAIN RESEARCH, v. 11, p. 683-691, 2018. (14/14457-5)

BERALDO-DE-ARAUJO, VIVIANE LUCIA; BERALDO-DE-ARAUJO, ANDERSON; RIBEIRO COSTA, JULIANA SOUZA; MARTINS PELEGRINE, ANA CAROLINA; MORAES RIBEIRO, LIGIA NUNES; DE PAULA, ENEIDA; OLIVEIRA-NASCIMENTO, LAURA. Excipient-excipient interactions in the development of nanocarriers: an innovative statistical approach for formulation decisions. SCIENTIFIC REPORTS, v. 9, JUL 24 2019. (14/14457-5)

RENNO, CAROLINA C.; PAPINI, JULIANA Z. B.; SAIA CEREDA, CINTIA MARIA; MARTINEZ, ELIZABETH; MONTALLI, VICTOR ANGELO; DE PAULA, ENEIDA; PEDRAZZOLI JUNIOR, JOSE; CALAFATTI, SILVANA APARECIDA; TOFOLI, GIOVANA RADOMILLE. Preclinical Evaluation of Ropivacaine in 2 Liposomal Modified Systems. ANESTHESIA AND ANALGESIA, v. 129, n. 2, p. 387-396, AUG 2019. (14/14457-5)

GUILHERME, VIVIANE A.; RIBEIRO, LIGIA N. M.; ALCANTARA, ANA C. S.; CASTRO, SIMONE R.; RODRIGUES DA SILVA, GUSTAVO H.; DA SILVA, CAMILA GONCALVES; BREITKREITZ, MARCIA C.; CLEMENTE-NAPIMOGA, JULIANA; MACEDO, CRISTINA G.; ABDALLA, HENRIQUE B.; et al. Improved efficacy of naproxen-loaded NLC for temporomandibular joint administration. SCIENTIFIC REPORTS, v. 9, AUG 1 2019. (13/10766-0, 14/14457-5)

DE ARAUJO, DANIELE RIBEIRO; DE MORAIS RIBEIRO, LIGIA NUNES; DE PAULA, ENEIDA. Lipid-based carriers for the delivery of local anesthetics. Expert Opinion on Drug Delivery, v. 16, n. 7, JUN 2019. (14/14457-5, 14/25372-0)

NASCIMENTO, M. H. M.; FRANCO, M. K. K. D.; YOKAICHYIA, F.; DE PAULA, E.; LOMBELLO, C. B.; DE ARAUJO, D. R.. Hyaluronic acid in Pluronic F-127/F-108 hydrogels for postoperative pain in arthroplasties: Influence on physico-chemical properties and structural requirements for sustained drug-release. International Journal of Biological Macromolecules, v. 111, p. 1245-1254, MAY 2018. (14/26200-9, 14/14457-5, 15/14763-1)

OLIVEIRA, JULIANA DAMASCENO; DE MORAIS RIBEIRO, LIGIA NUNES; RODRIGUES DA SILVA, GUSTAVO HENRIQUE; CASADEI, BRUNA RENATA; COUTO, VERONICA MUNIZ; MARTINEZ, ELIZABETH FERREIRA; DE PAULA, ENEIDA. Sustained Release from Ionic-Gradient Liposomes Significantly Decreases ETIDOCAINE Cytotoxicity. PHARMACEUTICAL RESEARCH, v. 35, n. 12, DEC 2018. (14/14457-5)

DA SILVA, GUSTAVO H. RODRIGUES; GERONIMO, GABRIELA; GARCIA-LOPEZ, JUAN P.; RIBEIRO, LIGIA N. M.; DE MOURA, LUDMILLA D.; BREITKREITZ, MARCIA C.; FEIJOO, CARMEN G.; DE PAULA, ENEIDA. Articaine in functional NLC show improved anesthesia and anti-inflammatory activity in zebrafish. SCIENTIFIC REPORTS, v. 10, n. 1, NOV 12 2020. (17/15174-5, 14/14457-5)

BEZAMAT, JULIANA M.; YOKAICHIYA, FABIANO; DIAS FRANCO, MARGARETH K. K.; CASTRO, SIMONE R.; DE PAULA, ENEIDA; CABECA, LUIS F.. Complexation of the local anesthetic pramoxine with hydroxypropyl-beta-cyclodextrin can improve its bioavailability. JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY, v. 55, FEB 2020. (14/14457-5)

DE LIMA, FERNANDO FREITAS; DA SILVA, BIANCA BRANDAO; OLIVEIRA, JULIANA DAMASCENO; DE MOURA, LUDMILLA DAVID; DA SILVA, GUSTAVO HENRIQUE RODRIGUES; FERNANDES, PRISCILA CORDEIRO LIMA; SOUZA, ROOSEVELT ISAIAS CARVALHO; DOS SANTOS, ARIANY CARVALHO; DE PAULA, ENEIDA. Prolonged anesthesia and decreased toxicity of enantiomeric-excess bupivacaine loaded in ionic gradient liposomes. International Journal of Pharmaceutics, v. 606, SEP 5 2021. (18/12121-0, 14/14457-5)

