Complexação de guaiacol com ß-ciclodextrina para tratamento de alveolite seca: avaliação in vitro e in vivo / ß-cyclodextrin complexation of guaiacol for the treatment of dry socket: in vitro and in vivo evaluation

A alveolite seca (AS) é uma das complicações pós-operatórias mais comuns e sintomáticas na odontologia, porém, até o momento não há um protocolo de tratamento definido. O composto fenólico guaiacol (Gu) é um dos materiais utilizados para revestimento intra-alveolar devido às suas propriedades analgésicas, antioxidantes e antimicrobianas. Contudo, sua desvantagem é a dificuldade de manipulação decorrente da sua baixa estabilidade, alta volatilidade e sensibilidade à oxidação. Para melhorar suas propriedades e aumentar sua aplicabilidade clínica, um complexo de inclusão de Gu com ß-ciclodextrina (ßcd) foi desenvolvido. A formação do complexo supramolecular de Gu:ßcd foi caracterizada mediante a ressonância magnética nuclear (RMN), nos experimentos de 1H e 2D ROESY. A atividade antibacteriana do Gu e Gu:ßcd frente a Escherichia coli, Staphylococcus aureus, Streptococcus mitis, Streptococcus mutans, Streptococcus sanguis e Aggregatibacter actinomycetemcomitans foi analisada pelo método da microdiluição e sua citotoxicidade em osteoblastos de calvária de rato, foi estudado com o ensaio do MTT. O processo de reparo alveolar induzido pelo Gu:ßcd foi avaliado histologicamente após tratamento de alveolite seca em molares inferiores de ratos. A RMN mostrou correlações espaciais entre os hidrogênios internos (H3 e H5) da ßcd e os hidrogênios aromáticos, H(a) e H(b) do Gu, confirmando a formação do complexo. A complexação do Gu na ßcd potencializou seu efeito antibacteriano e reduziu sua citotoxicidade em osteoblastos. O estudo in vivo evidenciou a ocorrência de ossificação no ápice alveolar dos ratos tratados com Gu:ßcd, no 7o dia. No 14o dia, as trabéculas ósseas ocuparam também o terço médio do alvéolo e no 21o dia, todo o alvéolo se encontrava preenchido por osso neoformado. Estes resultados foram similares ao controle negativo e superiores ao controle positivo (Alvogyl®). Os benefícios obtidos pela inclusão do Gu na ßcd foram demonstrados pela melhora das...

Dry socket is one of the most common and symptomatic complications in dentistry, however, there is still not a settled treatment for this condition. The phenolic compound guaiacol (Gu) is one of several alveolar dressings used in dry socket because it has analgesic, antioxidant and antimicrobial properties. Nevertheless, its disadvantage is the difficulty of manipulation due to its low stability, high volatility and sensitivity to oxidation. To improve its properties and increase its clinical applicability, an inclusion complex of Gu with ß-cyclodextrin (ßcd) was developed. The Gu:ßcd supramolecular complex was characterized by Nuclear Magnetic Ressonance (NMR), in the 1H and 2D ROESY experiments. The antibacterial activity of Gu and Gu:ßcd over Escherichia coli, Staphylococcus aureus, Streptococcus mitis, Streptococcus mutans, Streptococcus sanguis and Aggregatibacter actinomycetemcomitans was analyzed using the microdilution method and its cytotoxicity in rat calvaria-derived osteoblast was evaluated with the MTT assay. The alveolus repair process induced by Gu:ßcd was histologically studied after the treatment of dry socket in rat mandibular molars. The NMR showed spatial correlations between internal hydrogens (H3 and H5) of ßcd and aromatic hydrogens, H(a) and H(b), of Gu confirming the inclusion complex formation. Gu:ßcd complex potentiated Gu antibacterial effect and reduced its cytotoxicity in osteoblasts. The in vivo study revealed that ossification occurred in the alveolar apex of rats treated with Gu:ßcd, by day 7. In the 14th day, the trabecular bone occupied the apical and middle thirds of the socket and on the 21st day, the entire alveolus was filled by newly formed bone. These results were similar to the negative control and superior to the positive control (AlvogylTM). Benefits gained from inclusion of Gu in cyclodextrin have been particularly demonstrated by the improvement in Gu biological properties in vitro and the appropriate alveolus...

