24 results on '"Carolina Morales Moraes"'
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2. Validação de metodologia analítica por cromatografia líquida de alta eficiência para quantificação de bupivacaína (S75-R25) em nanoesferas de poli(lactídeo-co-glicolídeo) Validation of analytical methodology by HPLC for quantification of bupivacaine (S75-R25) in poli-lactide-co-glicolide nanospheres
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Carolina Morales Moraes, Eneida de Paula, André Henrique Rosa, and Leonardo Fernandes Fraceto
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bupivacaine ,PLGA nanospheres ,HPLC ,Chemistry ,QD1-999 - Abstract
Bupivacaine (S75-R25, NovaBupi®) is an amide type local anesthetic widely used. The present work consists of the development and validation of analytical methodology for evaluation of NovaBupi® content in the poly-lactide-co-glycolide nanospheres (PLGA-NS) by high performance liquid chromatography. The separation was made using the reversed-phase column LC-18, acetonitrile/phosphate buffer 85:15 v/v as mobile phase and detection at 220 nm. The results obtained show that the analytical methodology is accurate, reproducible, robust and linear over the concentration range 10-220.0 g/mL of NovaBupi®. The method was applied to determine the encapsulation efficiency and evaluate the release profile of NovaBupi®, showing good results.
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- 2008
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3. Caracterização do complexo de inclusão ropivacaína: beta-ciclodextrina
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Leonardo Fernandes Fraceto, Marcos Moisés Gonçalves, Carolina Morales Moraes, Daniele Ribeiro de Araújo, Luciana Zanella, Eneida de Paula, and Thelma de Aguiar Pertinhez
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ropivacaine ,cyclodextrin ,NMR ,Chemistry ,QD1-999 - Abstract
Characteriza of the inclusion complex ropivacaine: beta-cyclodextrin. Ropivacaine (RVC) is a widely used local anesthetic. The complexation of RVC with beta-cyclodextrin (beta-CD) is of great interest for the development of more efficient local anesthetic formulations. The present work focuses on the characterization of the RVC:beta-CD complex by nuclear magnetic resonance (NMR). The stoichiometry of the complex is 1:2 RVC:beta-CD. DOSY-NMR shows that the association constant is 55.5 M-1. Longitudinal relaxation time results show that RVC changes its mobility in the presence of beta-CD. This study is focused on the physicochemical characterization of inclusion complexes that are potentials options for pain treatment.
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- 2007
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4. Preparação e caracterização físico-química de complexos de inclusão entre anestésicos locais e hidroxipropil-beta-ciclodextrina Preperetion and physico-chemical characterization of inclusion complexes between local anesthetics and hydroxypropyl-b-cyclodextrin
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Carolina Morales Moraes, Priscila Abrami, Marcos Moisés Gonçalves, Newton Andréo Filho, Sérgio Antonio Fernandes, Eneida de Paula, and Leonardo Fernandes Fraceto
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S(-) Bupivacaine ,lidocaine ,cyclodextrin ,Chemistry ,QD1-999 - Abstract
S(-) Bupivacaine (S(-)BVC) and Lidocaine (LDC) are widely used local anesthetics (LA). Hydroxypropyl beta-cyclodextrin (HP-beta-CD) is used as a drug-carrier system. The aim of this work was to characterize inclusion complexes between LA and HP-beta-CD. The affinity constants determined at different pHs show favourable complexation. The release kinetics experiments showed that S(-)BVC and LDC changed the released profiles in the presence of HP-beta-CD. Nuclear magnetic resonance experiments gave information about the interaction between LA and the cyclodextrin cavity. This study focused on the physicochemical characterization of drug-delivery formulations that come out as potentially new therapeutic options for pain treatment.
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- 2007
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5. Mistura com excesso enantiomérico de 50% (S75-R25) de bupivacaína complexada com ciclodextrinas e anestesia por via subaracnóidea em ratos Mezcla con exceso enantiomérico de 50% (S75-R25) de bupivacaina con complejo de ciclodextrinas y anestesia por vía subaracnoidea en ratones Complexation of 50% enantiomeric excess (S75-R25) bupivacaine with cyclodextrins and spinal block anesthesia in rats
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Daniele Ribeiro de Araujo, Angélica de Fátima de Assunção Braga, Carolina Morales Moraes, Leonardo Fernandes Fraceto, and Eneida de Paula
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ANESTÉSICOS, Local ,ANIMAIS ,ANESTHETICS, Local ,ANIMALS ,Anesthesiology ,RD78.3-87.3 - Abstract
JUSTIFICATIVA E OBJETIVOS: Com a finalidade de prolongar a duração de ação e reduzir a toxicidade sistêmica, têm-se desenvolvido formulações de anestésicos locais (AL) complexados com ciclodextrinas (CD). Este estudo realizou a caracterização físico-química e avaliou, em ratos, os efeitos dos complexos de inclusão de bupivacaína racêmica (S50-R50) e da mistura com excesso enantiomérico de 50% (S75-R25) de bupivacaína com hidroxipropil-betaciclodextrina (HP-beta-CD), comparando-os com as soluções atualmente utilizadas na clínica. MÉTODO: Os complexos de inclusão de S75-R25 em HP-beta-CD (razão molar 1:1) foram caracterizados por estudos de solubilidade de fases variando-se as concentrações de HP-beta-CD e a temperatura. Determinaram-se as constantes de afinidade (K) pela HP-beta-CD e os parâmetros termodinâmicos para a complexação. Os bloqueios motor e sensitivo foram avaliados, por meio da administração subaracnóidea das formulações na concentração clínica de 0,5%. RESULTADOS: A formação de complexos de inclusão foi observada pelo aumento da solubilidade aquosa do AL sob diferentes temperaturas e concentrações de HP-beta-CD. Os testes in vivo mostraram que S50-R50HP-beta-CD e S75-R25HP-beta-CD reduziram a latência (p < 0,001) sem alterar o tempo de recuperação do bloqueio motor, tempo para efeito máximo e efeito total dos fármacos. Além disso, ambas as formulações aumentaram a intensidade (1,5 vez, p < 0,001) e prolongaram a duração da analgesia, com relação aos fármacos livres. CONCLUSÕES: Os complexos S50-R50HP-beta-CD e S75-R25HP-beta-CD potencializaram o bloqueio nervoso diferencial, podendo ser utilizados para reduzir a freqüência de administrações ou a dose de AL para indução de um mesmo efeito. A formulação contendo a mistura com excesso enantiomérico de 50% (S75-R25) de bupivacaína mostrou-se interessante no desenvolvimento de formulações seguras e úteis para o tratamento da dor aguda no período pós-operatório.JUSTIFICATIVA Y OBJETIVOS: Con la finalidad de prolongar la duración de la acción y reducir la toxicidad sistémica, se han desarrollado formulaciones de AL con complejo de ciclodextrinas (CD). Ese estudio realizó la caracterización físico-química y evaluó en ratones, los efectos de los complejos de inclusión de bupivacaína racémica (S50-R50) y de la mezcla con exceso enantiomérico de 50% (S75-R25) de bupivacaína con hidroxipropil-betaciclodextrina (HP-beta-CD), comparándolos con las soluciones actualmente utilizadas en la clínica. MÉTODO: Los complejos de inclusión de S75-R25 en HP-beta-CD (razón molar 1:1) fueron caracterizados por estudios de solubilidad de fases variando