International Journal of Molecular Sciences, Dec 17, 2022
Gemfibrozil (GEM) is a hypolipidemic agent, which is effective in reducing serum cholesterol and ... more Gemfibrozil (GEM) is a hypolipidemic agent, which is effective in reducing serum cholesterol and triglyceride levels. Complexation of GEM with native β-cyclodextrin (β-CD) and with the derivatives hydroxypropyl-β-and randomly methylated β-CD (HPβ-CD and Meβ-CD) was studied in aqueous solution of pH 2.8 and 7.0. The stability constants were determined by spectrofluorimetry, 1 H-NMR spectroscopy and solubility assays. Considering the well-known difficulties to obtain similar stability constants by different techniques, the agreement of the values obtained supports the reliability of the results presented. The advantages and drawbacks of each analytical technique for the study of inclusion complexation were discussed as well. In addition, the thermodynamic parameters of complexation, enthalpy (∆H) and entropy (∆S), were determined and related to the type of molecular interactions that take place between GEM and the different cyclodextrins. Finally, solid dispersions were prepared by co-evaporation, kneading, vacuum desiccation, and coprecipitation, and complexation was evaluated by X-ray diffraction.
Currently, there is a global concern about the environmental problems related to plastic wastes. ... more Currently, there is a global concern about the environmental problems related to plastic wastes. Cellulose acetate (CA) and polylactic acid (PLA) are the most frequently used biopolymers in the food packaging industry. In this work, TiO2 nanoparticles and β-cyclodextrin (βCD) have been incorporated into nanocomposite films made of PLA and CA and then evaluated under biodegradation assays in wastewater to assess the effects of both additives on the biodegradability of films. TiO2 nanoparticles clearly enhanced the biodegradability of CA and PLA; PLA-TiO2 nanocomposites disappeared after 60 days, whereas plain PLA remained present after 100 days. The presence of the additives provided an exponential growth to BOD profiles. FTIR spectra showed a much faster deacetylation of CA for the nanocomposites than for the bare CA, and XRD diffractograms showed that PLA nanocomposites became more amorphous than bare PLA. The thermal resistance of CA and PLA nanocomposites substantially decreased,...
All mammals lose their ability to produce lactase (β-galactosidase), the enzyme that cleaves lact... more All mammals lose their ability to produce lactase (β-galactosidase), the enzyme that cleaves lactose into galactose and glucose, after weaning. The prevalence of lactase deficiency (LD) spans from 2 to 15% among northern Europeans, to nearly 100% among Asians. Following lactose consumption, people with LD often experience gastrointestinal symptoms such as abdominal pain, bowel distension, cramps and flatulence, or even systemic problems such as headache, loss of concentration and muscle pain. These symptoms vary depending on the amount of lactose ingested, type of food and degree of intolerance. Although those affected can avoid the uptake of dairy products, in doing so, they lose a readily available source of calcium and protein. In this work, gels obtained by complexation of Tetronic 90R4 with α-cyclodextrin loaded with β-galactosidase are proposed as a way to administer the enzyme immediately before or with the lactose-containing meal. Both molecules are biocompatible, can form gels in situ, and show sustained erosion kinetics in aqueous media. The complex was characterized by FTIR that evidenced an inclusion complex between the polyethylene oxide block and α-cyclodextrin. The release profiles of β-galactosidase from two different matrices (gels and tablets) of the in situ hydrogels have been obtained. The influence of the percentage of Tetronic in media of different pH was evaluated. No differences were observed regarding the release rate from the gel matrices at pH 6 (t50 = 105 min). However, in the case of the tablets, the kinetics were faster and they released a greater amount of 90R4 (25%, t50 = 40–50 min). Also, the amount of enzyme released was higher for mixtures with 25% Tetronic. Using suitable mathematical models, the corresponding kinetic parameters have been calculated. In all cases, the release data fit quite well to the Peppas–Sahlin model equation, indicating that the release of β-galactosidase is governed by a combination of diffusion and erosion processes. It has been observed that the diffusion mechanism prevails over erosion during the first 50 minutes, followed by continued release of the enzyme due to the disintegration of the matrix
Lower freezing temperatures change the porus structure of CS-PVA hydrogels. The CS-PVA hydrog... more Lower freezing temperatures change the porus structure of CS-PVA hydrogels. The CS-PVA hydrogels released diflunisal drug in controlled manner during 30 h. A new mathematical model predicting physical and structural behavior is proposed.
