RESUMO
Sulphur-containing volatiles in onion produce unpleasant odors and this limit their usage in foods. To expand its application, several additives including α-cyclodextrin (α-CD), ß-cyclodextrin (ß-CD), 2-hydroxypropyl-ß-cyclodextrin (HP-ß-CD), and chitosan were added to onion solution and evaluated for their effect on sulphur-containing volatiles. Also, antioxidant property using 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay and oxidative stabilities in an oil-in-water (O/W) emulsion were carried out. The total volatile contents were decreased in the order of α-CD (50.1%), ß-CD (49.3%), HP-ß-CD (46.2%), and chitosan (7%). Meanwhile, HP-ß-CD showed the highest DPPH radical scavenging ability followed by ß-CD, α-CD, and chitosan with decreasing order. The ß-CD significantly enhanced the oxidative stability of the O/W emulsion, whereas α-CD and ß-HP-CD showed prooxidative behavior. Overall, ß-CD might be used as a sulphur-containing volatile decreasing agent, which could keep the antioxidant properties of onion in the O/W emulsion.
Assuntos
Quitosana , Ciclodextrinas , Antioxidantes/química , Ciclodextrinas/química , 2-Hidroxipropil-beta-Ciclodextrina/química , Cebolas , Emulsões , SolubilidadeRESUMO
Psoralen (PSO) and 5-methoxypsoralen (5-MOP) are widely used drugs in oral photochemotherapy against vitiligo and major bioactive components of root bark extract of Brosimum gaudichaudii Trécul (EBGT), previously standardized by LC-MS. However, the exceptionally low water solubility of these psoralens can cause incomplete and variable bioavailability limiting their applications and patient adherence to treatment. Therefore, the purpose of this work was to investigate the effects of 2-hydroxypropyl-ß-cyclodextrin (HP-ß-CD) inclusion complex on the solubility and jejunal permeability of PSO and 5-MOP from EBGT. Characterization of inclusion complexes were evaluated by current methods in nuclear magnetic resonance studies on aqueous solution, Fourier transform infrared spectroscopy, thermal analysis, and scanning electron microscopy in solid state. Ex vivo rat jejunal permeability was also investigated and compared for both pure psoralens and plant extract formulation over a wide HP-ß-CD concentration range (2.5 to 70 mM). Phase solubility studies of the PSO- and 5-MOP-HP-ß-CD inclusion complex showed 1:1 inclusion complex formation with small stability constants (Kc < 500 M−1). PSO and 5-MOP permeability rate decreased after adding HP-ß-CD by 6- and 4-fold for pure standards and EBGT markers, respectively. Nevertheless, the complexation with HP-ß-CD significantly improved solubility of PSO (until 10-fold) and 5-MOP (until 31-fold). As a result, the permeability drop could be overcome by solubility augmentation, implying that the HP-ß-CD inclusion complexes with PSO, 5-MOP, or EBGT can be a valuable tool for designing and developing novel oral drug product formulation containing these psoralens for the treatment of vitiligo.
Assuntos
Furocumarinas , Moraceae , Vitiligo , beta-Ciclodextrinas , 2-Hidroxipropil-beta-Ciclodextrina/química , Animais , Varredura Diferencial de Calorimetria , Permeabilidade , Extratos Vegetais/farmacologia , Ratos , Solubilidade , Espectroscopia de Infravermelho com Transformada de Fourier , Difração de Raios X , beta-Ciclodextrinas/químicaRESUMO
Essential oils (EOs) are primarily isolated from medicinal plants and possess various biological properties. However, their low water solubility and volatility substantially limit their application potential. Therefore, the aim of the current study was to improve the solubility and stability of the Mosla Chinensis (M. Chinensis) EO by forming an inclusion complex (IC) with ß-cyclodextrin (ß-CD). Furthermore, the IC formation process was investigated using experimental techniques and molecular modeling. The major components of M. Chinensis 'Jiangxiangru' EOs were carvacrol, thymol, o-cymene, and terpinene, and its IC with ß-CD were prepared using the ultrasonication method. Multivariable optimization was studied using a Plackett-Burman design (step 1, identifying key parameters) followed by a central composite design for optimization of the parameters (step 2, optimizing the key parameters). SEM, FT-IR, TGA, and dissolution experiments were performed to analyze the physicochemical properties of the ICs. In addition, the interaction between EO and ß-CD was further investigated using phase solubility, molecular docking, and molecular simulation studies. The results showed that the optimal encapsulation efficiency and loading capacity of EO in the ICs were 86.17% and 8.92%, respectively. Results of physicochemical properties were different after being encapsulated, indicating that the ICs had been successfully fabricated. Additionally, molecular docking and dynamics simulation showed that ß-CD could encapsulate the EO component (carvacrol) via noncovalent interactions. In conclusion, a comprehensive methodology was developed for determining key parameters under multivariate conditions by utilizing two-step optimization experiments to obtain ICs of EO with ß-CD. Furthermore, molecular modeling was used to study the mechanisms involved in molecular inclusion complexation.