las concentraciones de HP-beta-CD y la temperatura. Fueron determinadas las constantes de afinidad (K) por la HP-beta-CD y los parámetros termodinámicos para los complejos. Los bloqueos motor y sensitivo fueron evaluados en ratones, a través de la administración subaracnoidea de las formulaciones en la concentración clínica de 0,5%. RESULTADOS: La formación de complejos de inclusión se observó a través del aumento de la solubilidad acuosa del AL bajo diferentes temperaturas y concentraciones de HP-beta-CD. Las pruebas in vivo mostraron que S50-R50HP-beta-CD y S75-R25HP-beta-CD redujeron la latencia (p < 0,001) sin alterar el tiempo de recuperación del bloqueo motor, tiempo para efecto máximo y efecto total de los fármacos. Además, ambas formulaciones aumentaron la intensidad (1,5 veces, p < 0,001) y prolongaron la duración de la analgesia, con relación a los fármacos libres. CONCLUSIONES: Los complejos, S50-R50HP-beta-CD y S75-R25HP-beta-CD, potenciaron el bloqueo nervioso diferencial, pudiendo ser utilizados para reducir la frecuencia de administraciones o la dosis de AL para inducción de un mismo efecto. La formulación conteniendo la mezcla con exceso enantiomérico de 50% (S75-R25) de bupivacaina fue interesante en el desarrollo de formulaciones seguras y útiles para el tratamiento del dolor agudo en el período postoperatorio.BACKGROUND AND OBJECTIVES: In order to prolong the action and reduce systemic toxicity, formulations of local anesthetic (LA) complexed with cyclodextrins (CD) have been developed. This study determined the physical-chemical characterization and evaluated the effects of inclusion complexes of racemic bupivacaine (S50-R50) and 50% enantiomeric excess (S75-R25) bupivacaine with hydroxypropil-beta-cyclodextrin (HP-beta-CD) in rats, and comparing them with the solutions currently used in the clinical practice. METHODS: Inclusion complexation of S75-R25 with HP-beta-CD (equimolar ratio 1:1) was characterized by phase-solubility studies varying the concentrations of HP-beta-CD and the temperature. Affinity constants (K) for HP-beta-CD and the thermodynamic parameters for complexation were determined. Motor and sensitive anesthesias were evaluated through the subarachnoid administration of the formulations in the concentration of 0.5%. RESULTS: Inclusion complexation was observed through the increase in aqueous solubility of LA in different temperatures and concentrations of HP-beta-CD. The in vivo tests demonstrated that S50-R50HP-beta-CD and S75-R25HP-beta-CD reduced latency (p < 0.001) without changing the recovery time of the motor block, time for maximal effect, and total effect of the drugs. Besides, both formulations increased the intensity (1.5 times, p < 0.001) and prolonged the duration of analgesia compared to the free drugs. CONCLUSIONS: The complexes S50-R50HP-beta-CD and S75-R25HP-beta-CD potentiated the differential nervous block, and can be used to reduce the frequency of administration or the dose of the LA to induce the same effect. The formulation containing enantiomeric excess (S75-R25) bupivacaine showed to be interesting in the development of safer formulations, and useful for the treatment of acute pain in the postoperative period.
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- 2006
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6. Sufentanil–2‐Hydroxypropyl‐β‐Cyclodextrin Inclusion Complex for pain Treatment: Physicochemical, Cytotoxicity, and Pharmacological Evaluation
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Cristiane Volobuef, Angélica de Fátima de Assunção Braga, Margareth K.K.D. Franco, Lázaro Alessandro Soares Nunes, Daniele Ribeiro de Araujo, Giovana Radomille Tofoli, Eneida de Paula, Fabiano Yokaichiya, Leonardo Fernandes Fraceto, Carolina Morales Moraes, and Cíntia Maria Saia Cereda
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Male ,Erythrocytes ,Magnetic Resonance Spectroscopy ,Sufentanil ,Chemistry, Pharmaceutical ,Analgesic ,Pain ,Pharmaceutical Science ,Beta-Cyclodextrins ,Pharmacology ,Drug Delivery Systems ,X-Ray Diffraction ,Spectroscopy, Fourier Transform Infrared ,medicine ,Animals ,Humans ,Rats, Wistar ,Calorimetry, Differential Scanning ,Chemistry ,beta-Cyclodextrins ,Controlled release ,Binding constant ,2-Hydroxypropyl-beta-cyclodextrin ,Rats ,Opioid ,Toxicity ,Ex vivo ,medicine.drug - Abstract
Sufentanil (SUF) is a synthetic analgesic opioid widely used for the management of acute and chronic pain. This drug was complexed with 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) and the physicochemical characterization, in vitro/ex vivo toxicity assays, and pharmacological evaluation were performed. Differential scanning calorimetry, Fourier transform infrared spectroscopy (FTIR) analysis, and X-ray powder diffraction showed the formation and the morphology of the complex. Nuclear magnetic resonance afforded data regarding inclusion complex stoichiometry (1:1) with an association binding constant (K(a)) value of 515.2 ± 1.2 M(-1) between SUF and HP-β-CD. Complexation with HP-β-CD protected SUF from light exposure and increased its photostability. Release kinetics revealed a decrease in SUF release rate (K(rel) = 7.05 ± 0.52 and 5.61 ± 0.39 min(-1/2) for SUF-HP-β-CD and SUF, respectively) and reduced hemolytic or myotoxic effects after complexation. Time course of tail-flick test showed that the duration of analgesia induced by SUF (150.0 ± 34.6 min) was significantly increased (p0.001) after complexation with HP-β-CD (355.7 ± 47.2 min) when injected at the same dose (1 μg kg(-1)), prolonging the duration of analgesia after intramuscular administration and representing an alternative on the development of effective and safe drug-delivery system for opioid analgesics.
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- 2012
7. Benzocaine-Loaded Polymeric Nanocapsules: Study of the Anesthetic Activities
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André Henrique Rosa, Leonardo Fernandes Fraceto, Renato Grillo, Eneida de Paula, Nathalie Ferreira Silva de Melo, Daniele Ribeiro de Araujo, Angélica Prado de Matos, and Carolina Morales Moraes
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Male ,Benzocaine ,Polyesters ,Dispersity ,Pharmaceutical Science ,Nanocapsules ,Mice ,Polylactic Acid-Polyglycolic Acid Copolymer ,Polymer chemistry ,medicine ,Animals ,Lactic Acid ,Anesthetics, Local ,Particle Size ,chemistry.chemical_classification ,Polymer ,Sciatic Nerve ,Controlled release ,Biodegradable polymer ,chemistry ,Anesthetic ,Particle size ,Polyglycolic Acid ,medicine.drug ,Nuclear chemistry - Abstract
This paper describes a comparison of different polymeric nanocapsules (NCs) prepared with the polymers poly(D,L-lactide-co-glycolide), poly(L-lactide) (PLA), and poly(ε-caprolactone) and used as carrier systems for the local anesthetic (LA) benzocaine (BZC). The systems were characterized and their anesthetic activities investigated. The results showed particle size distributions with polydispersity indices below 0.135, average diameters up to 120 nm, zeta potentials up to -30 mV, and entrapment efficiencies around 70%. Formulations of BZC using the polymeric NCs presented slower release profiles, compared with that of free BZC. Slowest release (release constant, k = 0.0016 min(-1)) was obtained using the PLA NC system. Pharmacological evaluation showed that encapsulation of BZC in PLA NCs prolonged its anesthetic action. This new formulation could potentially be used in future applications involving the gradual release of local anesthetics (LAs).