The pharmaceutical applications of cyclodextrins (CDs), cyclic oligosaccharides capable of includ... more The pharmaceutical applications of cyclodextrins (CDs), cyclic oligosaccharides capable of including hydrophobic molecules inside their cavities, have been known for decades. Besides the solubilising and encapsulating abilities of natural and modified CDs due to the formation of inclusion complexes, there is an increasing interest in organized macrostructures based on CDs as potential drug delivery devices and gene carrier systems. The present review discusses first the case of drug carriers based on monomeric modified CDs (amphiphilic and CD core-star polymers), in which self-assembly plays a major role. Polyrotaxanes, i.e., CDs threaded onto a polymer chain, are then reviewed in relation to their pharmaceutical applications. Finally, covalently linked CDs, either by grafting or crosslinking, are analyzed, including more complex structures formed by assembling CDcontaining networks or chains. We have tried along this review to cover the most recent developments on these structures ...
Abstract Complexation of glisentide with α -, β - and γ -cyclodextrin (CD) has been investigated ... more Abstract Complexation of glisentide with α -, β - and γ -cyclodextrin (CD) has been investigated in aqueous solution and in the solid state. Complex formation in solution has been analysed using solubility diagrams and NMR spectroscopy and the interaction in solid state has been studied by X-ray diffractometry, DSC and IR spectroscopy. The thermodynamic parameters, Δ H °, Δ S ° and Δ G °, of complexation with β - and γ -CD have been calculated from the temperature dependence of the stability constant. The process has been found to be exothermic and Δ S ° is slightly unfavourable. In addition, it has been found that the ionization state of glisentide plays an important role in complexation and the fact that the extent of complexation is greater with β - than with γ -CD has revealed the importance of the cavity size to get an adequate fitting between host and guest molecules. The inclusion of the ortho -substituted aromatic ring of glisentide has been evidenced by NMR spectroscopy. Finally, complexes have been prepared by coprecipitation and kneading methods and it has been found that the former is more suitable to achieve solid-state complexation.
Abstract A spectrofluorimetric method to study the interactions of naproxen with 1-vinyl-2-pyrrol... more Abstract A spectrofluorimetric method to study the interactions of naproxen with 1-vinyl-2-pyrrolidone and β -cyclodextrin in aqueous solution has been proposed. As complexation causes appreciable spectral changes, this method enables the determination of the stability constants. Complexation with β -cyclodextrin results in an enhancement of the fluorescence of naproxen whereas 1-vinyl-2-pyrrolidone involves a quenching of fluorescence. It has been supposed 1:1 complex formation. Specifically, formation constants, enthalpy and entropy values have been obtained for the aforementioned complexes at different temperatures and pH values; their associated errors are given.
Polymeric materials, such as polyvinyl alcohol (PVA) and ethylene–PVA copolymers (EVOH) are widel... more Polymeric materials, such as polyvinyl alcohol (PVA) and ethylene–PVA copolymers (EVOH) are widely used in the food sector as packaging materials because of their excellent properties. TiO2 nanoparticles (NPs) show photocatalytic activity; when added to the aforementioned polymers, on the one hand, they are expected to provide bactericidal capacity, whereas on the other hand, they could favor nanocomposite degradation. These types of nanoparticles can be derivatized with cyclodextrin macromolecules (CDs), which can act as food preservative carriers, increasing the packaging food protective properties. In this work, films containing β-Cyclodextrin (βCD)-grafted TiO2 nanoparticles and PVA or EVOH were prepared. Regarding the photocatalytic activity of the nanoparticles and the possible environmental protection, accelerated aging tests for PVA, EVOH, and their composites with cyclodextrin-grafted TiO2 nanoparticle (NP) films were performed by two methods, namely, stability chamber expe...
An original family of multivalent vectors encompassing gemini and facial amphiphilicy, namely cat... more An original family of multivalent vectors encompassing gemini and facial amphiphilicy, namely cationic Siamese twin surfactants, has been prepared from the disaccharide trehalose; molecular engineering let modulate the self-assembling properties...
The complexation of naftifine (NF) and terbinafine (TB) with cyclodextrins (CDs) has been investi... more The complexation of naftifine (NF) and terbinafine (TB) with cyclodextrins (CDs) has been investigated by UV/visible and 1 H NMR spectroscopy, ROESY techniques and also ESI-MS. Both drugs form 1:1 inclusion complexes with all the CDs tested except with α-CD, as deduced from the ...
Engineering of multifunctional drug nanocarriers combining stability and good release properties ... more Engineering of multifunctional drug nanocarriers combining stability and good release properties remains a great challenge. In this work, natural polymers κ-carrageenan (κ-CAR) and chitosan (CS) were deposited onto olive oil nanoemulsion droplets (NE) via layer-by-layer (LbL) self-assembly to study the release mechanisms of the anti-inflammatory diflunisal (DF) as a lipophilic drug model. The nano-systems were characterized by dynamic light scattering (DLS), zeta potential (ζ-potential) measurements, transmission electron microscopy (TEM), scanning electron microscopy (SEM), X-ray energy dispersive spectroscopy (XEDS) and Fourier transform infrared spectroscopy (FTIR) to confirm the NE-coating with polymer layers. In addition, kinetic release studies of DF were developed by the dialysis diffusion bag technique. Mathematical models were applied to investigate the release mechanisms. The results showed that stable and suitably sized nanocapsules (~300 nm) were formed. Also, the consecutive adsorption of polyelectrolytes by charge reversal was evidenced. More interestingly, the drug release mechanism varied depending on the number of layers deposited. The nanosized systems containing up to two layers showed anomalous transport and first order kinetics. Formulations with three and four layers exhibited Case II transport releasing diflunisal with zero order kinetics. Hence, our results suggest that these polyelectrolyte nanocapsules have great potential as a multifunctional nanocarrier for drug delivery applications.