MONTEIRO DO NASCIMENTO, MONICA HELENA; AMBROSIO, FELIPE NOGUEIRA; FERRARAZ, DEBORA CARAJILIASCOV; WINDISCH-NETO, HERMANN; QUEROBINO, SAMYR MACHADO; NASCIMENTO-SALES, MICHELLE; ALBERTO-SILVA, CARLOS; CHRISTOFFOLETE, MARCELO AUGUSTO; FRANCO, MARGARETH K. K. D.; KENT, BEN; et al. Sulforaphane-loaded hyaluronic acid-poloxamer hybrid hydrogel enhances cartilage protection in osteoarthritis models. Materials Science & Engineering C-Materials for Biological Applications, v. 128, SEP 2021. (19/20303-4, 14/14457-5, 15/14763-1)

NASCIMENTO VIEIRA, ANA LAIS; FRANZ-MONTAN, MICHELLE; CABECA, LUIS FERNANDO; DE PAULA, ENEIDA. Anaesthetic benefits of a ternary drug delivery system (Ropivacaine-in-Cyclodextrin-in-Liposomes): in-vitro and in-vivo evaluation. Journal of Pharmacy and Pharmacology, v. 72, n. 3, DEC 2019. (14/14457-5)

MUNIZ, BRUNO VILELA; BARATELLI, DIEGO; DI CARLA, STEPHANY; SERPE, LUCIANO; DA SILVA, CAMILA BATISTA; GUILHERME, VIVIANE APARECIDA; DE MORAIS RIBEIRO, LIGIA NUNES; SAIA CEREDA, CINTIA MARIA; DE PAULA, ENEIDA; VOLPATO, MARIA CRISTINA; et al. Hybrid Hydrogel Composed of Polymeric Nanocapsules Co-Loading Lidocaine and Prilocaine for Topical Intraoral Anesthesia. SCIENTIFIC REPORTS, v. 8, DEC 19 2018. (12/06974-4, 13/22326-5, 14/14457-5)

VIGATO, ARYANE ALVES; QUEROBINO, SAMYR MACHADO; DE FARIA, NAIALLY CARDOSO; PINHEIRO DE FREITAS, ANDREA CAROLINA; LEONARDI, GISLAINE RICCI; DE PAULA, ENEIDA; SAIA CEREDA, CINTIA MARIA; TOFOLI, GIOVANA RADOMILLE; DE ARAUJO, DANIELE RIBEIRO. Synthesis and characterization of nanostructured lipid-poloxamer organogels for enhanced skin local anesthesia. European Journal of Pharmaceutical Sciences, v. 128, p. 270-278, FEB 1 2019. (18/02482-6, 14/14457-5, 18/04036-3)

MARTINS, PAULA; MACHADO, DAISY; THEIZEN, THAIS HOLTZ; OLIVEIRA GUARNIERI, JOAO PAULO; BERNARDES, BRUNO GAIA; GOMIDE, GABRIEL PICCIRILLO; FINZI CORAT, MARCUS ALEXANDRE; ABBEHAUSEN, CAMILLA; PROENCA MODENA, JOSE LUIZ; ODIR RODRIGUES MELO, CARLOS FERNANDO; et al. Outer Membrane Vesicles from Neisseria Meningitidis (Proteossome) Used for Nanostructured Zika Virus Vaccine Production. SCIENTIFIC REPORTS, v. 8, MAY 29 2018. (16/17066-2, 17/12719-0, 14/14457-5)

BARBOSA, RAQUEL DE M.; RIBEIRO, LIGIA N. M.; CASADEI, BRUNA R.; DA SILVA, CAMILA M. G.; QUEIROZ, VIVIANE A.; DURAN, NELSON; DE ARAUJO, DANIELE R.; SEVERINO, PATRICIA; DE PAULA, ENEIDA. Solid Lipid Nanoparticles for Dibucaine Sustained Release. PHARMACEUTICS, v. 10, n. 4, DEC 2018. (14/14457-5)

FRANZ-MONTAN, MICHELLE; DE MORAIS RIBEIRO, LIGIA NUNES; VOLPATO, MARIA CRISTINA; SAIA CEREDA, CINTIA MARIA; GROPPO, FRANCISCO CARLOS; TOFOLI, GIOVANA RANDOMILLE; DE ARAUJO, DANIELE RIBEIRO; SANTI, PATRIZIA; PADULA, CRISTINA; DE PAULA, ENEIDA. Recent advances and perspectives in topical oral anesthesia. Expert Opinion on Drug Delivery, v. 14, n. 5, p. 673-684, MAY 2017. (12/06974-4, 14/14457-5)

PRADO, ANDRESSA R.; YOKAICHIYA, FABIANO; KOBAYASHI DIAS FRANCO, MARGARETH KAZUYO; GONCALVES DA SILVA, CAMILA MORAIS; OLIVEIRA-NASCIMENTO, LAURA; FRANZ-MONTAN, MICHELLE; VOLPATO, MARIA C.; CABECA, LUIS F.; DE PAULA, ENEIDA. Complexation of oxethazaine with 2-hydroxypropyl--cyclodextrin: increased drug solubility, decreased cytotoxicity and analgesia at inflamed tissues. Journal of Pharmacy and Pharmacology, v. 69, n. 6, p. 652-662, JUN 2017. (14/14457-5)