Assuntos
Óleos Voláteis , beta-Ciclodextrinas , Óleos Voláteis/química , Simulação de Acoplamento Molecular , Projetos de Pesquisa , Espectroscopia de Infravermelho com Transformada de Fourier , beta-Ciclodextrinas/química , Solubilidade , Varredura Diferencial de Calorimetria , 2-Hidroxipropil-beta-Ciclodextrina/químicaRESUMO
ß-Carotene is a very important molecule for human health. It finds a large application in the food industry, especially for the development of functional foods and dietary supplements. However, ß-carotene is an unstable compound and is sensitive to light, temperature, and oxygen. To overcome those limitations, various delivery systems were developed. The inclusion of ß-carotene by cyclodextrin aggregates is attractive due to non-toxicity, low hygroscopicity, stability, and the inexpensiveness of cyclodextrins. In this study, ß-carotene/2-hydroxypropyl-ß-cyclodextrin aggregates were prepared based on the procedure of the addition of ß-carotene in an organic solvent to the hot water dispersion of 2-hydroxypropyl-ß-cyclodextrin and the following instant evaporation of the organic solvent. The best conditions for the aggregate preparation were found to be as follows: 25% concentration of 2-hydroxypropyl-ß-cyclodextrin in water, 65 °C temperature, and acetone for ß-carotene dissolution. The efficiency of entrapping was equal to 88%. The procedure is attractive due to the short time of the aggregate preparation.
Assuntos
2-Hidroxipropil-beta-Ciclodextrina/química , beta Caroteno/químicaRESUMO
The active compounds in star anise alcohol extractives (SAAE) have potent bioactivity. However, their poor solubility and stability limit their applications. In this study, SAAE/hydroxypropyl-ß-cyclodextrin (HP-ß-CD) inclusion complexes were prepared as a strategy to overcome the abovementioned disadvantages. The phase solubility results indicated that the solubility of the inclusion complex was enhanced. Complexation was confirmed by complementary methods, including Fourier-transform infrared spectroscopy, nuclear magnetic resonance spectroscopy, scanning electron microscopy, and transmission electron microscopy, which proved to be extremely insightful for studying the inclusion formation phenomenon between SAAE and HP-ß-CD. Despite there being no apparent improvements in the antioxidant capacity and antimicrobial activity, the results of the stability studies presented higher thermal, volatile, and photostability after encapsulation. Further, molecular modeling was used to investigate the factors influencing complex formation and provide the most stable molecular conformation. Thus, based on the obtained results, this study strongly demonstrates the potential of the SAAE/HP-ß-CD inclusion complex in the food industry.
Assuntos
2-Hidroxipropil-beta-Ciclodextrina/química , Illicium/química , Extratos Vegetais/química , 2-Hidroxipropil-beta-Ciclodextrina/análise , Antioxidantes/química , Varredura Diferencial de Calorimetria/métodos , Etanol/química , Espectroscopia de Ressonância Magnética/métodos , Microscopia Eletrônica de Varredura/métodos , Microscopia Eletrônica de Transmissão/métodos , Modelos Moleculares , Extratos Vegetais/análise , Solubilidade , Espectroscopia de Infravermelho com Transformada de Fourier/métodosRESUMO
The purpose of this study was to use hydroxypropyl-ß-cyclodextrin (HP-ß-CD) as a novel carrier in solid SNEDDS and solid dispersions to enhance the solubility and oral bioavailability of poorly water-soluble dexibuprofen. The novel dexibuprofen-loaded solid SNEDDS was composed of dexibuprofen, corn oil, polysorbate 80, Cremophor® EL, and HP-ß-CD at a weight ratio of 45/35/50/15/100. This solid SNEDDS spontaneously formed a nano-emulsion with a size of approximately 120 nm. Unlike the conventional solid SNEDDS prepared with colloidal silica as a carrier, this dexibuprofen-loaded solid SNEDDS exhibited a spherical structure. Similar to the dexibuprofen-loaded solid dispersion prepared with HP-ß-CD, the transformation of the crystalline drug to an amorphous state with no molecular interactions were observed in the solid SNEDDS. Compared to the solid dispersion and dexibuprofen powder, solid SNEDDS significantly enhanced drug solubility and AUC. Therefore, HP-ß-CD is a novel potential carrier in SNEDDS for improving the oral bioavailability of dexibuprofen.
