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Nanopartículas lipídicas sólidas contendo genisteína para uso tópico

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Previous issue date: 2012-02-28 / Conselho Nacional de Pesquisa e Desenvolvimento Científico e Tecnológico - CNPq / Genistein (GEN), isoflavone contained in soybeans, shows activity against a
large number of cancers, including skin cancer. However, to be used topically it is
essential the association of GEN in an appropriate formulation. The aim of this study
was the development and characterization of solid lipid nanoparticles (SLN) contends
genistein for topical application. A bioanalytical method was developed and validated
for GEN quantification in skin layers with High Performance Liquid Chromatographer
(HPLC) with UV detection. The SLN was obtained with glyceryl behenate,
polysorbate 80, sorbitan trioleate and different amounts of cetylpyridinium chloride
(CPC) (0.5 - 0.05%). The characteristics in terms of particle size, size distribution,
zeta potential, entrapment efficiency and drug recovery were evaluated. In vitro
release, passive and iontophoretic, skin permeation studies were performed.
Cytotoxicity studies were carried out in melanoma cells (B16F10) with free drug and
SLN with and without GEN. The analytical method was linear in the concentration
range of 0.1 to 60 mg/mL. Limit of quantification was 100 ng/mL for both skin
layers. Recovery of the drug ranged from 95.57 to 97.57%. The method was able to
analyze the GEN without suffering interference from endogenous skin
components. SLN loaded with GEN showed positive surface (+ 23 mV) and average
size of 343 nm. Particles were obtained with high entrapment efficiency (93%) and
drug load was 5.45%. In vitro release studies demonstrated that the release of GEN
from SLN occurs in two stages with a large amount of drug released within the first
six hours, followed by a slow release of the remaining drug in the lipid matrix of SLN
in the following hours. When administered in the skin, during in vitro passive
permeation studies, the SLN increased retention of GEN in stratum corneum and
remaining skin compared with free GEN. After iontophoresis application in
formulation of SLN containing GEN thirteen times more GEN was retained on stratum
corneum and three times more drug was retained on remaining skin. In cellular
cytotoxicity studies SLN favored the increase of interaction of drug with the cells and
the cytotoxicity was concentration-dependent. Thus, GEN loaded SLN increased drug
skin permeation and retention and shows to be a potential formulation for topical
application. / A genisteína (GEN), isoflavona contida nos grãos da soja, apresenta atividade
contra um grande número de tipos de câncer, incluindo o câncer de pele. No
entanto, para ser usada topicamente é fundamental que a GEN esteja associada a
uma formulação adequada. O objetivo deste trabalho foi desenvolver e caracterizar
nanopartículas lipídicas sólidas (NLS) contendo genisteína para aplicação tópica.
Para a quantificação da genisteína nas diferentes camadas da pele foi desenvolvida
e validada uma metodologia bioanalítica em cromatografia líquida de alta eficiência
(CLAE) com detecção no UV. As NLS foram obtidas com behenato de glicerila,
polissorbato 80, trioleato de sorbitano e tensoativo catiônico cloreto de cetilpiridínio
(CPC) em diferentes quantidades (0,5 – 0,05%). As NLS foram caracterizadas
quanto ao tamanho, PdI, potencial zeta, eficiência de encapsulação e recuperação.
Foram realizados estudos in vitro de liberação e permeação cutânea passiva e
iontoforética. Estudos de citotoxicidade foram realizados em linhagem de melanoma
(B16F10) com fármaco livre e NLS com e sem GEN. O método de quantificação do
fármaco mostrou-se linear na faixa de concentração de 0,1 a 60 μg/mL. O limite de
quantificação foi de 100 ng/mL para ambas as camadas da pele. A recuperação do
fármaco variou entre 95,57 a 97,57%. Ainda, o método foi capaz de analisar a GEN
sem sofrer interferência dos componentes endógenos da pele. As NLS carregadas
com fármaco apresentaram carga superficial positiva (+ 23 mV) e tamanho médio de
343 nm. Também foram obtidas partículas com alta eficiência de encapsulação
(93%) e carga de fármaco de 5,45%. Os estudos de liberação in vitro demonstraram
que a liberação da GEN a partir das NLS ocorre em duas fases, com uma grande
quantidade de fármaco liberada nas seis primeiras horas, seguida por uma liberação
lenta do restante do fármaco da matriz lipídica das NLS nas horas seguintes.
