Biblioteca Digital

The equilibrium of meso-tetrakis(4-N-methylpyridiniumyl)porphyrin (TMPyP) in aqueous solution in the presence of surfactants was studied by optical spectroscopic techniques and SAXS (small angle X-ray scattering). Anionic SDS (sodium dodecyl sulfate), zwitterionic HPS (N-hexadecyl-N,N-dimethyl-3-ammonio-1-propanesulfonate) and nonionic TRITON X-100 (t-octyl-phenoxypolyethoxyethanol), surfactants were used. TMPyP is characterized by a protonation equilibrium with a pK(a) around 1.0, associated with the diacid-free base transition, and a second pK(a) around 12.0 related with the transition between the free base and the monoanion form. Three independent species were observed for TMPyP at pH 6.0 as a function of SDS concentration: free TMPyP, TMPyP-SDS aggregates and porphyrin monomer bound to micelles. For HPS and TRITON X-100, the equilibrium of TMPyP as a function of pH is quite similar to that obtained in pure aqueous solution: no aggregation was observed, suggesting that electrostatic contribution is the major factor in the interaction between TMPyP and surfactants. SAXS data analysis demonstrated a prolate ellipsoidal shape for SDS micelles; no significant changes in shape and size were observed for SDS-TMPyP co-micelles. Moreover...

Interfacial concentrations of chloride and bromide ions, with Li+, Na+, K+, Rb+, Cs+, trimethylammonium (TMA(+)), Ca2+, and Mg2+ as counterions, were determined by chemical trapping in micelles formed by two zwitterionic surfactants, namely N-hexadecyl-N,N-dimethyl-3-ammonio-1-propanesulfonate (HPS) and hexadecylphosphorylcholine (HDPC) micelles. Appropriate standard curves for the chemical trapping method were obtained by measuring the product yields of chloride and bromide salts with 2,4,6-trimethyl-benzenediazonium (BF4) in the presence of low molecular analogs (N,N,N-trimethyl-propane sulfonate and methyl-phosphorylcholine) of the employed surfactants. The experimentally determined values for the local Br- (Cl-) concentrations were modeled by fully integrated non-linear Poisson Boltzmann equations. The best fits to all experimental data were obtained by considering that ions at the interface are not fixed at an adsorption site but are free to move in the interfacial plane. In addition, the calculation of ion distribution allowed the estimation of the degree of ion coverage by using standard chemical potential differences accounting for ion specificity. (C) 2012 Elsevier Inc. All rights reserved.; Fundacao de Amparo a Pesquisa do Estado de Sao Paulo...

Addition of salts, especially perchlorates, to zwitterionic micelles of SB3-14, C(14)H(29)NMe(2)(+)(CH(2))(3)SO(3)(-), induces anionic character and uptake of H(3)O(+) by SB3-14 micelles. Thus, the addition of alkali metal perchlorates accelerates the acid hydrolysis of 2-(p-heptoxypheny1)-1,3-dioxolane, HPD, in the presence of SB3-14 micelles, which depends on the local proton concentration at the micelle surface. The addition of metal chlorides to solutions of such perchlorate-modified SB3-14 micelles decreases both the negative zeta potential of the micelles and the observed rate constant for acid hydrolysis of HPD. The effect of the monovalent cations Li(+), Na(+), and K(+) is smaller than that of the divalent cations Be(2+), Mg(2+), and Ca(2+), and much smaller than that of the trivalent cations Al(3+), La(3+), and Er(3+). The major factor responsible for this cation valence dependence of these effects is shown to be electrostatic in nature, reflecting the strong dependence of the micellar surface potential on the cation valence. The fact that the salt effects are not identical after correction for the electrostatic effects indicates that additional secondary nonelectrostatic effects may contribute as well.; Conselho Nacional do Desenvolvimento Cientifico e Tecnologico (CNPq...