Assuntos
2-Hidroxipropil-beta-Ciclodextrina/química , Portadores de Fármacos/química , Emulsões/química , 2-Hidroxipropil-beta-Ciclodextrina/farmacocinética , Animais , Óleo de Milho/química , Óleo de Milho/farmacocinética , Portadores de Fármacos/farmacocinética , Emulsões/farmacocinética , Glicerol/análogos & derivados , Glicerol/química , Glicerol/farmacocinética , Ibuprofeno/análogos & derivados , Ibuprofeno/química , Ibuprofeno/farmacocinética , Masculino , Polissorbatos/química , Polissorbatos/farmacocinética , Ratos Sprague-Dawley , SolubilidadeRESUMO
Although immuno-oncotherapy in clinic has gained great success, the immunosuppressive tumor microenvironment (TME) existing in the "cold" tumor with insufficient and exhausted lymphocytes may result in a lower-than-expected therapeutic efficiency. Therefore, a properly designed synergistic strategy that can effectively turn the "cold" tumor to "hot" should be considered to improve the therapeutic effects of immuno-oncotherapy. Herein, TME-responsive penetrating nanogels (NGs) were developed, which can improve the delivery and penetration of the co-loaded resiquimod (R848) and green tea catechin (EGCG) in tumors by a nano-sized controlled releasing system of the soluble cyclodextrin-drug inclusion complex. Consequently, the NGs effectively promoted the maturation of dendritic cells, stimulated the cytotoxic T lymphocytes (CTLs), and decreased the PD-L1 expression in tumors. The combination of NGs with the OX40 agonist (αOX40) further synergistically enhanced the activation and infiltration of CTLs into the deep tumor and inhibited the suppression effects from the regulatory T cells (Tregs). As a result, an increased ratio of active CTLs to Tregs in tumors (20.66-fold) was achieved with a 91.56% tumor suppression effect, indicating a successful switch of "cold" tumors to "hot" for an immunologically beneficial TME with significantly improved anti-tumor immune therapeutics. This strategy could be tailored to other immuno-oncotherapeutic approaches to solve the urgent efficiency concerns of the checkpoint-based treatment in clinic.
Assuntos
Antineoplásicos/uso terapêutico , Catequina/uso terapêutico , Portadores de Fármacos/química , Imidazóis/uso terapêutico , Nanogéis/química , Neoplasias/tratamento farmacológico , 2-Hidroxipropil-beta-Ciclodextrina/química , Animais , Antineoplásicos/química , Antineoplásicos/farmacocinética , Antígeno B7-H1/metabolismo , Catequina/química , Catequina/farmacocinética , Linhagem Celular Tumoral , Células Dendríticas/efeitos dos fármacos , Portadores de Fármacos/farmacocinética , Liberação Controlada de Fármacos , Feminino , Ácido Hialurônico/análogos & derivados , Imidazóis/química , Imidazóis/farmacocinética , Imunomodulação , Camundongos Endogâmicos C57BL , Neoplasias/metabolismo , Linfócitos T Citotóxicos/efeitos dos fármacos , Linfócitos T Reguladores/efeitos dos fármacos , Microambiente Tumoral/efeitos dos fármacosRESUMO
Mesenchymal stem cells are increasingly studied for their use as drug-carrier in addition to their intrinsic potential for regenerative medicine. They could be used to transport molecules with a poor bioavailability such as curcumin in order to improve their clinical usage. This natural polyphenol, well-known for its antioxidant and anti-inflammatory properties, has a poor solubility that limits its clinical potential. For this purpose, the use of NDS27, a curcumin salt complexed with hydroxypropyl-beta-cyclodextrin (HPßCD), displaying an increased solubility in aqueous solution, is preferred. This study aims to evaluate the uptake of NDS27 into skeletal muscle-derived mesenchymal stem cells (mdMSCs) and the effects of such uptake onto their mesenchymal properties. It appeared that the uptake of NDS27 into mdMSCs is concentration-dependent and not time-dependent. The use of a concentration of 7 µmol/L which does not affect the viability and proliferation also allows preservation of their adhesion, invasion and T cell immunomodulatory abilities.
Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Diferenciação Celular , Curcumina/farmacologia , Células-Tronco Mesenquimais/citologia , Músculo Esquelético/citologia , 2-Hidroxipropil-beta-Ciclodextrina/química , Animais , Anti-Inflamatórios não Esteroides/química , Terapia Baseada em Transplante de Células e Tecidos , Células Cultivadas , Curcumina/química , Portadores de Fármacos/química , Cavalos , Células-Tronco Mesenquimais/efeitos dos fármacos , Músculo Esquelético/efeitos dos fármacosRESUMO
The aim of this study is to prepare composite films incorporated with star anise ethanol extract (SAEE)/hydroxypropyl-ß-cyclodextrin (HP-ß-CD) inclusion complex. The effects of sodium alginate concentration on mechanical properties of films are tested. Sodium alginate, SAEE, and SAEE/HP-ß-CD inclusion complex-based composite films are characterized in terms of UV-visible spectroscopy, microstructure characterizations, including transmission electron microscopy, scanning electronic microscopy, Fourier transform infrared, and 1 H NMR analysis, and molecular modeling calculations. With various stoichiometries, the complexes of sodium alginate/SAEE/HP-ß-CD are compared through both theoretical and experimental analyses. Molecular simulations are applied to predict the possible orientations of SAEE inside the HP-ß-CD cavity and the optimal stoichiometry of the complex formation. According to the simulation, the system of sodium alginate/SAEE (or SAEE/HP-ß-CD inclusion complex) in a 3:1 stoichiometry reaches the lowest total energy and achieves a balance in complex system. In addition, the composite films can maintain high-content vitamin C and reduce weight loss rate of fresh-cut Chinese yam. In conclusion, coinciding with the experimental results, the molecular modeling successfully calculates the reasonable molecular structure and molecular behavior of sodium alginate/SAEE/HP-ß-CD inclusion complex. The composite films in this study have the potential to be used for food packaging applications. PRACTICAL APPLICATION: In this paper, we present composite films incorporated with star anise ethanol extract (SAEE)/hydroxypropyl-ß-cyclodextrin (HP-ß-CD) inclusion complex for the use of fresh-cut Chinese yam preservation. The present study demonstrates a successful application of molecular modeling to predict the geometry of the final complex. It can serve as a powerful tool to calculate the energy of association between inclusion complex and sodium alginate molecules.
Assuntos
2-Hidroxipropil-beta-Ciclodextrina , Alginatos , Embalagem de Alimentos/instrumentação , Illicium/química , Extratos Vegetais , 2-Hidroxipropil-beta-Ciclodextrina/química , Alginatos/análise , Alginatos/química , Varredura Diferencial de Calorimetria , Dioscorea , Etanol , Estrutura Molecular , Extratos Vegetais/química , SolubilidadeRESUMO
Curcumin (CUR) has antioxidant and anti-inflammatory effects that are beneficial to Alzheimer's disease (AD). However, the poor solubility and high instability of CUR compromise its application greatly. In this study, CUR-encapsulated chitosan-coated poly (lactic-co-glycolic acid) nanoparticles (CUR-CS-PLGA-NPs) and hydroxypropyl-ß-cyclodextrin-encapsulated CUR complexes (CUR/HP-ß-CD inclusion complexes) were developed and compared through intranasal administration. In vitro studies indicated that CUR in CUR/HP-ß-CD inclusion complexes was stable under physiological conditions over 72 h with 95.41 ± 0.01% remaining, which was higher than 49.66 ± 3.91% remaining in CUR-CS-PLGA-NPs. Meanwhile, CUR/HP-ß-CD inclusion complexes showed a higher cellular uptake level of CUR than CUR-CS-PLGA-NPs in SH-SY5Y cells. Both formulations could reduce CUR's cellular cytotoxicity and showed a comparable antioxidant effect. Both formulations displayed the anti-inflammatory effect at 20 µM CUR in BV-2 cells, which decreased TNF-α and IL-6 levels to approximately 70 and 40%, respectively, when compared to the positive control, respectively. In vivo pharmacokinetic studies indicated that after intranasal administration, the AUC values of CUR in the plasma and brain of the CUR/HP-ß-CD inclusion complex group were 2.57-fold and 1.12-fold higher than those in the CUR-CS-PLGA-NP group at the same dose of 2 mg/kg, respectively. In conclusion, CUR/HP-ß-CD inclusion complexes displayed better properties than CUR-CS-PLGA-NPs as a carrier for intranasal delivery of CUR for application in AD.
Assuntos
2-Hidroxipropil-beta-Ciclodextrina/química , Doença de Alzheimer/tratamento farmacológico , Anti-Inflamatórios/administração & dosagem , Antioxidantes/administração & dosagem , Quitosana/química , Curcumina/administração & dosagem , Portadores de Fármacos/química , Nanopartículas/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Administração Intranasal , Animais , Anti-Inflamatórios/farmacocinética , Antioxidantes/farmacocinética , Linhagem Celular Tumoral , Curcumina/farmacocinética , Composição de Medicamentos/métodos , Estabilidade de Medicamentos , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , SolubilidadeRESUMO
The nutraceutical system of curcumin-piperine in 2-hydroxypropyl-ß-cyclodextrin was prepared by using the kneading technique. Interactions between the components of the system were defined by X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC), infrared spectroscopy (FT-IR), nuclear magnetic resonance (NMR). Application of hydroxypropyl-ß-cyclodextrin as a carrier-solubiliser improved solubility of the curcumin-piperine system, its permeability through biological membranes (gastrointestinal tract, blood-brain barrier) as well as the antioxidant, antimicrobial and enzyme inhibitory activities against acetylcholinesterase and butyrylcholinesterase.