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- 2012
8. Screening of Formulation Variables for the Preparation of Poly(ε-caprolactone) Nanocapsules Containing the Local Anesthetic Benzocaine
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André Henrique Rosa, Renato Grillo, Newton Luiz Dias Filho, Carolina Morales Moraes, Leonardo Fernandes Fraceto, Nathalie Ferreira Silva de Melo, Eneida de Paula, and Angélica Prado de Matos
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chemistry.chemical_classification ,Chromatography ,Materials science ,Aqueous solution ,Stereochemistry ,Biomedical Engineering ,Bioengineering ,General Chemistry ,Polymer ,Condensed Matter Physics ,Nanocapsules ,Benzocaine ,Colloid ,chemistry ,medicine ,Zeta potential ,General Materials Science ,Particle size ,Drug carrier ,medicine.drug - Abstract
In this work we describe the screening of four parameters in the preparation, by nanoprecipitation, of poly(epsilon-caprolactone) nanocapsules, used as a drug carrier system for the local anesthetic, benzocaine. A 2(4-1) factorial experimental design was used to study the influence of four different independent variables (polymer, oily phase, Span 60 and Tween 80) on nanocapsule characteristics (size, polydispersion index, zeta potential) and drug loading capability. Best results were obtained using an aqueous formulation comprising 100 mg of polymer, 200 mg of oily phase, 40 mg of Span 60 and 60 mg of Tween 80 in a final volume of 10 mL which produced a colloidal system with particle size of 188 nm, zeta potential -32 mV, polydispersion index 0.07, and benzocaine association efficiency > 87%. These findings open the way for future clinical studies using such formulations.
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- 2011
9. Benzocaine loaded biodegradable poly-(d,l-lactide-co-glycolide) nanocapsules: factorial design and characterization
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Angélica Prado de Matos, Eneida de Paula, Carolina Morales Moraes, André Henrique Rosa, and Leonardo Fernandes Fraceto
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Materials science ,Mechanical Engineering ,Dispersity ,Nanotechnology ,Factorial experiment ,Condensed Matter Physics ,Nanocapsules ,Benzocaine ,PLGA ,chemistry.chemical_compound ,Chemical engineering ,chemistry ,Mechanics of Materials ,Drug delivery ,Zeta potential ,medicine ,General Materials Science ,Particle size ,medicine.drug - Abstract
Local anesthetics are able to induce pain relief since they bind to the sodium channel of excitable membranes, blocking the influx of sodium ions and the propagation of the nervous impulse. Benzocaine (BZC) is a local anesthetic that presents limited application in topical formulations due to its low water-solubility. This study aimed to develop polymeric nanocapsules as a drug delivery system for the local anesthetic benzocaine (BZC). To do so, BZC loaded poly( d,l -lactide-co-glycolide) (PLGA) nanocapsules were prepared using the nanoprecipitation method and were characterized. The factorial experimental design was used to study the influence of four different independent variables on response to nanocapsules drug loading. The physical characteristics of PLGA nanocapsules were evaluated by analyzing the particle size, the polydispersion index and the zeta potential, using a particle size analyzer. The results of the optimized formulation showed a size distribution with a polydispersity index of 0.12, an average diameter of 123 nm, zeta potential of −33.6 mV and a drug loading of more than 69%. The release profiles showed a significant difference in the release behavior for the pure drug in solution when compared with that containing benzocaine loaded PLGA nanocapsules. Thus, the prepared nanocapsules described here may be of clinical importance in both the processes of stabilization and delivery of benzocaine for pain treatment.
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- 2009
10. Encapsulation of Local Anesthetic Bupivacaine in Biodegradable Poly(DL-lactide-co-glycolide) Nanospheres: Factorial Design, Characterization and Cytotoxicity Studies
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Renata de Lima, Leonardo Fernandes Fraceto, Eneida de Paula, André Henrique Rosa, and Carolina Morales Moraes
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Bupivacaine ,Materials science ,Polymers and Plastics ,Local anesthetic ,medicine.drug_class ,Organic Chemistry ,Factorial experiment ,Condensed Matter Physics ,PLGA ,chemistry.chemical_compound ,chemistry ,Toxicity ,Drug delivery ,Materials Chemistry ,medicine ,Zeta potential ,Cytotoxicity ,medicine.drug ,Biomedical engineering - Abstract
Local anesthetic agents cause temporary blockade of nerve impulses productiong insensitivity to painful stimuli in the area supplied by that nerve. Bupivacaine (BVC) is an amide-type local anesthetic widely used in surgery and obstetrics for sustained peripheral and central nerve blockade. in this study, we prepared and characterized nanosphere formulations containing BVC. To achieve these goals, BVC loaded poly(DL-lactide-co-glycolide) (PLGA) nanospheres (NS) were prepared by nanopreciptation and characterized with regard to size distribution, drug loading and cytotoxicity assays. The 2 3-1 factorial experimental design was used to study the influence of three different independent variables on nanoparticle drug loading. BVC was assayed by HPLC, the particle size and zeta potential were determined by dynamic light scattering. BVC was determined using a combined ultrafiltration-centrifugation technique. The results of optimized formulations showed a narrow size distribution with a polydispersivity of 0.05%, an average diameter of 236.7 ± 2.6 nm and the zeta potential -2.93 ± 1,10 mV. In toxicity studies with fibroblast 3T3 cells, BVC loaded-PLGA-NS increased cell viability, in comparison with the effect produced by free BVC. In this way, BVC-loaded PLGA-NS decreased BVC toxicity. The development of BVC formulations in carriers such as nanospheres could offer the possibility of controlling drug delivery in biological systems, prolonging the anesthetic effect and reducing toxicity.