Photosensitizers (PS) photodynamic activities are regulated by their location in the biological target, which modulates their photophysical and photochemical features. In this work the PS partition for the Xanthene Dyes Fluorescein (FSC), Eosin Y(EOS), Erythrosin B (ERY) and Rose Bengal B (RBB) in biomimetic models (SDS, CTAB and Pluronic P-123 micelles) and the effects on their photophysical characteristics are evaluated. The hydrophobic and electrostatic forces that govern the PS-micelle interaction are analyzed. At physiological pH (7.25), the ability of the dianionic protolytic form of the dyes to be positioned into the micelle palisade and its micelle interaction depends not only on the hydrophobicity of the dye but also on the micellar surface charge. The Binding Constants obey exactly the same order of the Partition Coefficients for the dyes in P-123 and CTAB micelles. The Stern-Volmer treatment pointed out that dyes are located inside the micelle, especially ERY and RBB. The magnitude of the dye-micelle interaction increased from SDS, P-123 and finally CTAB micelles due to the charges between dye and micelle, and among the xanthenes, their hydrophobic characteristics. Within the micelle pseudo phase, ERY and RBB are still very efficient photosensitizers exhibiting high quantum yield of singlet oxygen...

Micelles composed of amphiphilic copolymers linked to a radioactive element are used in nuclear medicine predominantly as a diagnostic application. A relevant advantage of polymeric micelles in aqueous solution is their resulting particle size, which can vary from 10 to 100 nm in diameter. In this review, polymeric micelles labeled with radioisotopes including technetium (99mTc) and indium (111In), and their clinical applications for several diagnostic techniques, such as single photon emission computed tomography (SPECT), gamma-scintigraphy, and nuclear magnetic resonance (NMR), were discussed. Also, micelle use primarily for the diagnosis of lymphatic ducts and sentinel lymph nodes received special attention. Notably, the employment of these diagnostic techniques can be considered a significant tool for functionally exploring body systems as well as investigating molecular pathways involved in the disease process. The use of molecular modeling methodologies and computer-aided drug design strategies can also yield valuable information for the rational design and development of novel radiopharmaceuticals.

Membranas e organelas constituem estruturas presentes nas células dos organismos. Estas estruturas representam interfaces entre eletrólitos. Uma tentativa de descrever, interpretar e compreender a distribuição iônica nas vizinhanças destas estruturas é feita neste trabalho com a análise de resultados de experimentos obtidos na investigação de alguns sistemas: 1) Sistemas constituídos por micelas de SDS. Medidas do pH nas vizinhanças de superfícies das micelas por sondas derivadas do ácido salicílico mostra variações do pH em termos da concentração de SDS e da concentração de sal adicionado. O objetivo dos experimentos é inferir o comportamento do pH nas vizinhanças de membranas biológicas que, por dissociação de alguns fosfolipídios, podem apresentar segmentos da membrana com carga na superfície. 2) A natureza "zwitteriônica" das membranas biológicas motivou o estudo da "ligação iônica" em micelas "zwitteriônicas", imersas em soluções com eletrólito, em concentrações variadas de sais de Cl- e Br- com os cátions monovalentes, Li+, Na+, K+, Rb+, Cs+ e tetrametil amônio (TMA+) e bivalentes Mg2+ e Ca2+. Os experimentos consistiram em determinar a concentração de haletos próximos a micela. A técnica de captura química mostra que há um grau de seletividade que não é determinado apenas pela carga iônica. 3) Resultados preliminares do grau de dissociação no interior de vesiculas de...