Quando administrada na pele, nos estudos de permeação passiva in vitro, as NLS
aumentaram a retenção da GEN tanto no estrato córneo quanto na pele
remanescente em comparação à administração da GEN livre. Após a aplicação da
iontoforese na formulação de NLS contendo GEN, treze vezes mais GEN ficou retida
no EC e três vezes mais fármaco ficou retido na pele remanescente. Nos estudos de
citotoxicidade, as NLS favoreceram o aumento da interação do fármaco com as
células e a citotoxicidade foi concentração-dependente. Deste modo, a
encapsulação da GEN em NLS aumentou a permeação e retenção do fármaco na
pele, demonstrando assim, potencial para aplicação tópica.

Identiferoai:union.ndltd.org:IBICT/oai:repositorio.bc.ufg.br:tde/3041
Date28 February 2012
CreatorsSilva, Lorena Maione
ContributorsLima, Eliana Martins, Taveira, Stephânia Fleury
PublisherUniversidade Federal de Goiás, Programa de Pós-graduação em Ciências Farmacêuticas (FF), UFG, Brasil, Faculdade Farmácia - FF (RG)
Source SetsIBICT Brazilian ETDs
LanguagePortuguese
Detected LanguagePortuguese
Typeinfo:eu-repo/semantics/publishedVersion, info:eu-repo/semantics/masterThesis
Formatapplication/pdf
Sourcereponame:Biblioteca Digital de Teses e Dissertações da UFG, instname:Universidade Federal de Goiás, instacron:UFG
Rightshttp://creativecommons.org/licenses/by-nc-nd/4.0/, info:eu-repo/semantics/openAccess
Relation824936988196152412, 600, 600, 600, 600, 6010281161524209375, 6997636413449754996, -2555911436985713659, ABISMAÏL, B.; CANSELIER, J.P.; WILHELM, A.M.; DELMAS, H.; GOURDON, C. Emulsification by ultrasound: drop size distribution and stability B. Ultrasonics Sonochemistry, v. 6, p. 75-83, 1999. ADLERCREUTZ, H.; MARKKANEN, H.; WATANABE, S. Plasma concentrations of phyto-oestrogens in Japanese men. Lancet, v. 342, p. 1209-1210, 1993. AULTON, M. E. Delineamento de Formas Farmacêuticas, 2. ed. Porto Alegre: Artemd, 2005, p.677. BANERJEE, S.; LI, Y.; WANG, Z.; SARKAR, F. H. Multi-targeted therapy of cancer by Genistein. Cancer Letters, v. 269, p. 226–242, 2008. BOUWSTRA, J. A.; HONEYWELL-NGUYEN, P. L. Skin structure and mode of action of vesicles. Adv. Drug Deliv., v. 54 (Suppl1), p. S41–S55, 2002. BOUWSTRA, J. A.; van den Berghe, B. A.; SUHONEN, M. Topical application of drugs: mechanisms involved in chemical enhancement. J. Recept. Signal Transduct, Res. 21 (2–3), p. 259–286, 2001. BRASIL. Instituto Nacional do Câncer. INCA/MS. Disponível em:< http://www2.inca.gov.br/wps/wcm/connect/inca/portal/home> Acesso em: 15/11/2011. CARUTHERS, S. D.;1,2, WICKLINE, S. A.; LANZA, G. M. L. Nanotechnological applications in medicine. Current Opinion in Biotechnology, v. 18, p. 26-30, 2007. CÉSAR, I. C.; BRAGA, F. C.; SOARES, C. D. V.; NUNAN, E. A.; PIANETTI, G. A.; CONDESSA, F. A.; BARBOSA, T. A. F.; CAMPOS, L. M. M. Development and validation of a RP-HPLC method for quantification of isoflavone aglycones in hydrolyzed soy dry extracts. Journal of Chromatography B, v. 836, p.74-78, 2006. CHEN, H.; CHANG, X.; DU, D.; LIU, W.; LIU, J.; WENG, T.; YANG, Y.; XU, H.; YANG, X.Podophyllotoxin-loaded solid lipid nanoparticles for epidermal targeting. J. Control. Release, v.110, n. 2, p. 296–306, 2006. CHIEN, Y. W. Novel Drug Delivery Systems, 2. ed. New York: Marcel