Assuntos
2-Hidroxipropil-beta-Ciclodextrina/química , Acetilcolinesterase/metabolismo , Alcaloides/química , Benzodioxóis/química , Butirilcolinesterase/metabolismo , Inibidores da Colinesterase/química , Curcumina/química , Portadores de Fármacos/química , Piperidinas/química , Alcamidas Poli-Insaturadas/química , Alcaloides/farmacologia , Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Antioxidantes/química , Antioxidantes/farmacologia , Benzodioxóis/farmacologia , Transporte Biológico , Barreira Hematoencefálica/metabolismo , Inibidores da Colinesterase/farmacologia , Curcumina/farmacologia , Suplementos Nutricionais , Composição de Medicamentos , Trato Gastrointestinal/metabolismo , Humanos , Piperidinas/farmacologia , Alcamidas Poli-Insaturadas/farmacologia , SolubilidadeRESUMO
Acidic environments, such as in inflamed tissues, favor the charged form of local anesthetics (LA). Hence, these drugs show less cell permeation and diminished potency. Since the analgesic capsaicin (CAP) triggers opening of the TRPV1 receptor pore, its combination with LAs could result in better uptake and improved anesthesia. We tested the above hypothesis and report here for the first time the analgesia effect of a two-drug combination (LA and CAP) on an inflamed tissue. First, CAP solubility increased up to 20 times with hydroxypropyl-beta-cyclodextrin (HP-ß-CD), as shown by the phase solubility study. The resulting complex (HP-ß-CD-CAP) showed 1:1 stoichiometry and high association constant, according to phase-solubility diagrams and isothermal titration calorimetry data. The inclusion complex formation was also confirmed and characterized by differential scanning calorimetry (DSC), X-ray diffraction, and 1H-NMR. The freeze-dried complex showed physicochemical stability for at least 12 months. To test in vivo performance, we used a pain model based on mouse paw edema. Results showed that 2% mepivacaine injection failed to anesthetize mice inflamed paw, but its combination with complexed CAP resulted in pain control up to 45 min. These promising results encourages deeper research of CAP as an adjuvant for anesthesia in inflamed tissues and cyclodextrin as a solubilizing agent for targeting molecules in drug delivery.
Assuntos
2-Hidroxipropil-beta-Ciclodextrina/química , Anestesia Local/métodos , Anestésicos Locais/uso terapêutico , Capsaicina/uso terapêutico , Composição de Medicamentos/métodos , Excipientes/química , Hiperalgesia/tratamento farmacológico , Mepivacaína/uso terapêutico , Dor/tratamento farmacológico , Animais , Varredura Diferencial de Calorimetria , Capsaicina/química , Carragenina/efeitos adversos , Modelos Animais de Doenças , Estabilidade de Medicamentos , Quimioterapia Combinada , Hiperalgesia/induzido quimicamente , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Espectroscopia de Ressonância Magnética , Masculino , Camundongos , Microscopia Eletrônica de Varredura , Manejo da Dor/métodos , Solubilidade , Difração de Raios XRESUMO
Two structural isomeric pentacyclic triterpenes, oleanolic acid and ursolic acid, were considered as the models for the quality control of many traditional Chinese herbal medicines and they have been proved to own important pharmacological activities. In the present work, liquid chromatographic and liquid-liquid chromatographic separation with high peak resolution of structural isomeric oleanolic acid and ursolic acid using hydroxypropyl-ß-cyclodextrin as mobile phase additive was successfully achieved, respectively. A high peak resolution, RS=8.143, was achieved for the two structural isomeric compounds by conventional reverse phase high performance liquid chromatography, which was greatly improved compared with the published values. Meanwhile, a biphasic solvent system composed of n-hexane-ethyl acetate-0.1 mol/L hydroxypropyl-ß-cyclodextrin (9:1:10, v/v) was selected for liquid-liquid chromatography, which provided a high peak resolution, RS = 6.573, for analytical apparatus and Rs = 8.500 for semi-preparative apparatus after optimization by liquid-liquid extractions. Two elution modes including reverse phase mode and normal phase mode were investigated for preparative separation of two acids from crude exact of Eriobotrya japonica Thunb. Furthermore, the inclusion complex between each of the two structural isomers and hydroxypropyl-ß-cyclodextrin were also investigated for high performance liquid chromatography and liquid-liquid chromatography, respectively, in which formation constants were determined for oleanolic acid and ursolic acid.