O interesse por sistemas formados por misturas de surfatantes se deve ao fato destas misturas apresentarem propriedades diferentes, e algumas vezes superiores, às dos surfatantes puros. Neste trabalho foram realizadas, em água e em soluções aquosas de sal, medidas de CMC, constantes de dissociação iônica, concentrações superficiais de contra-íons e entalpias de micelização para misturas de surfatantes zwiteriônicos e catiônicos. Os surfactantes catiônicos utilizados foram: brometo e cloreto de N- hexadecil - N,N,N - trimetil amônio, CTAB(C), e brometo de N- dodecil N,N,N - trimetil amônio, DTAB. Os zwiteriônicos foram: N-hexadecil- N,N-dimetil-3-amônio-1-propanosulfonato, HPS, e N-dodecil- N,N-dimetil-3amônio-1-propanosulfonato, DPS, e n-hexadecil- fosforil colina, HFC. Medidas de tensão superficial, condutividade e entalpia molar de diluição em função da concentração da mistura mostraram que, em água, ocorre primeiro a formação de micelas zwiteriônicas, seguida, com o aumento da concentração total de detergente, da incorporação do surfatante catiônico na fase micelar. A adição de sal facilita a formação de micelas mistas, principalmente nas misturas formadas por surfatantes de maior cadeia hidrocarbônica. Em micelas mistas medidas da concentração superficial de contra-íons por captura química mostraram que a concentração superficial de contra-íons aumenta com a fração molar do detergente catiônico. A concentração superficial de ânions é maior para misturas HPS/CT AB do que para misturas H FC/CTAB...

Micelas são agregados coloidais formados por moléculas anfifílicas i.e., moléculas com uma região hidrofóbica e uma porção hidrofílica (surfactantes). Efeitos específicos de íons (EEIs) são observados em micelas iônicas, uma vez que as propriedades físico-químicas de agregado micelares, como tamanho e geometria, dependem da natureza do contra-íon. Diferentes ânions inorgânicos produzem alterações modestas nas propriedades de agregados micelares catiônicos, mas ânions orgânicos podem induzir efeitos mais pronunciados, como transições de forma do agregado ou separações de fase. Em sistemas micelares, os EEIs podem estar relacionados a: (a) diferenças na localização dos ânions nas micelas; (b) diferenças na hidratação micellar e de íons; e (c) possível formação de pares iônicos entre surfactantes e contra-íons na interface micelar. Diversos modelos foram desenvolvidos para descrever a formação e estabilidade de agregados micelares, considerando diferentes termos energéticos que possivelmente contribuem para a formação/estabilidade de micelas. Contudo, os termos descritos acima (a - c) geralmente não são incluídos nos modelos micelares. Assim, não deve ser possível predizer as propriedades de micelas catiônicas...

Purpose: This paper focuses on the characterization of polymeric micelle-forming tuberculostatic prodrugs and the antimycobacterial activity of these prodrugs.Method: By the condensation of hydroxymethylpyrazinamide, isoniazid and rifampin with free carboxyl groups on the copolymer poly(ethyleneglycol)-poly(aspartic acid), micelle-forming carrier-drug conjugates were obtained. These micelles were characterized by dynamic light scattering, to measure the micelle diameter; by acid-base titration, to determine the percentage of carboxylic groups occupied by the tuberculostatic; by Sudan III solubility tests, to estimate the critical micelle concentration (CMC); and visual control and spectrophotometric measurement, to determine the stability of micelles. These micelles were tested in vitro against several Mycobacterium strains.Results: As expected, the size and distribution of the micelle-forming tuberculostatic prodrugs found to be small (78.2nm, 84.2nm and 98.9 nm) while the level of the drug conjugated was high (65.02-85.7%). Furthermore, the micelles were stable in vitro, exhibiting a low level of CMC and stronger antimycobacterial activity than the original drugs.Conclusion: the results demonstrate that polymeric micelles can be used as efficient carriers for drugs...

A formação, estabilidade e aplicações das micelas gigantes têm sido amplamente estudadas. Estes sistemas são muito interessantes devido ao seu comportamento reológico similar aos polímeros. Porém, as micelas gigantes são espécies supramoleculares mantidas por ligações não-covalentes, portanto, sob alta turbulência, podem resistir à degradação mecânica, além de promoverem redução de atrito hidrodinâmico devido ao efeito Toms. Neste estudo, a formação e estabilidade das micelas gigantes formadas pela combinação de surfatantes catiônicos e diferentes compostos aromáticos, foram estudadas sistematicamente. A redução de atrito foi observada medindo o torque aplicado à solução para manter a turbulência. A temperatura do sistema foi progressivamente aumentada, mostrando o ponto específico em que as micelas gigantes são termicamente destruídas. Baseado neste estudo foi possível estabelecer a ordem em termos de estabilidade: ácido orto-hidróxicinâmico (OHCA) ~ salicilato > tosilato > ácido orto-metóxi-cinâmico (OMCA) > fenol. Para benzoato e metóxibenzoato não foi observada a formação de micelas gigantes. Estes resultados revelam algumas interações peculiares entre a cabeça do surfatante e a molécula aromática. Em regimes semidiluídos...

