Topology of a ternary complex (proparacaine–β‐cyclodextrin–liposome) by STD NMR

Cabeça, Luis Fernando; Fernandes, Sérgio Antônio; Paula, Eneida de; Marsaioli, Anita Jocelyne

doi:10.1002/mrc.2265

Cited by 22 publications

(27 citation statements)

References 24 publications

(13 reference statements)

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“…In an earlier work, conducted at pH 7, an association constant (K a = 208 M −1 ) has been reported for the 1/2 complex, in good agreement with the values found in this study. [18] Studies conducted for 1/3 revealed a strong association between the charged proparacaine species 1 and p-sulfonic acid calix [6]arene 3 (K a = 5007 M −1 at pH 5) and a diminished association between the uncharged proparacaine 1 and 3 (K a = 11 M −1 ). The results obtained from measurements in an acidic medium (pH 5) show that the protonated proparacaine molecule forms strong complexes with p-sulfonic acid calix [6]arene 3, as opposed to the association of charged 1 with β-CD 2.…”

Section: Resultsmentioning

confidence: 98%

“…[1,2] These carriers protect the loaded drug against degradation, the guest molecule being transported effectively in biological media. [3] The development of such systems include cyclodextrins (CDs), [4 -9] calix[n]arenes, [10 -15] micelles, [16] liposomes, [17,18] micro- [19] and nanoparticles [20] and solid lipid nanoparticles [21 -23] as drug carriers.…”

Section: Introductionmentioning

confidence: 99%

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Proparacaine complexation with β‐cyclodextrin and p‐sulfonic acid calix[6]arene, as evaluated by varied ¹H‐NMR approaches

Arantes

Scarelli

Marsaioli

et al. 2009

Magnetic Reson in Chemistry

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This study focused on the use of NMR techniques as a tool for the investigation of complex formation between proparacaine and cyclodextrins (CDs) or p-sulfonic acid calix[6]arene. The pH dependence of the complexation of proparacaine with beta-CD and p-sulfonic acid calix[6]arene was studied and binding constants were determined by (1)H NMR spectroscopy [diffusion-ordered spectroscopy (DOSY)] for the charged and uncharged forms of the local anesthetic in beta-CD and p-sulfonic acid calix[6]arene. The stoichiometries of the complexes was determined and rotating frame Overhauser enhancement spectroscopy (ROESY) 1D experiments revealed details of the molecular insertion of proparacaine into the beta-CD and p-sulfonic acid calix[6]arene cavities. The results unambiguously demonstrate that pH is an important factor for the development of supramolecular architectures based on beta-CD and p-sulfonic acid calix[6]arene as the host molecules. Such host-guest complexes were investigated in view of their potential use as new therapeutic formulations, designed to increase the bioavailability and/or to decrease the systemic toxicity of proparacaine in anesthesia procedures.

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Section: Resultsmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

Proparacaine complexation with β‐cyclodextrin and p‐sulfonic acid calix[6]arene, as evaluated by varied ¹H‐NMR approaches

Arantes

Scarelli

Marsaioli

et al. 2009

Magnetic Reson in Chemistry

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“…78,79 Alternatively, SUVs could be obtained by homogenization 80 or extrusion 81,82 of an organic suspension of LMVs ( Figure 7). Different phospholipids alone or mixed have been used in different works: egg phosphatidylcholine; 78,81 soy phosphocholine and cholesterol; 79,80 egg phosphatidylcholine, cholesterol, and α-tocopherol; 82,83 and hydrogenated soy phosphatidylcholine and cholesterol.…”

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confidence: 99%

“…Different phospholipids alone or mixed have been used in different works: egg phosphatidylcholine; 78,81 soy phosphocholine and cholesterol; 79,80 egg phosphatidylcholine, cholesterol, and α-tocopherol; 82,83 and hydrogenated soy phosphatidylcholine and cholesterol. 77 In general, drug loading can be done by simply adding the drug to a solution containing the phospholipids, 83,84 or after an extrusion process 81,82 through an ammonium sulfate gradient. 77,79,80 The latter realizes remote loading of the drug in preformed LMVs produced in presence of (NH 4 ) 2 SO 4 .…”

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From micro- to nanostructured implantable device for local anesthetic delivery

Zorzetto

Brambilla

Marcello

et al. 2016

IJN

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Local anesthetics block the transmission of painful stimuli to the brain by acting on ion channels of nociceptor fibers, and find application in the management of acute and chronic pain. Despite the key role they play in modern medicine, their cardio and neurotoxicity (together with their short half-life) stress the need for developing implantable devices for tailored local drug release, with the aim of counterbalancing their side effects and prolonging their pharmacological activity. This review discusses the evolution of the physical forms of local anesthetic delivery systems during the past decades. Depending on the use of different biocompatible materials (degradable polyesters, thermosensitive hydrogels, and liposomes and hydrogels from natural polymers) and manufacturing processes, these systems can be classified as films or micro- or nanostructured devices. We analyze and summarize the production techniques according to this classification, focusing on their relative advantages and disadvantages. The most relevant trend reported in this work highlights the effort of moving from microstructured to nanostructured systems, with the aim of reaching a scale comparable to the biological environment. Improved intracellular penetration compared to microstructured systems, indeed, provides specific drug absorption into the targeted tissue and can lead to an enhancement of its bioavailability and retention time. Nanostructured systems are realized by the modification of existing manufacturing processes (interfacial deposition and nanoprecipitation for degradable polyester particles and high- or low-temperature homogenization for liposomes) or development of novel strategies (electrospun matrices and nanogels). The high surface-to-volume ratio that characterizes nanostructured devices often leads to a burst drug release. This drawback needs to be addressed to fully exploit the advantage of the interaction between the target tissues and the drug: possible strategies could involve specific binding between the drug and the material chosen for the device, and a multiscale approach to reach a tailored, prolonged drug release

