Suchergebnisse

Halloysite nanotubes are becoming interesting materials for drug delivery. The knowledge of surface interactions is important for optimizing this application. The aim of this work is to perform a computational study of the interaction between 5-aminosalicylic acid (5-ASA) drug and halloysite nanotubes for the development of modified drug delivery systems. The optimization of this nanotube and the adsorption of different conformers of the 5-ASA drug on the internal surface of halloysite in the presence and absence of water were performed using quantum mechanical calculations by using Density Functional Theory (DFT) and methods based on atomistic force fields for molecular modeling, respectively. ; Authors are thankful to Helio Anderson Duarte for providing atomic coordinates of a slice of halloysite and César Viseras for their fruitful discussions, and to the CSIC Computational Center for computation facilities. This work is funded by the Andalusian Government projects (RNM1897) and the MINECO project FIS2016-77692-C2-2P. It also supported by the Egyptian Cultural Affairs and Missions Sector (Plan 2013-2014), Ministry of Higher Education. M.E.A. is especially thankful to the Egyptian Cultural Affairs and Missions Sector, Mahmoud Mohamed El Rahmany, and Mahmoud Hassaan El-Basha (Faculty of Science, Al-Azhar University in Cairo), for their encouragements and fruitful discussions.

The adsorption of retinol, niacinamide and glycolic acid active ingredients on the internal surface of halloysite in an aqueous environment was explored at the molecular level by means of calculations based on quantum mechanics and force fields from empirical interatomic potentials. These active ingredients are stably adsorbed on the internal surface of halloysite forming hydrogen bonds between the hydrogen, oxygen and nitrogen atoms with the hydroxyl groups of the inner surface of the halloysite. In addition, electrostatic interaction between these active ingredients with the water molecules was observed. Therefore, the theoretical results indicate that the adsorption of these active principles is favourable in the halloysite nanotube, which allows directing future experimental investigations for the development and design of retinol, niacinamide and glycolic acid with halloysite nanotubes systems, which may be topical formulations for skincare. ; This research was funded by Spanish Ministerio de Economía, Industría y Competitividad, grant number PCIN2017-098, and by Regional Government Junta de Andalucía with FEDER European contribution, grant number P18-RT-3786.

Halloysite nanotubes are becoming interesting materials for drug delivery. The knowledge of surface interactions is important for optimizing this application. The aim of this work is to perform a computational study of the interaction between 5-aminosalicylic acid (5-ASA) drug and halloysite nanotubes for the development of modified drug delivery systems. The optimization of this nanotube and the adsorption of different conformers of the 5-ASA drug on the internal surface of halloysite in the presence and absence of water were performed using quantum mechanical calculations by using Density Functional Theory (DFT) and methods based on atomistic force fields for molecular modeling, respectively. ; This work is funded by the Andalusian Government projects (RNM1897) and the MINECO project FIS2016-77692-C2-2P. It also supported by the Egyptian Cultural Affairs and Missions Sector (Plan 2013-2014), Ministry of Higher Education.

Inorganic hydrogels formulated with spring waters and clay minerals are used to treat musculoskeletal disorders and skin a ections. Their underlying mechanism of action for skin disorders is not clear, although it is usually ascribed to the chemical composition of the formulation. The aim of this study was to assess the composition and in vitro release of elements with potential wound healing e ects from hydrogels prepared with two nanoclays and natural spring water. In vitro Franz cell studies were used and the element concentration was measured by inductively coupled plasma techniques. Biocompatibility studies were used to evaluate the potential toxicity of the formulation against fibroblasts. The studied hydrogels released elements with known therapeutic interest in wound healing. The released ratios of some elements, such as Mg:Ca or Zn:Ca, played a significant role in the final therapeutic activity of the formulation. In particular, the proliferative activity of fibroblasts was ascribed to the release of Mn and the Zn:Ca ratio. Moreover, the importance of formulative studies is highlighted, since it is the optimal combination of the correct ingredients that makes a formulation e ective. ; Instituto de Salud Carlos III Spanish Government CGL2016-80833-R ; Junta de Andalucía P18-RT-3786 ; Ministerio de Educación, Cultura y Deporte FPU15/01577