Biochemical and Biophysical Research Communications 308 (2003) 73–78; We report the kinetic behavior of the enzyme aldehyde oxidoreductase (AOR) from the sulfate reducing bacterium Desulfovibrio gigas (Dg) encapsulated in reverse micelles of sodium bis-(2-ethylhexyl) sulfosuccinate in isooctane using benzaldehyde, octaldehyde, and decylaldehyde as substrates. Dg AOR is a 200-kDa homodimeric protein that catalyzes the conversion of aldehydes to carboxylic acids. Ultrasedimentation analysis of Dg AOR-containing micelles showed the presence of 100-kDa molecular weight species, confirming that the Dg AOR subunits can be dissociated. UV–visible spectra of encapsulated Dg AOR are indistinguishable from the enzyme spectrum in solution, suggesting that both protein fold and metal cofactor are kept intact upon encapsulation. The catalytic constant (kcat) profile as a function of the micelle size W0 (W0 ¼ ½H2O /[AOT]) using benzaldehyde as substrate showed two bell-shaped activity peaks at W0 ¼ 20 and 26. Furthermore, enzymatic activity for octaldehyde and decylaldehyde was detected only in reverse micelles. Like for the benzaldehyde kinetics, two peaks with both similar kcat values and W0 positions were obtained. EPR studies using spin-labeled reverse micelles indicated that octaldehyde and benzaldehyde are intercalated in the micelle membrane. This suggests that...

The alkaline hydrolysis of curcumin was studied in three types of micelles composed of the cationic surfactants cetyl trimethylammonium bromide (CTAB) and dodecyl trimethylammonium bromide (DTAB) and the anionic surfactant sodium dodecyl sulfate (SDS). At pH 13, curcumin undergoes rapid degradation by alkaline hydrolysis in the SDS micellar solution. In contrast, alkaline hydrolysis of curcumin is greatly suppressed in the presence of either CTAB or DTAB micelles, with a yield of suppression close to 90%. The results from fluorescence spectroscopic studies reveal that while curcumin remains encapsulated in CTAB and DTAB micelles at pH 13, curcumin is dissociated from the SDS micelles to the aqueous phase at this pH. The absence of encapsulation and stabilization in the SDS micellar solution results in rapid hydrolysis of curcumin.; Mandy H. M. Leung, Hannah Colangelo and Tak W. Kee; Copyright © 2008 American Chemical Society

Femtosecond fluorescence upconversion experiments were performed on the naturally occurring medicinal pigment, curcumin, in anionic, cationic, and neutral micelles. In our studies, the micelles are composed of sodium dodecyl sulfate (SDS), dodecyl trimethyl ammonium bromide (DTAB), and triton X-100 (TX-100). We demonstrate that the excited-state kinetics of curcumin in micelles have a fast (3-8 ps) and slow (50-80 ps) component. While deuteration of curcumin has a negligible effect on the fast component, the slow component exhibits a pronounced isotope effect of approximately 1.6, indicating that micelle-captured curcumin undergoes excited-state intramolecular hydrogen atom transfer. Studies of solvation dynamics of curcumin in a 10 ps time window reveal a fast component (< or = 300 fs) followed by a 8, 6, and 3 ps component in the solvation correlation function for the TX-100, DTAB, and SDS micelles, respectively.; Ramkrishna Adhikary, Philip J. Carlson, Tak W. Kee and Jacob W. Petrich