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- 2009
11. Physico-chemical characterization of inclusion complex between hydroxymethylnitrofurazone and hydroxypropyl-beta-cyclodextrin
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Carla Maria de Souza Menezes, Elizabeth Igne Ferreira, Gustavo Henrique Goulart Trossini, Leonardo Fernandes Fraceto, Nathalie Ferreira Silva de Melo, Carolina Morales Moraes, Charles Lima Brito, Renato Grillo, Universidade Estadual Paulista (Unesp), Universidade de São Paulo (USP), and Universidade Estadual de Campinas (UNICAMP)
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cyclodextrin ,Stereochemistry ,Chemistry ,hydroxymethylnitrofurazone ,General Chemistry ,Prodrug ,Solubility ,inclusion complex ,Nuclear chemistry - Abstract
Submitted by Guilherme Lemeszenski (guilherme@nead.unesp.br) on 2013-08-22T18:48:41Z No. of bitstreams: 1 S0100-40422008000200019.pdf: 357548 bytes, checksum: 6552184bfe69044965288daec0b830ac (MD5) Made available in DSpace on 2013-08-22T18:48:41Z (GMT). No. of bitstreams: 1 S0100-40422008000200019.pdf: 357548 bytes, checksum: 6552184bfe69044965288daec0b830ac (MD5) Previous issue date: 2008-01-01 Made available in DSpace on 2013-09-30T19:38:43Z (GMT). No. of bitstreams: 2 S0100-40422008000200019.pdf: 357548 bytes, checksum: 6552184bfe69044965288daec0b830ac (MD5) S0100-40422008000200019.pdf.txt: 32801 bytes, checksum: 1d3b50bb0b94329399b05319e8232b0e (MD5) Previous issue date: 2008-01-01 Submitted by Vitor Silverio Rodrigues (vitorsrodrigues@reitoria.unesp.br) on 2014-05-20T13:12:10Z No. of bitstreams: 2 S0100-40422008000200019.pdf: 357548 bytes, checksum: 6552184bfe69044965288daec0b830ac (MD5) S0100-40422008000200019.pdf.txt: 32801 bytes, checksum: 1d3b50bb0b94329399b05319e8232b0e (MD5) Made available in DSpace on 2014-05-20T13:12:10Z (GMT). No. of bitstreams: 2 S0100-40422008000200019.pdf: 357548 bytes, checksum: 6552184bfe69044965288daec0b830ac (MD5) S0100-40422008000200019.pdf.txt: 32801 bytes, checksum: 1d3b50bb0b94329399b05319e8232b0e (MD5) Previous issue date: 2008-01-01 Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Hydroxymethylnitrofurazone (NFOH) is a prodrug that is active against Trypanosoma cruzi. It however presents low solubility and high toxicity. Hydroxypropyl-beta-cyclodextrin (HP-beta-CD) can be used as a drug-delivery system for NFOH modifying its physico-chemical properties. The aim of this work is to characterize the inclusion complex between NFOH and HP-beta-CD. The rate of NFOH release decreases after complexation and thermodynamic parameters from the solubility isotherm studies revealed that a stable complex is formed (deltaGº= 1.7 kJ/mol). This study focuses on the physico-chemical characterization of a drug-delivery formulation that comes out as a potentially new therapeutic option for Chagas disease treatment. Universidade Estadual Paulista Júlio de Mesquita Filho Departamento de Engenharia Ambiental Universidade de São Paulo Faculdade de Ciências Farmacêuticas Universidade Estadual de Campinas Instituto de Biologia Departamento de Bioquímica Universidade Estadual Paulista Júlio de Mesquita Filho Departamento de Engenharia Ambiental
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- 2008
12. Hydroxymethylnitrofurazone:Dimethyl-β-cyclodextrin Inclusion Complex: A Physical–Chemistry Characterization
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Carla Maria de Souza Menezes, Leonardo Fernandes Fraceto, Elizabeth Igne Ferreira, Carolina Morales Moraes, Nathalie Ferreira Silva de Melo, Renato Grillo, André Henrique Rosa, and José Arnaldo Frutuoso Roveda
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chemistry.chemical_classification ,Cyclodextrin ,medicine.diagnostic_test ,Chemistry ,Kinetics ,Biophysics ,Cell Biology ,Pharmaceutical formulation ,Atomic and Molecular Physics, and Optics ,Absorbance ,Spectrophotometry ,medicine ,Physical chemistry ,Molecule ,Solubility ,Drug carrier ,Molecular Biology ,Research Paper - Abstract
Hydroxymethylnitrofurazone (NFOH) is active against Trypanosoma cruzi; however, its low solubility and high toxicity precludes its current use in treatment of parasitosis. Cyclodextrin can be used as a drug carrier system, as it is able to form inclusion (host-guest) complexes with a wide variety of organic (guest) molecules. Several reports have shown the interesting use of modified beta-cyclodextrins in pharmaceutical formulation, to improve the bioavailability of drugs and to decrease their toxicity. The aim of this work was to characterize inclusion complexes formed between NFOH and dimethyl-beta-cyclodextrin (DM-beta-CD) by complexation/release kinetics and solubility isotherm experiments using ultraviolet (UV)-visible spectrophotometry and by the measurement of the dynamics information obtained from T(1) relaxation times and diffusion (DOSY) experiments using nuclear magnetic resonance (NMR) spectroscopy. The complex was prepared at different NFOH and DM-beta-CD molar ratios. The UV-visible measurements were recorded in a spectrophotometer, and NMR experiments were recorded at 20 degrees C on a NMR spectrometer (Varian Inova) operating at 500 MHz. Longitudinal relaxation times were obtained by the conventional inversion-recovery method and the DOSY experiments were carried out using the BPPSTE sequence. The kinetics of complexation revealed that 30 h is enough for stabilization of the NFOH absorbance in presence of cyclodextrin. Solubility isotherm studies show a favorable complexation and increase in solubility when NFOH interacts with cyclodextrin. The analysis of the NMR-derived diffusion coefficients and T(1) relaxation times shows that in the presence of DM-beta-CD, NFOH decreases its mobility in solution, indicating that this antichagasic compound interacts with the cyclodextrin cavity. The release kinetics assays showed that NFOH changes its release profile when in the presence of cyclodextrin due to complexation. This study was focused on the physicochemical characterization of drug-delivery formulations that may serve as potentially new therapeutic options for the treatment of Chagas' disease.
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- 2007
13. Initial Development and Characterization of PLGA Nanospheres Containing Ropivacaine
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Leonardo Fernandes Fraceto, Eneida de Paula, Renata de Lima, André Henrique Rosa, Carolina Morales Moraes, and Angélica Prado de Matos
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chemistry.chemical_classification ,Original Paper ,Chemistry ,Ropivacaine ,Sodium ,Biophysics ,Nanoparticle ,chemistry.chemical_element ,Nanotechnology ,Cell Biology ,Polymer ,Atomic and Molecular Physics, and Optics ,PLGA ,chemistry.chemical_compound ,Drug delivery ,Zeta potential ,medicine ,Particle size ,Molecular Biology ,Nuclear chemistry ,medicine.drug - Abstract
Local anesthetics are able to induce pain relief by binding to the sodium channels of excitable membranes, blocking the influx of sodium ions and the propagation of the nervous impulse. Ropivacaine (RVC) is an amino amide, enantiomerically pure, local anesthetic largely used in surgical procedures, which present physico-chemical and therapeutic properties similar to those of bupivacaine but decreased toxicity and motor blockade. The present work focuses on the preparation and characterization of nanospheres containing RVC; 0.25% and 0.50% RVC were incorporated in poly(d,l-lactide-co-glycolide (PLGA) 50:50) nanospheres (PLGA-NS), prepared by the nanoprecipitation method. Characterization of the nanospheres was conducted through the measurement of pH, particle size, and zeta potential. The pH of the nanoparticle system with RVC was 6.58. The average diameters of the RVC-containing nanospheres was 162.7 +/- 1.5 nm, and their zeta potentials were negative, with values of about -10.81 +/- 1.16 mV, which promoted good stabilization of the particles in solution. The cytotoxicity experiments show that RVC-loaded PLGA-NS generate a less toxic formulation as compared with plain RVC. Since this polymer drug-delivery system can effectively generate an even less toxic RVC formulation, this study is fundamental due to its characterization of a potentially novel pharmaceutical form for the treatment of pain with RVC.