This research was funded by Spanish Ministerio de Economia, Industria y Competitividad, grant number PCIN2017-098, and by Regional Government Junta de Andalucia with FEDER European contribution, grant number P18-RT-3786. ; The adsorption of retinol, niacinamide and glycolic acid active ingredients on the internal surface of halloysite in an aqueous environment was explored at the molecular level by means of calculations based on quantum mechanics and force fields from empirical interatomic potentials. These active ingredients are stably adsorbed on the internal surface of halloysite forming hydrogen bonds between the hydrogen, oxygen and nitrogen atoms with the hydroxyl groups of the inner surface of the halloysite. In addition, electrostatic interaction between these active ingredients with the water molecules was observed. Therefore, the theoretical results indicate that the adsorption of these active principles is favourable in the halloysite nanotube, which allows directing future experimental investigations for the development and design of retinol, niacinamide and glycolic acid with halloysite nanotubes systems, which may be topical formulations for skincare. ; Spanish Ministerio de Economia, Industria y Competitividad PCIN2017-098 ; Junta de Andalucia ; European Commission P18-RT-3786

Praziquantel is an antiparasitic drug indicated for the treatment of the schistosomiasis disease. This drug has very low aqueous solubility, requiring high oral doses for its administration which gives rise to side effects, therapeutic noncompliance and the appearance of resistant forms of the parasite. Clay minerals, like sepiolite and montmorillonite, are innocuous, non-toxic, biocompatible and low-cost excipients. Additionally, clays have high adsorbent properties that allow them to encapsulate drugs in nanometric spaces present in the channels in the case of the sepiolite or between the layers in the case of the montmorillonite. The interactions between the drug and clay minerals are studied experimentally with the strategy for preparing interactions products in organic solvents (ethanol, acetonitrile and dichloromethane) so that the interaction will be more effective and will be enhanced the aqueous solubility of praziquantel. The results showed that in the interaction products, the drug interacted with both clay minerals, which produced the loss of the crystallinity of the drug demonstrated by different techniques. This led to a significant increase in the dissolution rate of the praziquantel in all the interaction products in the simulated gastrointestinal tract media, except for the praziquantel¿montmorillonite product prepared in dichloromethane that presented a controlled release in acid medium. Moreover, in vitro cytotoxicity and cell cycle studies were performed in the interaction products prepared with ethanol. The interaction product with sepiolite was biocompatible with the HTC116 line cells, and it did not produce alterations in the cell cycle. However, interaction products with montmorillonite did not produce cell death, but they showed affectation and damage of cells in the cell cycle study at the highest concentration tested (20¿100 µM). Therefore, the different organic solvents used are adequate for the improvement of the biopharmaceutical profile of praziquantel. Drug¿clay interaction products, specifically with sepiolite, showed very promising results in which new accelerated oral release systems of the praziquantel were obtained ; This research was funded by Ministerio de Ciencia e Innovación government, grants numbers PCIN-2017-098, FIS2016-77692-C2-2-P and CGL2016-80833-R and by Consejería de Economía, Innovación, Ciencia y Empleo, Junta de Andalucía government, grants numbers RNM1897 and P18-RT-3786.

This work aimed at studying the potentiality of interactions between kaolinite surfaces and a protein-fragment (350–370 amino acid units) extracted from the glycoprotein E1 in the transmembrane domain (TMD) of hepatitis C virus capsid. A computational work was performed for locating the potential electrostatic interaction sites between kaolinite aluminol and siloxane surfaces and the residues of this protein-fragment ligand, monitoring the possible conformational changes. This hydrated neutralized kaolinite/protein-fragment system was simulated by means of molecular modeling based on atomistic force fields based on empirical interatomic potentials and molecular dynamic (MD) simulations. The MD calculations indicated that the studied protein-fragment interacted with the kaolinite surfaces with an exothermic process and structural distortions were observed, particularly with the hydrophilic aluminol surface by favorable adsorption energy. The viral units isolation or trapping by the adsorption on the kaolinite nanoparticles producing structural distortion of the peptide ligands could lead to the blockage of the entry on the receptor and hence a lack of viral activity would be produced. Therefore, these findings with the proposed insights could be an useful information for the next experimental and development studies in the area of discovering inhibitors of the global challenged hepatitis and other pathogenic viruses based on the phyllosilicate surface activity. These MD studies can be extended to other viruses like the COVID-19 interacting with silicate minerals surfaces. ; Authors would like to acknowledge the contribution of the European COST Action CA17120 supported by the EU Framework Program Horizon 2020 and the financial support of the Andalusia Government projects [RNM1897 and RNM363, and CTS-946]; the MINECO and FEDER projects [FIS2016-77692-C2-2-P, PCIN-2017-098]. ; Peer reviewed