Dekker, Inc, 2001. p. 300-375. DUBHASHI, S.S.; VAVIA, P.R. HPTLC method to study skin permeation of acyclovir. Journal of Pharmaceutical and Biomedical Analysis, v. 23, p.1017-1022, 2000. ECHEVARRÍA, L.; BANCO-PRÍETO, M. J.; CAMPANERO, M. A.; SANTOYO, S.; YGARTUA, P. Development and validation of a liquid chromatographic method for in vitro mupirocin quantification in both skin layers and percutaneous penetration studies. Journal of Chromatography B, v.796, p. 233-241, 2003. ESCOBAR-CHÁVEZ, J. J.; MERINO-SANJUÁN, V.; LÓPEZ-CERVANTES, M.; URBAN-MORLAN, Z.; PIÑÓN-SEGUNDO, E.; QUINTANAR-GUERRERO, D.; GANEM-QUINTANAR, A. The Tape-Stripping Technique as a Method for Drug Quantification in Skin. J Pharm Pharmaceut Sci, v. 11, n. 1, p. 104-130, 2008. FANG, J. Y.; LEU, Y. L.; CHANG, C.C.; LIN, C.H.; TSAI, Y. H. Lipid nano/submicron emulsions as vehicles for topical flurbiprofen delivery. Drug Deliv, v.11, p.97–105, 2004. FANG, JIA-YOU.; FANG, CHIA-LANG.; LIU, CHI-HSIEN.; SU, YU-HAN. Lipid nanoparticles as vehicles for topical psoralen delivery: Solid lipid nanoparticles (SLN) versus nanostructured lipid carriers (NLC). European Journal of Pharmaceutics and Biopharmaceutics, v. 70, p. 633–640, 2008. FENG, SI-SHEN.; CHIEN, S. Chemotherapeutic engineering: Application and further development of chemical engineering principles for chemotherapy of cancer and other diseases. Chemical Engineering Science, v. 58, p. 4087 – 4114, 2003. FERNANDEZ, C.; MARTI-MESTRES, G.; MESTRES, J. P.; MAILLOLS, H. LC analysis of benzophenone-3: II application to determination of 'in vitro' and 'in vivo' skin penetration from solvents, coarse and submicron emulsions. Journal of Pharmaceutical and Biomedical Analysis, v. 24, n. 1, p.155-165, 2000. FDA. Center for Drug Evaluation and Research, United States Food and Drug Administration. Guidance for Industry: Bioanalytical Method Validation. 2001. Disponível em: <http://www.fda.gov/cder/guidance/index.htm>. Acesso em: março, 2009. FDA. Center for Drug Evaluation and Research, United States Food and Drug Administration. Q2B Validation of Analytical Procedures: Methodology Guidance for Industry: Bioanalytical Method Validation. 1996. Disponível em: < http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Gui dances/ucm073384.pdf>. Acesso em: março, 2009. FIGUEIREDO, L. C.; CORDEIRO, L. N.; ARRUDA, A. P.; CARVALHO, M. D. F.; RIBEIRO, E. M.; COUTINHO, H. D. M. Câncer de pele: estudo dos principais marcadores moleculares do melanoma cutâneo. Revista Brasileira de Cancerologia, v. 49, n. 3, p. 179-183, 2003. FOFTIS, T.; PEPPER,M.; ADLERCREUTZ, H.; FLEISCHMANN, G.; HASE, T.; MONTESANO, R.; SCHWEIGERER, L. Genistein, a dietary-derived inhibitor of in vitro angiogenesis. Medical Sciences, v. 90, p. 2690-2694, 1993. FUKUTAKE, M.; TAKAHASHI, M.; ISHIDA, K.; KAWAMURA, H.; SUGIMURA, T.; WAKABAYASHI, K. Quantification of genistein and genistin in soybean and soybeans products. Food and Chemical Toxicology, v. 34, p. 457-461, 1996. GAO, Y.; GU, W.; CHEN, L.; XU, Z.; LI, Y. The role of daidzein-loaded sterically stabilized solid lipid nanoparticles in therapy for cardio-cerebrovascular diseases. Biomaterials, v. 29, p. 4129–4136, 2008. GASCO, M.R. Method of producing solid lipid microspheres having