Efeito preventivo e terapêutico de cárie de nanocompostos de ciclodextrinas e TiF4: estudo in vitro / Preventive and therapeutic effect of caries of nanocomplexes formed of cyclodextrins and TIF4: in vitro study

Os objetivos do presente trabalho in vitro foram analisar se as inclusões de TiF4 a hidroxipropil-ß-CD (HP-ß-CD) ou gama-ciclodextrina (γ-CD) nos diferentes tempos de agitação/complexação (12 ou 72 horas) inibem a desmineralização do esmalte hígido (estudo 1) e investigar se a inclusão do tetrafluoreto de titânio (TiF4) à beta ciclodextrina (ßCD) com 72 horas de agitação remineraliza o esmalte previamente desmineralizado (estudo 2). Para o estudo 1, noventa e seis blocos foram selecionados pela microdureza superficial e aleatoriamente alocados nos seguintes grupos (n=12 cada): G1: Água Mili-Q, G2: HP-ß-CD 1%, G3: γ-CD 1%, G4: TiF4 1%, G5: HP-ß-CD associada ao TiF4 1% com 12 horas de agitação, G6: γ-CD associada ao TiF4 1% com 12 horas de agitação, G7: HP-ß-CD associada ao TiF4 1% com 72 horas de complexação e G8: γ-CD associada ao TiF4 1% com 72 horas de complexação. Para o estudo 2, quarenta e oito blocos (previamente desmineralizados) foram alocados em 4 grupos (n=12 cada) da seguinte maneira: controle (água Mili-Q), solução ß-CD 1%, solução TiF4 1% e TiF4:ß-CD. Todas as soluções foram aplicadas uma única vez na superfície do esmalte com o microbrush por um minuto e submetidos a ciclagem de pH (37º C) por 8 dias mais 24 horas na solução remineralizante. A variável resposta para o estudo 1 foi o percentual de perda de microdureza superficial (%PMS). Para o estudo 2, foram %PMS e microdureza transversal (MT).. Em ambos estudos, os blocos foram avaliados pela microscopia eletrônica de varredura e pela espectrometria de energia dispersiva de raios-X (EDX). Os achados foram avaliados pelo ANOVA e Tukey (p-valor < 0,05). Para o primeiro objetivo, G1 não diferiu estatisticamente de G2 e G3 (p>0.05). G5 produziu menor %PMS comparado a G1 (p<0,01), G2 (p<0,01), G3 (p<0,01), G7 (p=0,03) e G8 (p=0,01), sem diferença estatística para o G4 e G6. Eles não diferiram de nenhum dos grupos, mas foram inferiores a G5. Para o segundo objetivo, na superfície, todos os grupos foram capazes de promover a remineralização do esmalte sem diferença estatística entre eles (p>0,05). Na MT, nenhum grupo diferiu do controle, mas TiF4:ß-CD foi estatisticamente superior (p=0,03) comparado ao TiF4. Os blocos tratados com TiF4 e TiF4:CD apresentaram camada de TiO2 e na avaliação do EDX o titânio foi detectado nos grupos de TiF4 e TiF4:CD apenas na superfície. Conclui-se que a solução de HP-ß-CD: TiF4 com 12 horas de complexação demonstrou significativa habilidade em reduzir a desmineralização superficial do esmalte hígido e a solução de TiF4:ß-CD com 72 horas de agitação foi superior a solução do TiF4 em remineralizar a subsuperfície do esmalte. (AU)