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- 2007
14. Preparação e caracterização físico-química de complexos de inclusão entre anestésicos locais e hidroxipropil-beta-ciclodextrina Preperetion and physico-chemical characterization of inclusion complexes between local anesthetics and hydroxypropyl-<FONT FACE=Symbol>b</font>-cyclodextrin
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Carolina Morales Moraes, Priscila Abrami, Marcos Moisés Gonçalves, Newton Andréo Filho, Sérgio Antonio Fernandes, Eneida de Paula, and Leonardo Fernandes Fraceto
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lcsh:Chemistry ,cyclodextrin ,lcsh:QD1-999 ,lidocaine ,S(-) Bupivacaine - Abstract
S(-) Bupivacaine (S(-)BVC) and Lidocaine (LDC) are widely used local anesthetics (LA). Hydroxypropyl beta-cyclodextrin (HP-beta-CD) is used as a drug-carrier system. The aim of this work was to characterize inclusion complexes between LA and HP-beta-CD. The affinity constants determined at different pHs show favourable complexation. The release kinetics experiments showed that S(-)BVC and LDC changed the released profiles in the presence of HP-beta-CD. Nuclear magnetic resonance experiments gave information about the interaction between LA and the cyclodextrin cavity. This study focused on the physicochemical characterization of drug-delivery formulations that come out as potentially new therapeutic options for pain treatment.
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- 2007
15. Study of the interaction between S(−) bupivacaine and 2-hydroxypropyl-β-cyclodextrin
- Author
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Angélica de Fátima de Assunção Braga, Carolina Morales Moraes, Eneida de Paula, Leonardo Fernandes Fraceto, and Priscila Abrami
- Subjects
Magnetic Resonance Spectroscopy ,Chemistry, Pharmaceutical ,Sodium ,Pharmaceutical Science ,chemistry.chemical_element ,Beta-Cyclodextrins ,High-performance liquid chromatography ,Inclusion compound ,Excipients ,chemistry.chemical_compound ,Phase (matter) ,Anesthetics, Local ,Solubility ,Chromatography, High Pressure Liquid ,Chromatography ,beta-Cyclodextrins ,Temperature ,Hydrogen-Ion Concentration ,Bupivacaine ,2-Hydroxypropyl-beta-cyclodextrin ,chemistry ,Stability constants of complexes ,Thermodynamics ,Stoichiometry ,Nuclear chemistry - Abstract
Local anesthetics are substances able to induce pain relief by binding to the sodium channel of excitable membranes, blocking the influx of sodium ions and the propagation of nervous impulses. S(--) bupivacaine (S(--) bvc) is an amide type local anesthetic widely used in surgery and obstetrics for sustained peripheral and central nerve blockade. The present work focuses on the characterization of an inclusion complex of S(--) bvc in 2-hydroxypropyl-beta-cyclodextrin (HP-beta-CD). The complexation with HP-beta-CD has been investigated using reversed-phase liquid chromatography and solubility isotherms. The retention behavior was analyzed on a reversed phase C18 column and the mobile phase used was acetonitrile-phosphate buffer pH 7.4 (10mM), (45/55, v/v), in which HP-beta-CD was incorporated as a mobile phase additive. The decrease in the retention times with increasing concentration of HP-beta-CD enables the determination of the complex apparent stability constants by HPLC as a function of temperature. The solubility isotherms were studied as a function of pH (7.4 and 10.5) and temperature. The pH study showed that S(--) bvc reaches a concentration at least 1.5 and 4.5 times higher (pH 7.4 and 10.5, respectively) than the one presented by the free drug in water. The calculated values for the apparent stability constant (K) are 13.1+/-2.8 and 95.4+/-11.8M(-1) for pH 7.4 and 10.5, respectively, thus indicating the formation of a stable complex. In addition, the study of the apparent stability constant by HPLC and solubility isotherm gives thermodynamics information about the interaction between S(--) bvc and HP-beta-CD. The application of the continuous variation method indicated the presence of a complex with 1:1 S(--) bvc:HP-beta-CD stoichiometry. This is an important study for the characterization of potential formulations to be used as therapeutic options for the treatment of pain.
- Published
- 2007
16. Characterization of lidocaine:hydroxypropyl-β-cyclodextrin inclusion complex
- Author
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Angélica de Fátima de Assunção Braga, Eneida de Paula, Carolina Morales Moraes, Michelle Georges Issa, Humberto Gomes Ferraz, Leonardo Fernandes Fraceto, Daniele Riberio de Araujo, and Priscila Abrami
- Subjects
Differential scanning calorimetry ,Chromatography ,Chemistry ,Uv absorption ,General Chemistry ,Condensed Matter Physics ,Thermal analysis ,Endothermic process ,High-performance liquid chromatography ,Biological sciences ,Hydroxypropyl β cyclodextrin ,Food Science - Abstract
An inclusion complex was prepared between the local anesthetic lidocaine (LDC) and hydroxypropyl-β-CD (HP-β-CD). The complex was characterized by thermal analysis (differential scanning calorimetry, DSC), UV absorption and high-pressure liquid chromatography (HPLC). DSC results were indicative of complexation, due to the loss of the characteristic endothermic peak of LDC (77 °C). Phase-solubility diagrams allowed the determination of the association constant between LDC and HP-β-CD (35.7 ± 4.7 M−1). The rate of LDC release decreased after complexation and thermodynamic parameters from the HPLC studies (ΔG° = −2.65 kJ/mol) revealed that a stable complex was formed.
- Published
- 2007
17. Screening of formulation variables for the preparation of poly(epsilon-caprolactone) nanocapsules containing the local anesthetic benzocaine
- Author
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Carolina Morales, Moraes, Angélica Prado, de Matos, Renato, Grillo, Nathalie F S, de Melo, Eneida, de Paula, Newton Luiz, Dias Filho, André Henrique, Rosa, and Leonardo Fernandes, Fraceto
- Subjects
Nanocapsules ,Surface Properties ,Benzocaine ,Drug Compounding ,Polyesters ,Materials Testing ,Combinatorial Chemistry Techniques - Abstract
In this work we describe the screening of four parameters in the preparation, by nanoprecipitation, of poly(epsilon-caprolactone) nanocapsules, used as a drug carrier system for the local anesthetic, benzocaine. A 2(4-1) factorial experimental design was used to study the influence of four different independent variables (polymer, oily phase, Span 60 and Tween 80) on nanocapsule characteristics (size, polydispersion index, zeta potential) and drug loading capability. Best results were obtained using an aqueous formulation comprising 100 mg of polymer, 200 mg of oily phase, 40 mg of Span 60 and 60 mg of Tween 80 in a final volume of 10 mL which produced a colloidal system with particle size of 188 nm, zeta potential -32 mV, polydispersion index 0.07, and benzocaine association efficiency87%. These findings open the way for future clinical studies using such formulations.