narrow size distribution. US Patent No. 5250236, 1993. GEORGETTI, S. R.; CASAGRANDE, R.; VERRI, W. A. Jr.; LOPEZ, R. F.; FONSECA, M. J. Evaluation of in vivo efficacy of topical formulations containing soybean extract. Int. J. Pharm., v. 352 (1-2), p.189-196, 2008. GLIKFELD, P.; CULLANDER, C.; HINZ, R.S.; GUY, R.H. A new system for in vitro studies of iontophoresis. Pharm.Res., v. 5, p. 443–446, 1988. GRATIERI, T.; GELFUSO, G.M.; LOPEZ, R.F.V. Princípios básicos e aplicação da iontoforese na penetração cutânea de fármacos. Quim. Nova, v. 31, p. 1490-1498, 2008. JENSEN L. B.; PETERSSON, K.; NIELSEN, H. M. In vitro penetration properties of solid lipid nanoparticles in intact and barrier-impaired skin. European Journal of Pharmaceutics and Biopharmaceutics, v. 79, p. 68–75, 2011. KANG, S.; CHUNG,J. H.; LEE, J. H.; FISHER, G. J.; SHENGWAN, Y.; DUELL, E. A.; VOORHEES, J. J. Topical N-Acetyl Cysteine and Genistein Prevent Ultraviolet-Light- Induced Signaling That Leads to Photoaging in Human Skin in vivo. The Journal of Investigative Dermatology, v. 120, n. 5, 2003. KIGUCHI, K.; CONSTANTINOU, A.; HUBERMAN, E. Genistein induced cell differentiation and protein-linked DNA strand breakage in human melanoma cells. Cancer Commun, v.2 p. 271–278, 1990. KIM, B. D.; NA, K.; CHOI, H. K. Preparation and characterization of solid lipid nanoparticles (SLN) made of cacao butter and curdlan. Eur. J. Pharm. Sci., v. 24, p.199–205, 2005. Klein, C. B.; King, A. A. Genistein genotoxicity: critical consideration of in vitro exposure dose. Toxicology and Applied Pharmacology, v. 224, p. 1-11, 2007. KORTING, H. C.; SCHAEFER-KORTING, M. Carriers in the topical treatment of skin disease. Handb. Exp. Pharmacol., v.197, p. 435–468, 2010. KSYCINSKA, H.; SOBIK, B.; POPIOLKIEWICZ, J.; POLKOWSKI, K.; KRZECZYNSKI, P.; RAMZA, J.; PUCKO, W.; GRYNKIEWICZ, .G. Determination of new derivatives of genistein in culture media by liquid chromatography. J. of Chromatography B, v. 799, p. 217-231, 2004. KULKARNI, S.B.; BANGA, A.K.; BETAGERI, G.V. Delivery of liposome encapsulated colchicine across human cadaver skin using iontophoresis. Pharm. Res., v. 13, p. S361–S369, 1996. KUO, YUNG-CHIH.; CHEN, HUNG-HAO. Entrapment and release of saquinavir using novel cationic solid lipid Nanoparticles. International Journal of Pharmaceutics, v. 365, p. 206–213, 2009. KUO, Y.C.; LIN, T.W. Electrophoretic mobility, zeta potential, and fixed charge density of bovine knee chondrocytes, methylmethacrylate–sulfopropylmethacrylate, polybutylcyanoacrylate, and solid lipid nanoparticles. J. Phys. Chem. B, v. 110, p. 2202–2208, 2006. LADEMANN, J.; RICHTER, H.; TEICHMANN, A.; OTBERG, N.; BLUME-PEYTAVI, U.; LUENGO, J.; WEISS, B.; SCHAEFER, U. F.; LEHR, C.M.; WEPF, R.; STERRY, W. Nanoparticles-an efficient carrier for drug delivery into the hair follicles. Eur. J. Pharm. Biopharm., v.66, p. 159–164, 2007. LAMPE,J. W.; NISHINO, Y.; RAY, R. M.; WU,C.; LI, W.; LIN, M. G.; GAO, D. L.; HU, Y.; SHANNON, J.; STLSBERG, H.; PORTER, P. L.; FRANKEFELD, C. L.; WÄHÄLÄ, K.; THOMAS, D. B. Plasma isoflavones and fibrocystic breast conditions and breast cancer among women in Shanghai, China. Cancer Epidemiol. Biomarkers Prev., v.16, p. 2579–2586, 