Assuntos
2-Hidroxipropil-beta-Ciclodextrina/química , Cromatografia Líquida/métodos , Ácido Oleanólico/química , Ácido Oleanólico/isolamento & purificação , Triterpenos/química , Triterpenos/isolamento & purificação , Cromatografia de Fase Reversa , Eriobotrya/química , Isomerismo , Solventes , Temperatura , Termodinâmica , beta-Ciclodextrinas/química , Ácido UrsólicoRESUMO
Pulmonary fibrosis (PF) is a kind of interstitial lung disease with the features of progressive and often fatal dyspnea. Tetrandrine (TET) is the major active constituent of Chinese herbal Stephania tetrandra S. Moore, which has already applied clinically to treat rheumatism, lung cancer, and silicosis. In this work, a tetrandrine-hydroxypropyl-ß-cyclodextrin inclusion compound (TET-HP-ß-CD) was developed for the treatment of pulmonary fibrosis via inhalation administration. TET-HP-ß-CD was prepared by the freeze-drying method and identified using the cascade impactor, differential scanning calorimetry (DSC), X-ray diffraction (XRD), and Fourier transform infrared spectrum (FT-IR). A bleomycin-induced pulmonary fibrosis rat model was used to assess the effects of inhaled TET and TET-HP-ß-CD. Animal survival, hydroxyproline content in the lungs, and lung histology were detected. The results showed that inhalation of TET-HP-ß-CD alleviated inflammation and fibrosis, limited the accumulation of hydroxyproline in the lungs, regulated protein expression in PF development, and improved postoperative survival. Moreover, nebulized delivery of TET-HP-ß-CD accumulated chiefly in the lungs and limited systemic distribution compared with intravenous administration. The present results indicated that inhalation of TET-HP-ß-CD is an attractive candidate for the treatment of pulmonary fibrosis.
Assuntos
2-Hidroxipropil-beta-Ciclodextrina/química , Benzilisoquinolinas/química , Fibrose Pulmonar/tratamento farmacológico , 2-Hidroxipropil-beta-Ciclodextrina/administração & dosagem , 2-Hidroxipropil-beta-Ciclodextrina/farmacocinética , Administração por Inalação , Animais , Benzilisoquinolinas/administração & dosagem , Benzilisoquinolinas/farmacocinética , Modelos Animais de Doenças , Pulmão/metabolismo , Pulmão/patologia , Masculino , Fibrose Pulmonar/mortalidade , Fibrose Pulmonar/patologia , Ratos , Ratos Sprague-Dawley , Solubilidade , Espectroscopia de Infravermelho com Transformada de Fourier , Fator de Necrose Tumoral alfa/análiseRESUMO
The purpose of this study was to prepare and characterize inclusion complexes between tea polyphenol (TP) and hydroxypropyl-ß-cyclodextrin (HP-ß-CD), and to evaluate their antioxidant properties. Freeze-drying was used to prepare the inclusion complex of TP/HP-ß-CD at different component ratios (1:0.5, 1:1, and 1:2). The supermolecular structure of the TP/HP-ß-CD complex was characterized by Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), and scanning electron microscopy (SEM). Molecular docking was used to simulate the positions and interactions of the binding sites of TP/HP-ß-CD inclusion complexes and target protein receptors. In addition, the effects of TP/HP-ß-CD inclusion complexes on myofibrillar protein (MP) from lamb tripe were observed under oxidative conditions. Results showed that TP was encapsulated in the cavity of HP-ß-CD to form an optimal complex with 1:2 molar ratio of stoichiometry, while the FTIR, TGA, and SEM studies also support the inclusion process. Molecular modeling results were systematically analyzed to determine the stability of inclusion complexes and protein. Furthermore, the addition of an appropriate concentration (5 to 105 µmol/g) of TP/HP-ß-CD inclusion complex decreased the carbonyl content, hydrophobicity, and protein aggregation of MP from lamb tripe, whereas it increased the sulfhydryl content. This improved antioxidant activity and bioavailability of the inclusion complexes will be beneficial for its potential applications in food. PRACTICAL APPLICATION: Tea polyphenol was an antioxidant with potential for the field of food. In this study, the unstable properties of tea polyphenols were evaluated and were improved by inclusion of HP-ß-cyclodextrin. The binding mode of the inclusion complex with protein was revealed via the molecular docking method, and the application of inclusion complex to control protein oxidation was studied. Results showed that the inclusion complex could effectively inhibit protein oxidation, which can provide a reference for the application of polyphenols in meat products and the improvement of protein properties.