- Published
- 2011
18. Physicochemical stability of poly(lactide-co-glycolide) nanocapsules containing the local anesthetic Bupivacaine
- Author
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Eneida de Paula, André Henrique Rosa, Leonardo Fernandes Fraceto, Carolina Morales Moraes, Universidade Estadual de Campinas (UNICAMP), and Universidade Estadual Paulista (Unesp)
- Subjects
Bupivacaine ,Materials science ,Local anesthetic ,medicine.drug_class ,Dispersity ,bupivacaine ,PLGA ,physical-chemical stability ,Nanotechnology ,General Chemistry ,Nanocapsules ,chemistry.chemical_compound ,chemistry ,Chemical engineering ,In vivo ,medicine ,Zeta potential ,local anesthetic ,Drug carrier ,polymeric nanocapsules ,medicine.drug - Abstract
This paper describes the preparation of poly(DL-lactide-co-glicolide) (PLGA) nanocapsules as a drug carrier system for the local anesthetic bupivacaine. The system was characterized and its stability investigated. The results showed a size distribution with a polydispersity index of 0.12, an average diameter of 148 nm, a zeta potential of -43.5 mV and an entrapment efficiency of 75.8%. The physicochemical properties of polymeric nanocapsule suspensions (average diameter, polydispersity, zeta potential and drug association efficiency) were evaluated as a function of time to determine the formulation stability. The formulation did not display major changes in these properties over the time, and it was considered stable up to 120 days of storage at room temperature. The results reported here which refer to the initial characterization of these new formulations for the local anesthetic bupivacaine show a promising potential for future in vivo studies. Neste trabalho foi realizada a preparação de nanocápsulas de poli (DL-lactídeo-co-glicolídeo) (PLGA) como um sistema carreador para o anestésico local bupivacaína. A preparação foi caracterizada e sua estabilidade físico-química avaliada. Os resultados da caracterização mostram uma distribuição de tamanho com um índice de polidispersão de 0,12, um diâmetro médio de 148 nm, um potencial zeta de -43,5 mV e uma eficiência de associação da BVC nas nanocápsulas de 75,8%. As propriedades físico-químicas das suspensões (diâmetro hidrodinâmico, índice de polidispersão, potencial zeta e eficiência de associação do fármaco) contendo nanocápsulas poliméricas foram avaliadas em função do tempo a fim de determinar sua estabilidade. Nenhuma grande alteração foi observada em função tempo para as suspensões de nanocápsulas avaliadas, sendo consideradas estáveis por um período de armazenagem de 120 dias a temperatura ambiente. Os resultados aqui apresentados, os quais se referem ao estudo desta nova formulação para anestésico local bupivacaína mostram-se promissores para futuros estudos in vivo.
- Published
- 2010
19. Preparation, physicochemical characterization and stability evaluation of polymeric nanoparticles containing local anesthetics
- Author
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Carolina Morales Moraes, Fraceto, Leonardo Fernandes, Paula, Eneida de, 1963, Pessine, Francisco Benedito Teixeira, Duran Caballero, Nelson Eduardo, Melo, Patricia da Silva, Universidade Estadual de Campinas. Instituto de Biologia, Programa de Pós-Graduação em Biologia Funcional e Molecular, and UNIVERSIDADE ESTADUAL DE CAMPINAS
- Subjects
Anesthesia, local ,Anestesia local ,Nanocapsules ,Bupivacaina - Anestesia local ,Benzocaine ,Nanopartículas ,Nanoparticles ,Nanocápsulas ,Benzocaína ,Bupivacaine - Abstract
Orientadores: Leonardo Fernandes Fraceto, Eneida de Paula Dissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Biologia Resumo: As principais características desejáveis para um anestésico local incluem longa duração de ação e baixa toxicidade sistêmica. Uma alternativa que tem se mostrado capaz de promover estes efeitos desejáveis é a liberação sustentada de fármacos através da veiculação destes em sistemas carreadores, como as nanopartículas. Nanopartículas poliméricas são sistemas carreadores que apresentam diâmetro inferior a 1µm e são classificadas como nanoesferas ou nanocápsulas. As nanocápsulas são constituídas por um invólucro polimérico disposto ao redor de um núcleo, geralmente oleoso, enquanto as nanoesferas são formadas somente por uma matriz polimérica. Os estágios iniciais do desenvolvimento de novas formulações contendo nanocarreadores de fármacos envolvem a otimização das condições de preparo, caracterização físico-química, avaliação da estabilidade e determinação do perfil de liberação do fármaco carreado, sendo esta a proposta desse trabalho. A otimização de formulações de nanocápsulas: a) de poli(ácido-lático-coácido- glicólico) contendo o anestésico local benzocaína; b) de poli (ácido lático-coglicólico) contendo bupivacaína e de c) de poli (e-caprolactona) contendo benzocaína, foi alcançada a partir de um planejamento fatorial, onde as propriedades avaliadas foram diâmetro das partículas, polidispersão, potencial zeta e eficiência de associação do fármaco nas nanocápsulas, em função de variações nas concentrações de polímero, óleo e tensoativos. Propriedades físicoquímicas das suspensões de nanocápsulas (das partículas, polidispersão, potencial zeta e eficiência de associação do fármaco) poliméricas foram avaliadas em função do tempo, a fim de determinar a estabilidade das formulações. Nenhuma das formulações estudadas apresentou grandes alterações dessas propriedades em função do tempo, sendo consideradas estáveis por um período de até 120 dias de armazenamento em temperatura ambiente. Foram obtidas nanocápsulas poliméricas de diâmetro, polidispersão, potencial zeta, eficiência de associação, perfil de liberação in vitro e estabilidade adequadas para a finalidade e via de administração infiltrativa. Os resultados apresentados são referentes a estudos iniciais do desenvolvimento dessas novas formulações visando reduzir a toxicidade, aumentar a solubilidade de anestésicos locais e abrem perspectivas para estudos pré-clínicos e clínicos, uma vez que se mostraram promissores Abstract: Não informado Mestrado Bioquímica Mestre em Biologia Funcional e Molecular
- Published
- 2009
20. Validação de metodologia analítica por cromatografia líquida de alta eficiência para quantificação de bupivacaína (S75-R25) em nanoesferas de poli(lactídeo-co-glicolídeo)
- Author
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Leonardo Fernandes Fraceto, Eneida de Paula, Carolina Morales Moraes, André Henrique Rosa, Universidade Estadual de Campinas (UNICAMP), and Universidade Estadual Paulista (Unesp)
- Subjects