2007. LIGGINS, J.; BLUCK, L. J.; RUNSWICK, S.; ATKINSON, C.; COWARD, W. A.; BINGHAM, S. A. Daidzein and genistein contents of vegetables. British Journal of Nutrition, v.84, 717-725, 2000. LIU, W.; HU, W.; LIU, W.; XUW, C.; XU, H.; YANG, X. Investigation of the carbopol gel of solid lipid nanoparticles for the transdermal iontophoretic delivery of triamcinolone acetonide acetate. International Journal of Pharmaceutics, v. 364, p. 135-141, 2008. LOPES, L. B.; REED, R. A simple and rapid method to assess lycopene in multiple layers of skin samples. Biomedical Chromatography, v.24, p.154-159, 2009. MARENGO, E.; CAVALLI, R.; CAPUTO, O.; RODRIGUEZ, L.; GASCO, M.R. Scaleup of preparation process of solid lipid nanospheres. Part I. International Journal of Pharmaceutics, v. 205 (1-2), p. 3-13, 2000. MARQUES, M.R.C. Dissolução de medicamentos. In: ____ Ciências Farmacêuticas, Biofarmacotécnica, 1 ed. Rio de Janeiro: Guanabara-Koogan, 2009. cap. 7. MORAES, S. L.; REZENDE, M. O. O. Determinação da concentração micelar crítica de ácidos húmicos por medidas de condutividade e espectroscopia. Quim. Nova, v. 27, n. 5, p. 701-705, 2004 MONON, L. G.; KUTTAN, R.; NAIR, M. G. Effect of isoflavone genistein and daidzein in the inhibition of lung metastasis in mice induced by B16F–10 melanoma cells. Nutr. Cancer, v. 30, p. 74–77, 1998. MEHNERT, W.; MÄDER, K. Solid lipid nanoparticles production, characterization and applications. Advanced Drug Delivery Reviews, v. 47, p. 165-196, 2001. MICHAELS, A. S.; CHANDRASEKARAN, S. K.; SHAW, J. E. Drug permeation through human skin: theory and in vitro experimental measurement, AlChE J., v. 21, p. 985–986, 1975. MOORE, A.; BASILION, J.P.; CHIOCCA, E.A.; WEISSLEDER, R. Measuring transferring receptor gene expression by NMR imaging. Biochim. Biophys. Acta, v. 1402, p. 239–249, 1998. MOSER, K.; KRIWER, K.; NAIK, A.; KALIA, Y. N.; GUY, R. H. Passive skin penetration enhancement and its quantification in vitro. European Journal of Pharmaceutics and Biopharmaceutcs, v. 52, p.103-112, 2001. MOSMANN, T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J. Immunol. Methods, v. 65, p. 55-63, 1987. MUCHOW, M.; MAINCENT, P.; MÜLLER, R. H. Lipid Nanoparticles with a Solid Matrix (SLN®, NLC®, LDC®) for Oral Drug Delivery. Drug Development and Industrial Pharmacy, v. 34, p.1394–1405, 2008. MÜLLER, R. H.; MÄDER, K.; GOHLA, S. Solid lipid nanoparticles (SLN) for controlled drug delivery - a review of the state of the art. European Journal of Pharmaceutics and Biopharmaceutics, v. 50, p. 161-177, 2000. MÜLLER, R. H.; RADTKE, M.; WISSING, S. A. Solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) in cosmetic and dermatological preparations. Advanced Drug Delivery Reviews, v.54, Suppl. 1, p. S131-S155, 2002. OLBRICH, C.; BAKOWSKY, U.; LEHR, CLAUS-MICHAEL.; MU¨LLER, R. H.; KNEUER, C. Cationic solid-lipid nanoparticles can efficiently bind and transfect plasmid DNA. Journal of Controlled Release, v. 77, p. 345-355, 2001. OMS. Organização Mundial de Saúde. Disponível em: < http://www.who.int/topics/cancer/en/>. Acesso em: 19/11/2011. PAVESE, J. M.; FARMER, R. L.; BERGAN, R.C. Inhibition of cancer cell invasion and metastasis by genistein.Cancer Metastasis Rev, v. 29, p.465–482, 2010. PERKIN, A. G.: NEWBURY, F. G. The colouring