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“…Based on our recent results in defining the architecture of drug-macromolecule complexes taking liposomes as membrane models, 8 this paper describes the initial binding events of 1 with the model strain A. tumefaciens NTL4(pZLR4) by saturation transfer difference nuclear magnetic resonance spectroscopy (STD-NMR), identifying the main anchoring sites of 1 and the cell membrane. [9][10][11] The strain A. tumefaciens NTL4(pZLR4) constitutes an interesting model for (acyl-HSL)-cell binding studies since it is unable to produce acyl-HSLs and the experiments would not have interference from self-produced molecules.…”

Section: Introductionmentioning

confidence: 99%

Binding Events of (S)-N-(3-Oxo-octanoyl)-homoserine Lactone with Agrobacterium tumefaciens Mutant Cells Studied by Saturation Transfer Difference NMR

Cabeça¹,

Pomini²,

Cruz³

et al. 2011

J. Braz. Chem. Soc.

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Quorum-sensing é um fenômeno de comunicação amplamente estudado em bactérias, o qual envolve a produção e detecção de substâncias sinalizadoras que dependem do comportamento da colônia e da densidade celular. No presente trabalho, a interação entre a substância sinalizadora (S)-N-(3-oxo-octanoil)-HSL e a membrana celular da A. tumefaciens NTL4(pZLR4) foi estudada utilizando a espectroscopia de RMN da diferença de transferência de saturação (STD-NMR). O mapa do epitopo da substância foi obtido, mostrando que a cadeia hidrofóbica acila apresentou o mais importante ponto de interação. Os resultados foram interpretados em comparação a um sistema modelo de membrana, os lipossomas. Também foi analisado o uso da b-ciclodextrina como carreador da acil-HSL.Quorum-sensing is a widely studied communication phenomenon in bacteria, which involves the production and detection of signaling substances in relation with cell density and colony behavior. Herein, the membrane binding interactions of the signal (S)-N-(3-oxo-octanoyl)-HSL with A. tumefaciens NTL4(pZLR4) cells were studied using saturation transfer difference NMR spectroscopy (STD-NMR). The substance epitope map was obtained showing that the hydrophobic acyl chain is the most important interacting site for the signal and the cell membrane. Results were interpreted upon comparisons with a simpler system, using liposomes as membrane models. Some insights on the use of b-cyclodextrin as acyl-HSL carrier were also provided. Keywords: STD-NMR, acyl-homoserine lactone, membrane interactions IntroductionIt is well recognized nowadays that bacteria use quorum-sensing communication circuits to regulate a wide array of physiological activities. These processes include symbiosis, virulence, competence, conjugation, antibiotic production, motility, sporulation and biofilm formation, among several other phenotypes crucial for bacterial survival and host infection. This phenomenon relies on the production of low molar mass signaling molecules usually related to cell density. In many Gram-negative bacteria the acyl-homoserine lactones (acyl-HSLs) are the most studied chemical signals. 1 In the quorum-sensing process, synthases (LuxI homologs) produce the signaling molecules, which diffuse from the cytoplasm to the near environment through the cellular membrane in the case of short chain acyl-HSLs or through active efflux pumping in long chain ones. 2 The acyl-HSL concentration is related to cell density, i.e., as the colony grows the metabolite concentration also increases due to the presence of new producing individuals. The process continues until a threshold concentration is reached, when the metabolites bind to transcriptional proteins (LuxR homologs) and the complex regulates gene expression. 3 Therefore, quorum-sensing allows whole bacterial populations to act coordinately, improving their chances of successful environment colonization.One of the most interesting quorum-sensing mechanisms was reported for Agrobacterium tumefaciens, a phytopathogen that induces crown gall tu...

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Topology of a ternary complex (proparacaine–β‐cyclodextrin–liposome) by STD NMR

Cited by 22 publications

References 24 publications

Proparacaine complexation with β‐cyclodextrin and p‐sulfonic acid calix[6]arene, as evaluated by varied ¹H‐NMR approaches

Proparacaine complexation with β‐cyclodextrin and p‐sulfonic acid calix[6]arene, as evaluated by varied ¹H‐NMR approaches

From micro- to nanostructured implantable device for local anesthetic delivery

Binding Events of (S)-N-(3-Oxo-octanoyl)-homoserine Lactone with Agrobacterium tumefaciens Mutant Cells Studied by Saturation Transfer Difference NMR

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Topology of a ternary complex (proparacaine–β‐cyclodextrin–liposome) by STD NMR

Cited by 22 publications

References 24 publications

Proparacaine complexation with β‐cyclodextrin and p‐sulfonic acid calix[6]arene, as evaluated by varied 1H‐NMR approaches

Proparacaine complexation with β‐cyclodextrin and p‐sulfonic acid calix[6]arene, as evaluated by varied 1H‐NMR approaches

From micro- to nanostructured implantable device for local anesthetic delivery

Binding Events of (S)-N-(3-Oxo-octanoyl)-homoserine Lactone with Agrobacterium tumefaciens Mutant Cells Studied by Saturation Transfer Difference NMR

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Proparacaine complexation with β‐cyclodextrin and p‐sulfonic acid calix[6]arene, as evaluated by varied ¹H‐NMR approaches

Proparacaine complexation with β‐cyclodextrin and p‐sulfonic acid calix[6]arene, as evaluated by varied ¹H‐NMR approaches