Amide type local anesthetic ,Chromatography ,PLGA nanospheres ,Chemistry ,Phosphate buffered saline ,Analytical chemistry ,bupivacaine ,General Chemistry ,HPLC ,High-performance liquid chromatography - Abstract
Submitted by Guilherme Lemeszenski (guilherme@nead.unesp.br) on 2013-08-22T18:48:45Z No. of bitstreams: 1 S0100-40422008000800040.pdf: 155853 bytes, checksum: d5986404858997cebff639bcc5ba6e22 (MD5) Made available in DSpace on 2013-08-22T18:48:45Z (GMT). No. of bitstreams: 1 S0100-40422008000800040.pdf: 155853 bytes, checksum: d5986404858997cebff639bcc5ba6e22 (MD5) Previous issue date: 2008-01-01 Made available in DSpace on 2013-09-30T19:38:47Z (GMT). No. of bitstreams: 2 S0100-40422008000800040.pdf: 155853 bytes, checksum: d5986404858997cebff639bcc5ba6e22 (MD5) S0100-40422008000800040.pdf.txt: 22859 bytes, checksum: 1ccd3d9efe937a9259f82c0422b81f96 (MD5) Previous issue date: 2008-01-01 Submitted by Vitor Silverio Rodrigues (vitorsrodrigues@reitoria.unesp.br) on 2014-05-20T15:10:24Z No. of bitstreams: 2 S0100-40422008000800040.pdf: 155853 bytes, checksum: d5986404858997cebff639bcc5ba6e22 (MD5) S0100-40422008000800040.pdf.txt: 22859 bytes, checksum: 1ccd3d9efe937a9259f82c0422b81f96 (MD5) Made available in DSpace on 2014-05-20T15:10:24Z (GMT). No. of bitstreams: 2 S0100-40422008000800040.pdf: 155853 bytes, checksum: d5986404858997cebff639bcc5ba6e22 (MD5) S0100-40422008000800040.pdf.txt: 22859 bytes, checksum: 1ccd3d9efe937a9259f82c0422b81f96 (MD5) Previous issue date: 2008-01-01 Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Bupivacaine (S75-R25, NovaBupi®) is an amide type local anesthetic widely used. The present work consists of the development and validation of analytical methodology for evaluation of NovaBupi® content in the poly-lactide-co-glycolide nanospheres (PLGA-NS) by high performance liquid chromatography. The separation was made using the reversed-phase column LC-18, acetonitrile/phosphate buffer 85:15 v/v as mobile phase and detection at 220 nm. The results obtained show that the analytical methodology is accurate, reproducible, robust and linear over the concentration range 10-220.0 g/mL of NovaBupi®. The method was applied to determine the encapsulation efficiency and evaluate the release profile of NovaBupi®, showing good results. Universidade Estadual de Campinas Departamento de Bioquímica Universidade Estadual Paulista Júlio de Mesquita Filho Departamento de Engenharia Ambiental Universidade Estadual Paulista Júlio de Mesquita Filho Departamento de Engenharia Ambiental
- Published
- 2008
21. Characterization of the inclusion complex ropivacaine: β-cyclodextrin
- Author
-
Leonardo Fernandes Fraceto, Thelma A. Pertinhez, Daniele Ribeiro de Araujo, Marcos Moisés Gonçalves, Luciana Zanella, Eneida de Paula, Carolina Morales Moraes, Universidade Estadual Paulista (Unesp), Universidade de Sorocaba (UNISO), Universidade Estadual de Campinas (UNICAMP), and Universidade de Parma
- Subjects
lcsh:Chemistry ,ropivacaine ,lcsh:QD1-999 ,cyclodextrin ,Ropivacaine ,Chemistry ,Stereochemistry ,medicine ,Physical chemistry ,General Chemistry ,Longitudinal Relaxation Time ,NMR ,medicine.drug - Abstract
Submitted by Guilherme Lemeszenski (guilherme@nead.unesp.br) on 2013-08-22T18:48:40Z No. of bitstreams: 1 S0100-40422007000500028.pdf: 374745 bytes, checksum: a9063a55f3da9cef21ac1cf2089e14a1 (MD5) Made available in DSpace on 2013-08-22T18:48:40Z (GMT). No. of bitstreams: 1 S0100-40422007000500028.pdf: 374745 bytes, checksum: a9063a55f3da9cef21ac1cf2089e14a1 (MD5) Previous issue date: 2007-10-01 Made available in DSpace on 2013-09-30T19:38:41Z (GMT). No. of bitstreams: 2 S0100-40422007000500028.pdf: 374745 bytes, checksum: a9063a55f3da9cef21ac1cf2089e14a1 (MD5) S0100-40422007000500028.pdf.txt: 23611 bytes, checksum: 5443ea391531e33f28162a5b020d6105 (MD5) Previous issue date: 2007-10-01 Submitted by Vitor Silverio Rodrigues (vitorsrodrigues@reitoria.unesp.br) on 2014-05-20T15:10:23Z No. of bitstreams: 2 S0100-40422007000500028.pdf: 374745 bytes, checksum: a9063a55f3da9cef21ac1cf2089e14a1 (MD5) S0100-40422007000500028.pdf.txt: 23611 bytes, checksum: 5443ea391531e33f28162a5b020d6105 (MD5) Made available in DSpace on 2014-05-20T15:10:23Z (GMT). No. of bitstreams: 2 S0100-40422007000500028.pdf: 374745 bytes, checksum: a9063a55f3da9cef21ac1cf2089e14a1 (MD5) S0100-40422007000500028.pdf.txt: 23611 bytes, checksum: 5443ea391531e33f28162a5b020d6105 (MD5) Previous issue date: 2007-10-01 Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Characteriza of the inclusion complex ropivacaine: β-cyclodextrin. Ropivacaine (RVC) is a widely used local anesthetic. The complexation of RVC with β-cyclodextrin (β-CD) is of great interest for the development of more efficient local anesthetic formulations. The present work focuses on the characterization of the RVC:β-CD complex by nuclear magnetic resonance (NMR). The stoichiometry of the complex is 1:2 RVC:β-CD. DOSY-NMR shows that the association constant is 55.5 M-1. Longitudinal relaxation time results show that RVC changes its mobility in the presence of β-CD. This study is focused on the physicochemical characterization of inclusion complexes that are potentials options for pain treatment. Universidade Estadual Paulista Júlio de Mesquita Filho Departamento de Engenharia Ambiental Universidade de Sorocaba Universidade Estadual de Campinas Instituto de Biologia Departamento de Bioquímica Universidade de Parma Departamento de Medicina Experimental Universidade Estadual Paulista Júlio de Mesquita Filho Departamento de Engenharia Ambiental
- Published
- 2007
22. Preperetion and physico-chemical characterization of inclusion complexes between local anesthetics and hydroxypropyl-b-cyclodextrin
- Author
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Priscila Abrami, Marcos Moisés Gonçalves, Leonardo Fernandes Fraceto, Newton Andréo Filho, Carolina Morales Moraes, Eneida de Paula, Sergio Antonio Fernandes, Universidade de Sorocaba (UNISO), Universidade Estadual de Campinas (UNICAMP), and Universidade Estadual Paulista (Unesp)
- Subjects
chemistry.chemical_classification ,Cyclodextrin ,cyclodextrin ,Stereochemistry ,Chemistry ,lidocaine ,General Chemistry ,S(-) Bupivacaine ,Medicinal chemistry - Abstract