matters contained in dyer’s broom (Genista tinctoria) and heather (Calluna vulgaris). Journal of the Chemical Society, v.75, p. 830–839, 1899. POUTON, C. W.; PORTER, C. J. H. Formulation of lipid-based delivery systems for oral administration: Materials, methods and strategies. Advanced Drug Delivery Reviews, v. 60, p. 625–637, 2008. PROW, T. W.; GRICE, J. E.; LIN, L. L.; FAYE, R.; BUTLER, M.; BECKER, W.; WURM, E. M.T.; YOONG, C.; ROBERTSON, T.A.; SOYER, H. P.; ROBERTS, M. S. Nanoparticles and microparticles for skin drug delivery. Advanced Drug Delivery Reviews, v. 63, p. 470-491, 2011. PURI, D.; BHANDARI. A.; SHARMA, P.; CHOUDHARY, D. Lipid nanoparticles (sln, nlc): a novel approach for cosmetic and dermal pharmaceutical. Journal of Global Pharma Technology, v. 2, n. 5, p. 1-15, 2010. ROBERTS, M. S.; CROSS, S. E.; PELLETT, M. A. Skin transport., New York: Marcel Dekker, Inc, 2002. p.89-195. SALTI, G.I.; GREWAL, S.; MEHTA, R. R.; DAS GUPTA, T. K.; BODDIE, A. W.; CONSTANTINOU, JR, A.I. Genistein induces apoptosis and topoisomerase IImediated DNA breakage in colon cancer cells. European Journal of Cancer, v. 36, p. 796±802, 2000. SCHOEPF, U.; MARECOS, E.; MELDER, R.; JAIN, R.; WEISSLEDER, R. Intracellular magnetic labeling of lymphocytes for in vivo trafficking studies. BioTechniques, v. 24, p.642, 1998. SENYIGIT, T.S.; PADULA, C.; OZER, O.; SANTI, P. Different approaches for improving skin accumulation of topical corticosteroids. International Journal of Pharmaceutics, v. 380, p. 155-160, 2009. SHAJI, J.; JAIN, V. SOLID LIPID NANOPARTICLES: A NOVEL CARRIER FOR CHEMOTHERAPY. Int J Pharmacy and Pharm Sci, v..2, Suppl. 3, p. 817, 2010. SHARMA, P.; GANTA, S.; DENNY, W. A.; GARG, S. Formulation and pharmacokinetics of lipid nanoparticles of a chemically sensitive nitrogen mustard derivative: Chlorambucil International Journal of Pharmaceutics, v. 367, p.187– 194, 2009. SILVA, A. P.; NUNES, B. R.; DE OLIVEIRA, M. C.; KOESTER, L. S.; MAYORGA, P.; BASSANI, V. L.; TEIXEIRA, H. F. Development of topical nanoemulsions containing the isoflavone genistein. Pharmazie, v.64, n.1, p.32-35, 2009. SILVA, A. P. C.; KOESTER, L. S.; MAYORGA, P.; BASSANI, V. L.; TEIXEIRA, H. Development and validation of a LC method for determination of genistein in topical nanoemulsions. Pharmazie, v. 62, p. 732–734, 2007. SILVA, J. L.; APOLINÁRIO, A. C.; SOUZA, M. S. R.; DAMASCENO, B. P. G. L.; MEDEIROS, A. C. D. Administração cutânea de fármacos: desafios e estratégias para o desenvolvimento de formulações transdérmicas. Rev Ciênc Farm Básica Apl., v. 31, n. 3, p. 125-131, 2010. SOUTO, E.B.; MÜLLER, R.H. The use of SLN and NLC as topical particulate carriers for imidazole antifungal agents. Pharmazie, v. 61, p. 431–437, 2006. SOUZA, L. G.; SILVA, E. J.; MARTINS, A. L. L.; MOTA, M. F.; BRAGA, R. C.; LIMA, E. M.; VALADARES, M. C.; TAVEIRA, S. F.; MARRETO, R. N. Development of topotecan loaded lipid nanoparticles for chemical stabilization and prolonged release. European Journal of Pharmaceutics and Biopharmaceutics, v. 79, p. 189–196, 2011. TABATT, K.; SAMETI, M.; OLBRICH, C.; MULLER, R. H.; LEHR, C. Effect of cationic lipid and matrix lipid composition on solid lipid nanoparticle-mediated gene transfer. European Journal of Pharmaceutics