The use of conventional therapy based on a single therapeutic agent is not optimal to treat human diseases. The concept called "combination therapy", based on simultaneous administration of multiple therapeutics is recognized as a more efficient solution. Interestingly, this concept has been in use since ancient times in traditional herbal remedies with drug combinations, despite mechanisms of these therapeutics not fully comprehended by scientists. This idea has been recently re-enacted in modern scenarios with the introduction of polymeric micelles loaded with several drugs as multidrug nanocarriers. This Concept article presents current research and developments on the application of polymeric micelles for multidrug delivery and combination therapy. The principles of micelle formation, their structure, and the developments and concept of multidrug delivery are introduced, followed by discussion on recent advances of multidrug delivery concepts directed towards targeted drug delivery and cancer, gene, and RNA therapies. The advantages of various polymeric micelles designed for different applications, and new developments combined with diagnostics and imaging are elucidated. A compilation work from our group based on multidrug-loaded micelles as carriers in drug-releasing implants for local delivery systems based on titania nanotubes is summarized. Finally...

A química supramolecular envolve estruturas mantidas por interações intermoleculares. Neste contexto, sistemas que apresentam estruturas auto organizadas são de interesse devido importância como ciência de base bem como aplicabilidade. Neste trabalho foram utilizadas micelas de brometo de hexadeciltrimetilamônio (CTAB) como reticulantes de hidroxietilceluloses hidrofobicamente modificadas. Como as micelas estão em constante quebra e recombinação, reticulações transientes são obtidas. Tais sistemas apresentam comportamento reológico característico, dependente da concentração do surfactante. Obervou-se que a celulose que apresenta maior ramificação hidrofóbica resulta em aumento mais efetivo da viscosidade como consequência do maior grau de reticulação. A Técnica de calorimetria de titulação isotérmica (ITC) foi utilizada de modo a compreender os processos energéticos envolvidos na agregação. Com esta pôde-se obter parâmetros do sistema como cmc, cac e ?H°mic . Elucidou-se também que as interações polímero-surfactante são de origem hidrofóbica. A adição de salicilato de sódio (NaSal) em solução de CTAB leva a formação de micelas gigantes. Determinou-se por ITC a razão, [CTAB]/[NaSal], em que ocorre a formação de micelas gigantes...

Le cancer est la principale cause de mortalité au Canada. Les taxanes (e.g. le paclitaxel et le docétaxel (DCTX)) constituent des remèdes efficaces contre une série de tumeurs solides telles que les cancers du sein, du poumon et de l’ovaire. Par ailleurs, des acides nucléiques (e.g. les oligonucléotides antisens (AON) ou les petits ARN interférents (siRNAs)), capables de supprimer sélectivement certains oncogènes impliqués dans la carcinogénèse, sont actuellement étudiés pour traiter une large gamme de cancers. Bien que l’activité des taxanes et des acides nucléiques soit bien établie sur des modèles humains et/ou animaux, plusieurs aspects physico-chimiques et cliniques restent encore à améliorer. Leur solubilité limitée (pour les taxanes), leur dégradation rapide dans le sang (pour les acides nucléiques), leur élimination précoce, leur absence de sélectivité et leur toxicité envers les tissus sains sont les principaux facteurs limitant leur efficacité. C’est pourquoi de nombreux efforts ont porté sur l’élaboration de systèmes de vectorisation ciblés à base de polymères, dans le but de surmonter les problèmes associés aux thérapies actuelles. Dans cette thèse, deux types de micelles polymères ont été développés pour la vectorisation de DCTX et d’acides nucléiques. D’une part...