The aims of the present in vitro study were to evaluate if the titanium tetrafluoride (TiF4) inclusions to hydroxypropyl-ß-CD (HP-ß-CD) and gamma-cyclodextrin (γ-CD) with different periods of stirring (12 or 72 hours) reduce demineralization of sound enamel (study 1) and to assess if the inclusion of titanium tetrafluoride (TiF4) to beta-cyclodextrin (ß-CD) with 72 hours of stirring remineralize previously demineralized enamel blocks (study 2). For study 1, ninety six blocks were selected by surface microhardness and randomly allocated in the following groups (n=12 each) G1: Mili-Q water, G2: 1% HP-ß-CD, G3: 1% γ-CD, G4: 1% TiF4, G5: HP-ß-CD associated with 1% TiF4 at 12 hours of complexation, G6: γ-CD associated with 1% TiF4 at 12 hours of complexation, G7: HP-ß-CD connected to 1% TiF4 at 72 hours of complexation and G8: γ-CD connected to 1% TiF4 at 72 hours of complexation. For study 2, forty eight enamel blocks (previously demineralized) were allocated in 4 groups (n=12 each) as follows: control (Mili-Q water), solution of 1% ß-CD, solution of 1% TiF4 and solution TiF4:ß-CD. All solutions were applied once over enamel surface with a microbrush for one minute and the submitted to pH-cycling regimen (37º C) for 8 days plus 24 hours on remineralizing solution. For study 1, the response variable was percentage of surface microhardness change (%SMC). For study 2, %SMC and cross-sectional microhardness (CSMH) were assessed. The enamel blocks were evaluated by scanning electron microscopy and energy dispersive spectrometry (EDX) for both studies. Findings were tested using ANOVA and Tukey (p-value < 0.05). For the first aim, G1 did not differ statistically from G2 and G3 (p>0.05). G5 produced less %SMC when compared to G1 (p<0.01), G2 (p<0.01), G3 (p<0.01), G7 (p=0.03) and G8 (p=0.01), although no statistical difference was observed compared to G4 and G6. G4 and G6 were not different from any of the groups, but were inferior to G5. For the second aim, all groups were able to promote rehardening of enamel surface without statistical difference between them (p> 0.05). In cross-sectional microhardness, no group differed from the control, but TiF4:ß-CD was statistically superior (p = 0.03) compared to TiF4. The slabs treated with TiF4 and TiF4:CD groups showed TiO2 glaze-layer and the EDX evaluation identified titanium in TiF4 and TiF4:CD groups only on the surface.In conclusion, the solution containing the inclusion complex of HP-ß-CD: TiF4 at 12 hours of complexation period demonstrated significant ability to reduce the surface demineralization of sound enamel and the solution containing TiF4 and ß-cyclodextrin inclusion complex was superior than the TiF4 solution itself on rehardening enamel subsurface. (AU

Chiral recognition of functionalized cyclodextrins in capillary electrophoresis.

The chiral recognition of hydroxypropylated, dimethylated, and sulfated cyclodextrins was evaluated by utilizing them as chiral additives in capillary electrophoresis. Although each selector yielded enantiomeric separations of most of the target analytes, differences were observed in the electrophoretic results for the different derivatized cyclodextrins and for additives having varying degrees of substitution. The results for the sulfated cyclodextrins also highlighted the importance of knowing the degree of substitution as well as the location of the substituents when comparing chiral selectors.

Enantioseparation of linear and cyclic chiral bis(phenethyl)amines by means of cyclodextrin-modified capillary electrophoresis.

For two years drugs introduced to the market have had- to be enantiomerically pure. Rapid and cheap methods of high reproducibility must, therefore, be available for evaluation of enantiomeric purity. Within the framework of a larger project dealing with chiral recognition of phenethylamines by means of native and derivatized cyclodextrins it was intended to find capillary electrophoresis methods suitable for separation of the enantiomers of chiral bis(phenethyl)amines and their corresponding cyclic analogues, within 10 min, using small amounts of a chiral selector, to save time and money. Heptakis(2,3-O-diacetyl-6-sulfato)beta-CD was found to be the most promising candidate most often fulfilling these requirements.

Quantitative determination of alpha-cyclodextrin in human plasma by liquid chromatography/positive ion electrospray mass spectrometry.

A sensitive and selective method for the determination of alpha-cyclodextrin in human plasma is described using beta-cyclodextrin as an internal standard. After protein precipitation with perchloric acid, the analytes were isolated from human plasma by solid-phase extraction on Bond Elut C18 cartridges. The compounds were chromatographed on a narrow-bore aminopropyl column (125 x 2 mm i.d., 5 microm) and analyzed by electrospray ionization mass spectrometry in the positive selected-ion mode using the [M+NH4]+ ion. The lower limit of quantitation was 5 ng ml(-1) of human plasma. Linear calibration curves were obtained over the concentration range 5-1000 ng ml(-1) of human plasma. The intra- and inter-assay precisions were <18% and the accuracy was <10.5% over the entire concentration range. During the method development, the ionization efficiencies of the analytes in plasma samples originating from different sources were examined to overcome the matrix effect problems caused by co-eluting endogenous compounds. The method was successfully applied to pharmacokinetic studies in human volunteers.