and Biopharmaceutics, v. 57, p.155–162, 2004. TAVEIRA, S.F.; NOMIZO, A.; LOPEZ, R.F.V. Effect of the iontophoresis of a chitosan gel on doxorubicin skin penetration and cytotoxicity. Journal of Controlled Release, v. 134, p. 35-40, 2009. TESSELAAR, E.; SJOBERG, F.; Transdermal iontophoresis as an in-vivo technique for studying microvascular physiology. Microvascular Research, v. 81, p. 88-96, 2011. THOMAS, B. F.; ZEISEL, S. H.; BUSBY, M. G.; HILL, J. M.; MITCHELL, R. A.; SCHEFFLER, N. M.; BROWN, S. S.; BLOEDEN, L. T.; DIX, K. J.; JEFFCOAT, A. R. Quantitative analysis of the principle soy isoflavones genistein, daidzein and glycitein, and their primary conjugated metabolites in human plasma and urine using reversedphase high-performance liquid chromatography with ultraviolet detection. Journal of Chromatography B, v.760, p. 191-205, 2001. TOUITOU, E.; MEIDAN, V. M.; HORWITZ, E. Methods for quantitative determination of drug localized in the skin. Journal of Controlled Release, v.56, p. 7-21, 1998. UNGAR, Y.; OSUNDAHUNSI, O. F.; SHIMONI, E. Thermal Stability of genistein and daidzein and its effect on their antioxidant activity. Journal of Agricultural and Food Chemistry, v.15, p. 4394-4399, 2003. VENUGANTI, V. V. e PERUMAL, O. P. Drug delivery nanoparticles formulations and characterization. New York: Informa Healthcare, Inc, 2009, 418p. WAGNER, V.; DULLAART, A.; BOCK, A.; ZWECK, A. The emerging nanomedicine landscape. Nature Biotechnology,v. 24, n. 10, 2006. WEI, H.; SALADI, R.; LU, Y.; WANG, Y.; PALEP, S. R.; MOORE, J.; PHELPS, R.; SHYOUNG, E.; LEBWOHL, M. Isoflavone genistein: photoprotection and clinical implications in dermatology. J. Nutr, v 133, p. 3811S-3819S, 2003. WEISSLEDER, R.; CHENG, H.C.; BOGDANOVA, A.; BOGDANOV, A. Magnetically labeled cells can be detected by MR imaging. J. Magn. Reson. Imaging, v. 7, p.258–263, 1997. WISSING, S.A; KAYSER, O.; MULLER, R. H. Solid lipid nanoparticles for parenteral drug delivery. Advanced Drug Delivery Reviews, v.56, p. 1257-1272, 2004. WONG, H. L.; BENDAYAN, R.; RAUTH, A. M.; LI, Y.; WU, X. Y. Chemotherapy with anticancer drugs encapsulated in solid lipid nanoparticles. Advanced Drug Delivery Reviews, v. 59, p. 491–504, 2007. WONG, H. L.; RAUTH, A. M.; BENDAYAN, R.; MANIAS, J. L.; RAMASWAMY,M.; LIU, Z.; ERHAN, S.Z.; WU, X. Y. A New PolymerYLipid Hybrid Nanoparticle System Increases Cytotoxicity of Doxorubicin Against Multidrug-Resistant Human Breast Cancer Cells. Pharmaceutical Research, v. 23, n. 7, 2006. YEGANEH, M. H.; MCLACHLAN, A. J. Determination of terbinafine in tissues. Biomedical Chromatography, v.14, p. 261-268, 2000. YOUENANG PIEMI, M.P.; KORNEV, D.; BENITA, S.; MARTY, J. Positively and negatively charged submicron emulsions for enhanced topical delivery of antifungal drugs. J. Control. Release, v. 58, p.177–187, 1999. YUAN, H.; MIAO, J.; DU, Y-Z.; YOU, J.; HU, F-Q.; ZENG, S. Cellular uptake of solid lipid nanoparticles and cytotoxicity of encapsulated paclitaxel in A549 cancer cells. International Journal of Pharmaceutics, v. 348, p. 137–145, 2008. ZIELONKA, J.;G˛EBICKI, J.; GRYNKIEWICZ, G. Radical scavenging properties of genistein. Free Radic. Biol. Med., v. 35, p. 958–965, 2003.

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