Praziquantel is an antiparasitic drug indicated for the treatment of the schistosomiasis disease. This drug has very low aqueous solubility, requiring high oral doses for its administration which gives rise to side effects, therapeutic noncompliance and the appearance of resistant forms of the parasite. Clay minerals, like sepiolite and montmorillonite, are innocuous, non-toxic, biocompatible and low-cost excipients. Additionally, clays have high adsorbent properties that allow them to encapsulate drugs in nanometric spaces present in the channels in the case of the sepiolite or between the layers in the case of the montmorillonite. The interactions between the drug and clay minerals are studied experimentally with the strategy for preparing interactions products in organic solvents (ethanol, acetonitrile and dichloromethane) so that the interaction will be more effective and will be enhanced the aqueous solubility of praziquantel. The results showed that in the interaction products, the drug interacted with both clay minerals, which produced the loss of the crystallinity of the drug demonstrated by different techniques. This led to a significant increase in the dissolution rate of the praziquantel in all the interaction products in the simulated gastrointestinal tract media, except for the praziquantel–montmorillonite product prepared in dichloromethane that presented a controlled release in acid medium. Moreover, in vitro cytotoxicity and cell cycle studies were performed in the interaction products prepared with ethanol. The interaction product with sepiolite was biocompatible with the HTC116 line cells, and it did not produce alterations in the cell cycle. However, interaction products with montmorillonite did not produce cell death, but they showed affectation and damage of cells in the cell cycle study at the highest concentration tested (20–100 µM). Therefore, the different organic solvents used are adequate for the improvement of the biopharmaceutical profile of praziquantel. Drug–clay interaction products, specifically with sepiolite, showed very promising results in which new accelerated oral release systems of the praziquantel were obtained. ; Ministerio de Ciencia e Innovacion government PCIN-2017-098 FIS2016-77692-C2-2-P CGL2016-80833-R ; Junta de Andalucia RNM1897 P18-RT-3786

The presence of impurities in medicinal products have to be controlled within safety limits from a pharmaceutical quality perspective. This matter is of special significance for those countries and regions where the directives, guidelines, or legislations, which prescribe the rules for the application of some products is quite selective or incomplete. Clay-based hydrogels are quite an example of this matter since they are topically administered, but, in some regions, they are not subjected to well-defined legal regulations. Since hydrogels establish an intimate contact with the skin, hazardous elements present in the ingredients could potentially be bioavailable and compromise their safety. The elemental composition and mobility of elements present in two hydrogels have been assessed. Sepiolite, palygorskite, and natural spring water were used as ingredients. The release of a particular element mainly depends on its position in the structure of the hydrogels, not only on its concentration in each ingredient. As a general trend, elements' mobility reduced with time. Among the most dangerous elements, whose presence in cosmetics is strictly forbidden by European legal regulations, As and Cd were mobile, although in very low amounts (0.1 and 0.2 g/100 g of hydrogel, respectively). That is, assuming 100% bioavailability, the studied hydrogels would be completely safe at normal doses. Although there is no su cient evidence to confirm that their presence is detrimental to hydrogels safety, legally speaking, their mobility could hinder the authorization of these hydrogels as medicines or cosmetics. In conclusion, the present study demonstrates that hydrogels prepared with sepiolite, palygorskite, and Alicún spring water could be topically applied without major intoxication risks. ; Instituto de Salud Carlos III Spanish Government CGL2016-80833-R ; Junta de Andalucía P18-RT-3786 ; Ministerio de Educación, Cultura y Deporte FPU15/01577

Calcium carbonate is an abundant mineral with several advantages to be a successful carrier to improve oral bioavailability of poorly water-soluble drugs, such as praziquantel. Praziquantel is an antiparasitic drug classified in group II of the Biopharmaceutical Classification System hence characterized by high-permeability and low-solubility. Therefore, the dissolution rate is the limiting factor for the gastrointestinal absorption that contributes to the low bioavailability. Consequently, the therapeutic dose of the praziquantel must be high and big tablets and capsules are required, which are difficult to swallow, especially for pediatric and elderly patients. Mixtures of praziquantel and calcium carbonate using solid-solid physical mixtures and solid dispersions were prepared and characterized using several techniques (X-ray diffraction differential scanning calorimetry, thermogravimetric analysis, scanning electron microscopy, laser diffraction, Fourier transform infrared and Raman spectroscopies). Solubility of these formulations evidenced that the solubility of praziquantel-calcium carbonate interaction product increased in physiological media. In vitro dissolution tests showed that the interaction product increased the dissolution rate of the drug in acidic medium. Theoretical models were studied to understand this experimental behavior. Cytotoxicity and cell cycle studies were performed, showing that praziquantel-calcium carbonate physical mixture and interaction product were biocompatible with the HTC116 cells, because it did not produce a decrease in cell viability or alterations in the cell cycle. ; We also acknowledge for financial support the MINECO, for projects FIS2016-77692-C2-2-P and CGL2016-80833-R, and the Andalusian government, for project RNM1897.