Assuntos
2-Hidroxipropil-beta-Ciclodextrina/química , Antioxidantes/química , Extratos Vegetais/química , Polifenóis/química , Animais , Disponibilidade Biológica , Varredura Diferencial de Calorimetria , Camellia sinensis/química , Liofilização , Interações Hidrofóbicas e Hidrofílicas , Microscopia Eletrônica de Varredura , Simulação de Acoplamento Molecular , Ovinos , Espectroscopia de Infravermelho com Transformada de FourierRESUMO
The development of inclusion complexes is used to encapsulate nonpolar compounds and improve their physicochemical characteristics. This study aims to develop complexes made up of Euterpe oleracea Mart oil (EOO) and ß-cyclodextrin (ß-CD) or hydroxypropyl-ß-cyclodextrin (HP-ß-CD) by either kneading (KND) or slurry (SL). Complexes were analyzed by molecular modeling, Fourier-transform infrared spectroscopy, scanning electron microscopy, powder X-ray diffraction, thermogravimetry analysis and differential scanning calorimetry. The antibacterial activity was expressed as Minimum Inhibitory Concentration (MIC), and the antibiotic resistance modulatory activity as subinhibitory concentration (MIC/8) against Escherichia coli, Streptomyces aureus, Pseudomonas aeruginosa and Enterococcus faecalis. Inclusion complexes with ß-CD and HP-ß-CD were confirmed, and efficiency was proven by an interaction energy between oleic acid and ß-CD of -41.28 ± 0.57 kJ/mol. MIC values revealed higher antibacterial activity of complexes compared to the isolated oil. The modulatory response of EOO and EOO-ß-CD prepared by KND as well as of EOO-ß-CD and EOO-HP-ß-CD prepared by SL showed a synergistic effect with ampicillin against E. coli, whereas it was not significant with the other drugs tested, maintaining the biological response of antibiotics. The antimicrobial response exhibited by the complexes is of great significance because it subsidizes studies for the development of new pharmaceutical forms.
Assuntos
2-Hidroxipropil-beta-Ciclodextrina/farmacologia , Antibacterianos/farmacologia , Euterpe/química , Óleos de Plantas/química , beta-Ciclodextrinas/farmacologia , 2-Hidroxipropil-beta-Ciclodextrina/química , Ampicilina/farmacologia , Antibacterianos/química , Farmacorresistência Bacteriana/efeitos dos fármacos , Sinergismo Farmacológico , Enterococcus faecalis/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Pseudomonas aeruginosa/efeitos dos fármacos , Streptomyces/efeitos dos fármacos , beta-Ciclodextrinas/químicaRESUMO
ß-Cyclodextrin- and 2-hydroxypropyl-ß-cyclodextrin/Danube common nase (Chondrostoma nasus L.) oil complexes (ß-CD- and HP-ß-CD/CNO) have been obtained for the first time. The fatty acid (FA) profile of the CNO indicates an important content of polyunsaturated fatty acids, the most important being eicosapentaenoic acid (EPA, 6.3%) and docosahexaenoic acid (DHA, 1.6%), both ω-3 FAs. The complexes have been obtained by kneading method. The moisture content and successful of molecular encapsulation have been evaluated by thermal and spectroscopic techniques. Thermogravimetry and differential scanning calorimetry analyses reveals that the moisture content of CD/CNO complexes significantly decreased, compared to starting CDs. On the other hand, the crystallinity index was for the first time determined for such type of complexes, the ß-CD/CNO complex having values of 43.9(±18.3)%, according to X-ray diffractometry. FA profile and CD/CNO characteristics sustain the use of these ω-3 based complexes for food supplements or functional food products, but further studies are needed.
Assuntos
2-Hidroxipropil-beta-Ciclodextrina/química , Óleos de Peixe/química , beta-Ciclodextrinas/química , Animais , Varredura Diferencial de Calorimetria , Cyprinidae , Solubilidade , Difração de Raios XRESUMO
Grape seed extract (GSE) displays strong antioxidant activity, but its instability creates barriers to its applications. Herein, three HP-ß-CD/GSE inclusion complexes with host-guest ratios of 1:0.5, 1:1, and 1:2 were successfully prepared by co-precipitation method to improve stability. Successful embedding of GSE in the HP-ß-CD cavity was confirmed by fourier-transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), differential scanning calorimetry (DSC), and scanning electron microscopy (SEM) analyses. The Autodock Tools 1.5.6 was used to simulate the three-dimensional supramolecular structure of the inclusion complex of 2-hydroxypropyl-ß-cyclodextrin and grape seed extract (HP-ß-CD/GSE) by molecular docking. The MALDI-TOF-MS technology and chemical database Pubchem, and structural database PDB were combined to reconstitute the three-dimensional structure of target protein. The binding mode of the HP-ß-CD/GSE inclusion complex to target protein was studied at the molecular level, and the antioxidant ability of the resulting HP-ß-CD/GSE inclusion complexes was investigated by measuring 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging. The effects of HP-ß-CD/GSE on myofibrillar protein from lamb tripe were also investigated under oxidative conditions. The positions and interactions of the binding sites of HP-ß-CD/GSE inclusion complexes and target protein receptors were simulated by molecular docking. The results showed that HP-ß-CD/GSE inclusion complexes were successfully prepared, optimally at a molar ratio of 1:2. At low (5 µmol/g) to medium (105 µmol/g) concentrations, HP-ß-CD/GSE inclusion complexes decreased the carbonyl content, hydrophobicity, and protein aggregation of myofibrillar protein from lamb tripe, and increased the sulphydryl content. Furthermore, high concentration (155 µmol/g) of HP-ß-CD/GSE inclusion complexes promoted protein oxidation.