RODRIGUES DA SILVA, GUSTAVO H.; RIBEIRO, LIGIA N. M.; MITSUTAKE, HERY; GUILHERME, VIVIANE A.; CASTRO, SIMONE R.; POPPI, RONEI J.; BREITKREITZ, MARCIA C.; DE PAULA, ENEIDA. Optimised NLC: a nanotechnological approach to improve the anaesthetic effect of bupivacaine. International Journal of Pharmaceutics, v. 529, n. 1-2, p. 253-263, AUG 30 2017. (14/14457-5)

AKKARI, ALESSANDRA C. S.; BOAVA PAPINI, JULIANA Z.; GARCIA, GABRIELLA K.; DIAS FRANCO, MARGARETH K. K.; CAVALCANTI, LEIDE P.; GASPERINI, ANTONIO; ALKSCHBIRS, MELISSA INGER; YOKAICHYIA, FABIANO; DE PAULA, ENEIDA; TOFOLI, GIOVANA R.; et al. Poloxamer 407/188 binary thermosensitive hydrogels as delivery systems for infiltrative local anesthesia: Physico-chemical characterization and pharmacological evaluation. Materials Science & Engineering C-Materials for Biological Applications, v. 68, p. 299-307, NOV 1 2016. (14/26200-9, 14/14457-5)

FRANZ-MONTAN, MICHELLE; SERPE, LUCIANO; MAIA MARTINELLI, CLAUDIA CRISTINA; DA SILVA, CAMILA BATISTA; DOS SANTOS, CLEITON PITA; NOVAES, PEDRO DUARTE; VOLPATO, MARIA CRISTINA; DE PAULA, ENEIDA; VIANNA LOPEZ, RENATA FONSECA; GROPPO, FRANCISCO CARLOS. Evaluation of different pig oral mucosa sites as permeability barrier models for drug permeation studies. European Journal of Pharmaceutical Sciences, v. 81, p. 52-59, JAN 1 2016. (11/23475-9, 12/06974-4, 11/18113-0, 14/14457-5)

SEPULVEDA, ANDERSON F.; KUMPGDEE-VOLLRATH, MONT; FRANCO, MARGARETH K. K. D.; YOKAICHIYA, FABIANO; DE ARAUJO, DANIELE R.. Supramolecular structure organization and rheological properties modulate the performance of hyaluronic acid-loaded thermosensitive hydrogels as drug-delivery systems. Journal of Colloid and Interface Science, v. 630, p. 13-pg., 2023-01-15. (14/14457-5, 19/20303-4)

CASTRO, SIMONE R.; RIBEIRO, LIGIA N. M.; BREITKREITZ, MARCIA C.; GUILHERME, VIVIANE A.; RODRIGUES DA SILVA, GUSTAVO H.; MITSUTAKE, HERY; ALCANTARA, ANA C. S.; YOKAICHIYA, FABIANO; FRANCO, MARGARETH K. K. D.; CLEMENS, DANIEL; et al. A pre-formulation study of tetracaine loaded in optimized nanostructured lipid carriers. SCIENTIFIC REPORTS, v. 11, n. 1, NOV 2 2021. (14/14457-5, 14/25372-0)

CALIXTO, GIOVANA MARIA FIORAMONTI; MUNIZ, BRUNO VILELA; CASTRO, SIMONE R.; DE ARAUJO, JAIZA SAMARA MACENA; AMORIM, KLINGER DE SOUZA; RIBEIRO, LIGIA N. M.; FERREIRA, LUIZ EDUARDO NUNES; DE ARAUJO, DANIELE RIBEIRO; DE PAULA, ENEIDA; FRANZ-MONTAN, MICHELLE. Mucoadhesive, Thermoreversible Hydrogel, Containing Tetracaine-Loaded Nanostructured Lipid Carriers for Topical, Intranasal Needle-Free Anesthesia. PHARMACEUTICS, v. 13, n. 11, NOV 2021. (18/25920-9, 19/07245-5, 14/14457-5)

MANTOVANI, RAPHAELA A.; XAVIER, ANA AUGUSTA O.; TAVARES, GUILHERME M.; MERCADANTE, ADRIANA Z.. Lutein bioaccessibility in casein-stabilized emulsions is influenced by the free to acylated carotenoid ratio, but not by the casein aggregation state. Food Research International, v. 161, p. 15-pg., 2022-08-27. (14/14457-5, 17/09214-4, 17/26237-8, 13/07914-8, 18/23752-1)

COUTO, V. M.; CASADEI, B. R.; RODRIGUES DA SILVA, G. H.; RISKE, K. A.; OLIVEIRA-NASCIMENTO, L.; DE PAULA, E.. Capsaicin and local anesthetics interaction with model membranes. EUROPEAN BIOPHYSICS JOURNAL WITH BIOPHYSICS LETTERS, v. 46, p. 1-pg., 2017-07-01. (15/09948-2, 14/14457-5, 15/11804-9)

Filed patent(s) as a result of this research project