Submitted by Guilherme Lemeszenski (guilherme@nead.unesp.br) on 2013-08-22T18:48:39Z No. of bitstreams: 1 S0100-40422007000400005.pdf: 448201 bytes, checksum: f4a671aaf392f34bfcfc24bd0a137e0b (MD5) Made available in DSpace on 2013-08-22T18:48:39Z (GMT). No. of bitstreams: 1 S0100-40422007000400005.pdf: 448201 bytes, checksum: f4a671aaf392f34bfcfc24bd0a137e0b (MD5) Previous issue date: 2007-08-01 Made available in DSpace on 2013-09-30T19:38:40Z (GMT). No. of bitstreams: 2 S0100-40422007000400005.pdf: 448201 bytes, checksum: f4a671aaf392f34bfcfc24bd0a137e0b (MD5) S0100-40422007000400005.pdf.txt: 40304 bytes, checksum: 5562327cb297491cea116d89bb91bffb (MD5) Previous issue date: 2007-08-01 Submitted by Vitor Silverio Rodrigues (vitorsrodrigues@reitoria.unesp.br) on 2014-05-20T15:10:23Z No. of bitstreams: 2 S0100-40422007000400005.pdf: 448201 bytes, checksum: f4a671aaf392f34bfcfc24bd0a137e0b (MD5) S0100-40422007000400005.pdf.txt: 40304 bytes, checksum: 5562327cb297491cea116d89bb91bffb (MD5) Made available in DSpace on 2014-05-20T15:10:23Z (GMT). No. of bitstreams: 2 S0100-40422007000400005.pdf: 448201 bytes, checksum: f4a671aaf392f34bfcfc24bd0a137e0b (MD5) S0100-40422007000400005.pdf.txt: 40304 bytes, checksum: 5562327cb297491cea116d89bb91bffb (MD5) Previous issue date: 2007-08-01 Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) S(-) Bupivacaine (S(-)BVC) and Lidocaine (LDC) are widely used local anesthetics (LA). Hydroxypropyl beta-cyclodextrin (HP-beta-CD) is used as a drug-carrier system. The aim of this work was to characterize inclusion complexes between LA and HP-beta-CD. The affinity constants determined at different pHs show favourable complexation. The release kinetics experiments showed that S(-)BVC and LDC changed the released profiles in the presence of HP-beta-CD. Nuclear magnetic resonance experiments gave information about the interaction between LA and the cyclodextrin cavity. This study focused on the physicochemical characterization of drug-delivery formulations that come out as potentially new therapeutic options for pain treatment. Universidade de Sorocaba Universidade Estadual de Campinas Instituto de Biologia Departamento de Bioquímica Universidade Estadual Paulista Júlio de Mesquita Filho Departamento de Engenharia Ambiental Universidade Estadual Paulista Júlio de Mesquita Filho Departamento de Engenharia Ambiental
- Published
- 2007
23. Study of the interaction between hydroxymethylnitrofurazone and 2-hydroxypropyl-beta-cyclodextrin
- Author
-
Leonardo Fernandes Fraceto, Renata de Lima, Renato Grillo, Carolina Morales Moraes, Nathalie Ferreira Silva de Melo, André Henrique Rosa, Carla M. S. Menezes, and Elizabeth Igne Ferreira
- Subjects
Magnetic Resonance Spectroscopy ,Clinical Biochemistry ,Analytical chemistry ,Pharmaceutical Science ,High-performance liquid chromatography ,Analytical Chemistry ,Inclusion compound ,chemistry.chemical_compound ,Phase (matter) ,Drug Discovery ,Drug Interactions ,Solubility ,Spectroscopy ,Chromatography, High Pressure Liquid ,chemistry.chemical_classification ,Cyclodextrin ,Molecular Structure ,Chemistry ,Nitrofurazone ,beta-Cyclodextrins ,Oligosaccharide ,2-Hydroxypropyl-beta-cyclodextrin ,Stability constants of complexes ,Stoichiometry ,Nuclear chemistry - Abstract
Chagas disease is a serious health problem in Latin America. Hidroxymethylnitrofurazone (NFOH) is a nitrofurazone prodrug more active than nitrofurazone against Trypanosoma cruzi. However, NFOH presents low aqueous solubility, high photodecomposition and high toxicity. The present work is focused on the characterization of an inclusion complex of NFOH in 2-hydroxypropyl-beta-cyclodextrin (HP-beta-CD). The complexation with HP-beta-CD was investigated using reversed-phase liquid chromatography, solubility isotherms and nuclear magnetic resonance. The retention behavior was analyzed on a reversed-phase C(18) column, using acetonitrile-water (20/80, v/v) as the mobile phase, in which HP-beta-CD was incorporated as a mobile phase additive. The decrease in the retention times with increasing concentrations of HP-beta-CD enables the determination of the apparent stability constant of the complex (K=6.2+/-0.3M(-1)) by HPLC. The solubility isotherm was studied and the value for the apparent stability constant (K=7.9+/-0.2M(-1)) was calculated. The application of continuous variation method indicated the presence of a complex with 1:1 NFOH:HP-beta-CD stoichiometry. The photostability study showed that the formation of an inclusion complex had a destabilizing effect on the photodecomposition of NFOH when compared to that of the "free" molecule in solution. The mobility investigation (by NMR longitudinal relaxation time) gives information about the complexation of NFOH with HP-beta-CD. In preliminary toxicity studies, cell viability tests revealed that inclusion complexes were able to decrease the toxic effect (p
- Published
- 2007
24. [Complexation of 50% enantiomeric excess (S75-R25) bupivacaine with cyclodextrins and spinal block anesthesia in rats.]
- Author
-
Daniele Ribeiro de, Araujo, Angélica de Fátima de Assunção, Braga, Carolina Morales, Moraes, Leonardo Fernandes, Fraceto, and Eneida de, Paula
- Abstract
In order to prolong the action and reduce systemic toxicity, formulations of local anesthetic (LA) complexed with cyclodextrins (CD) have been developed. This study determined the physical-chemical characterization and evaluated the effects of inclusion complexes of racemic bupivacaine (S50-R50) and 50% enantiomeric excess (S75-R25) bupivacaine with hydroxypropil-beta-cyclodextrin (HP-beta-CD) in rats, and comparing them with the solutions currently used in the clinical practice.Inclusion complexation of S75-R25 with HP-beta-CD (equimolar ratio 1:1) was characterized by phase-solubility studies varying the concentrations of HP-beta-CD and the temperature. Affinity constants (K) for HP-beta-CD and the thermodynamic parameters for complexation were determined. Motor and sensitive anesthesias were evaluated through the subarachnoid administration of the formulations in the concentration of 0.5%.Inclusion complexation was observed through the increase in aqueous solubility of LA in different temperatures and concentrations of HP-beta-CD. The in vivo tests demonstrated that S50-R50HP-beta-CD and S75-R25HP-beta-CD reduced latency (p0.001) without changing the recovery time of the motor block, time for maximal effect, and total effect of the drugs. Besides, both formulations increased the intensity (1.5 times, p0.001) and prolonged the duration of analgesia compared to the free drugs.The complexes S50-R50HP-beta-CD and S75-R25HP-beta-CD potentiated the differential nervous block, and can be used to reduce the frequency of administration or the dose of the LA to induce the same effect. The formulation containing enantiomeric excess (S75-R25) bupivacaine showed to be interesting in the development of safer formulations, and useful for the treatment of acute pain in the postoperative period.
- Published
- 2005
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