Assuntos
2-Hidroxipropil-beta-Ciclodextrina/farmacologia , Antioxidantes/farmacologia , Extrato de Sementes de Uva/farmacologia , Estresse Oxidativo/efeitos dos fármacos , 2-Hidroxipropil-beta-Ciclodextrina/química , Animais , Antioxidantes/química , Compostos de Bifenilo/farmacologia , Varredura Diferencial de Calorimetria , Extrato de Sementes de Uva/química , Microscopia Eletrônica de Varredura , Miofibrilas/efeitos dos fármacos , Oxirredução/efeitos dos fármacos , Estresse Oxidativo/genética , Picratos/farmacologia , Polifenóis/química , Polifenóis/farmacologia , Agregação Patológica de Proteínas/genética , Agregação Patológica de Proteínas/prevenção & controle , Ovinos , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Espectroscopia de Infravermelho com Transformada de Fourier , Difração de Raios XRESUMO
The chroman-like chalcone Xanthohumol C, originally found in hops, was demonstrated to be a potent neuroregenerative and neuroprotective natural product and therefore constitutes a strong candidate for further pharmaceutical research. The bottleneck for in vivo experiments is the low water solubility of this chalcone. Consequently, we developed and validated a suitable formulation enabling in vivo administration. Cyclodextrins were used as water-soluble and nontoxic complexing agents, and the complex of Xanthohumol C and 2-hydroxypropyl-ß-cyclodextrin was characterized using HPLC, HPLC-MS, NMR, and differential scanning calorimetry. The water solubility of Xanthohumol C increases with increasing concentrations of cyclodextrin. Using 50 mM 2-hydroxypropyl-ß-cyclodextrin, solubility was increased 650-fold. Furthermore, in vitro bioactivity of Xanthohumol C in free and complexed form did not significantly differ, suggesting the release of Xanthohumol C from 2-hydroxypropyl-ß-cyclodextrin. Finally, a small-scaled in vivo experiment in a rat model showed that after i.âp. administration of the complex, Xanthohumol C can be detected in serum, the brain, and the cerebrospinal fluid at 1 and 6 h post-administration. Mean (± SD) Xanthohumol C serum concentrations after 1, 6, and 12 h were determined as 463.5 (± 120.9), 61.9 (± 13.4), and 9.3 (± 0.8) ng/mL upon i.âv., and 294.3 (± 22.4), 45.5 (± 0.7), and 13 (± 1.0) ng/mL after i.âp. application, respectively. Accordingly, the formulation of Xanthohumol C/2-hydroxypropyl-ß-cyclodextrin is suitable for further in vivo experiments and further pharmaceutical research aiming for the determination of its neuroregenerative potential in animal disease models.
Assuntos
2-Hidroxipropil-beta-Ciclodextrina/administração & dosagem , Benzopiranos/administração & dosagem , 2-Hidroxipropil-beta-Ciclodextrina/química , 2-Hidroxipropil-beta-Ciclodextrina/farmacocinética , Animais , Benzopiranos/química , Benzopiranos/farmacocinética , Disponibilidade Biológica , Varredura Diferencial de Calorimetria , Cromatografia Líquida de Alta Pressão , Estabilidade de Medicamentos , Espectroscopia de Ressonância Magnética , Ratos , SolubilidadeRESUMO
Reverse micelles (RMs) with confined water pools have been applied in many fields. However, the water insolubility of RMs seriously limits the scope of their application, especially those needed to operate in aqueous environments. Here, we report the first successful transfer of RMs from the organic phase to water phase without disturbing their confined water pools and hydrophobic alkyl region. This transfer was achieved by virtue of a mild host-guest interaction between the hydrophobic tails of interfacial cross-linked reverse micelles (ICRMs) and the hydrophobic cavity of (2-hydroxypropyl)-ß-cyclodextrin (HP-ß-CD). Benefitting from the maintained confined water pools and the hydrophobic scaffold, the obtained water-soluble ICRMs served as multifunctional nanoplatforms for enzyme-mimicking catalysis and image-guided cancer therapy, which were impossible for normal RMs lacking water solubility or confined pool-buried water-soluble nanoparticles without a hydrophobic alkyl chain. This mild transfer approach thus surmounts the application obstacle of RMs and opens up new avenues for their application in aqueous environments.