Les micelles polyioniques ont émergé comme des systèmes prometteurs de relargage de médicaments hydrophiles ioniques. Le but de cette étude était le développement des micelles polyioniques à base de dextrane pour la relargage de médicaments hydrophiles cationiques utilisant une nouvelle famille de copolymères bloc carboxymethyldextran-poly(éthylène glycol) (CMD-PEG). Quatre copolymères CMD-PEG ont été préparés dont deux copolymères identiques en termes de longueurs des blocs de CMD et de PEG mais différent en termes de densité de charges du bloc CMD; et deux autres copolymères dans lesquels les blocs chargés sont les mêmes mais dont les blocs de PEG sont différents. Les propriétés d’encapsulation des micelles CMD-PEG ont été évaluées avec différentes molécules cationiques: le diminazène (DIM), un médicament cationique modèle, le chlorhydrate de minocycline (MH), un analogue semi-synthétique de la tétracycline avec des propriétés neuro-protectives prometteuses et différents antibiotiques aminoglycosidiques. La cytotoxicité des copolymères CMD-PEG a été évaluée sur différentes lignées cellulaires en utilisant le test MTT et le test du Bleu Alamar. La formation de micelles des copolymères de CMD-PEG a été caractérisée par différentes techniques telles que la spectroscopie RMN 1H...

A consideração explicita de troca iônica em soluções micelas conduz a expressões gerais que contém somente termos experimentalmente acessíveis. Estas expressões servem como marco de referência geral para a análise do efeito de micelas em reações que envolvem íons. As expressões incluem: a ligação de um íon reativo a micela na presença ou ausência de sal, a reação monomolecular de um substrato iônico na fase micelar, a reação bimolecular de um nucleófilo iônico na fase micelar e o efeito de micelas na dissociação de ácidos fracos e as suas consequências cinéticas. Estas expressões foram utilizadas para analisar quantitativamente a hidrólise alcalina de acetato de p-nitrofenila em tampão. Uma das predições do modelo, um mínimo no pK aparente de um ácido fraco na presença de micelas foi confirmado estudando o efeito de brometo de hexadeciltrimetilamônio na dissociação de n-heptilmercaptana e fenol. O efeito de sais no pK do fenol na presença de micelas, também predito pelo modelo, foi analisado quantitativamente.; The explicit consideration of specific ion exchange leads to general expressions which contain experirmentally accessible terms. These expressions serve as an unified conceptual framework for the quantitative dissection and analysis of the influence of charged interfaces on reactions which involve such specifically-bound ionic species. These include the binding of a reactive ion to the micelle in the presence ar absence of salt...

We investigated the intranasal administration of poly(ethylene oxide)–poly(propylene oxide) polymeric micelles loaded with high payloads of the first-line antiretroviral drug efavirenz for targeting to the CNS. The effect of micellar size and composition and drug payload was assessed, employing simple micelles made of a highly hydrophilic copolymer, poloxamer F127, loaded with 20 mg/ml drug and mixed micelles containing 75% of a medium hydrophobic poloxamine, T904, and 25% F127 loaded with 20 and 30 mg/ml drug, respectively. F127 confers high physical stability, while T904 substantially improves the encapsulation capacity of the micelles. The bioavailability of the drug in the CNS was increased fourfold and the relative exposure index (ratio between the area-under-the-curve in the CNS and plasma) was increased fivefold with respect to the same system administered intravenously. These findings demonstrate the potential of this scalable and cost-viable strategy to attack the HIV sanctuary in the CNS.; Fil: Chiappetta, Diego Andrés. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Tecnología Farmacéutica; Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina;; Fil: Hocht...

Artículo de publicación ISI; The solubilization sites provided by micelles formed by a diblock copolymer with one neutral hydrophobic block, polystyrene, and one charged hydrophilic block, poly(acrylic acid) or poly(methacrylic acid), have been studied by fluorescence quenching of pyrene by polar and nonpolar quenchers. Pyrene solubilized into these micelles is distributed between the inner corona and the micelle core. The fraction of pyrene residing in the inner corona is almost unity for star micelles, where the corona-forming blocks are larger than the core-forming blocks, and around 0.5 for crew-cut micelles where the opposite situation prevails. The kinetics of the quenching process depends on the pyrene location, i.e. is static in the micelle core, and largely dynamic in the inner corona at low quencher concentration. The rate constants for fluorescence quenching by nitromethane are shown to increase with increasing pH.; FONDECYT grant 1070371 and The Royal Society.