International Journal of Molecular Sciences, Dec 17, 2022
Gemfibrozil (GEM) is a hypolipidemic agent, which is effective in reducing serum cholesterol and ... more Gemfibrozil (GEM) is a hypolipidemic agent, which is effective in reducing serum cholesterol and triglyceride levels. Complexation of GEM with native β-cyclodextrin (β-CD) and with the derivatives hydroxypropyl-β-and randomly methylated β-CD (HPβ-CD and Meβ-CD) was studied in aqueous solution of pH 2.8 and 7.0. The stability constants were determined by spectrofluorimetry, 1 H-NMR spectroscopy and solubility assays. Considering the well-known difficulties to obtain similar stability constants by different techniques, the agreement of the values obtained supports the reliability of the results presented. The advantages and drawbacks of each analytical technique for the study of inclusion complexation were discussed as well. In addition, the thermodynamic parameters of complexation, enthalpy (∆H) and entropy (∆S), were determined and related to the type of molecular interactions that take place between GEM and the different cyclodextrins. Finally, solid dispersions were prepared by co-evaporation, kneading, vacuum desiccation, and coprecipitation, and complexation was evaluated by X-ray diffraction.
Currently, there is a global concern about the environmental problems related to plastic wastes. ... more Currently, there is a global concern about the environmental problems related to plastic wastes. Cellulose acetate (CA) and polylactic acid (PLA) are the most frequently used biopolymers in the food packaging industry. In this work, TiO2 nanoparticles and β-cyclodextrin (βCD) have been incorporated into nanocomposite films made of PLA and CA and then evaluated under biodegradation assays in wastewater to assess the effects of both additives on the biodegradability of films. TiO2 nanoparticles clearly enhanced the biodegradability of CA and PLA; PLA-TiO2 nanocomposites disappeared after 60 days, whereas plain PLA remained present after 100 days. The presence of the additives provided an exponential growth to BOD profiles. FTIR spectra showed a much faster deacetylation of CA for the nanocomposites than for the bare CA, and XRD diffractograms showed that PLA nanocomposites became more amorphous than bare PLA. The thermal resistance of CA and PLA nanocomposites substantially decreased,...
All mammals lose their ability to produce lactase (β-galactosidase), the enzyme that cleaves lact... more All mammals lose their ability to produce lactase (β-galactosidase), the enzyme that cleaves lactose into galactose and glucose, after weaning. The prevalence of lactase deficiency (LD) spans from 2 to 15% among northern Europeans, to nearly 100% among Asians. Following lactose consumption, people with LD often experience gastrointestinal symptoms such as abdominal pain, bowel distension, cramps and flatulence, or even systemic problems such as headache, loss of concentration and muscle pain. These symptoms vary depending on the amount of lactose ingested, type of food and degree of intolerance. Although those affected can avoid the uptake of dairy products, in doing so, they lose a readily available source of calcium and protein. In this work, gels obtained by complexation of Tetronic 90R4 with α-cyclodextrin loaded with β-galactosidase are proposed as a way to administer the enzyme immediately before or with the lactose-containing meal. Both molecules are biocompatible, can form gels in situ, and show sustained erosion kinetics in aqueous media. The complex was characterized by FTIR that evidenced an inclusion complex between the polyethylene oxide block and α-cyclodextrin. The release profiles of β-galactosidase from two different matrices (gels and tablets) of the in situ hydrogels have been obtained. The influence of the percentage of Tetronic in media of different pH was evaluated. No differences were observed regarding the release rate from the gel matrices at pH 6 (t50 = 105 min). However, in the case of the tablets, the kinetics were faster and they released a greater amount of 90R4 (25%, t50 = 40–50 min). Also, the amount of enzyme released was higher for mixtures with 25% Tetronic. Using suitable mathematical models, the corresponding kinetic parameters have been calculated. In all cases, the release data fit quite well to the Peppas–Sahlin model equation, indicating that the release of β-galactosidase is governed by a combination of diffusion and erosion processes. It has been observed that the diffusion mechanism prevails over erosion during the first 50 minutes, followed by continued release of the enzyme due to the disintegration of the matrix
Lower freezing temperatures change the porus structure of CS-PVA hydrogels. The CS-PVA hydrog... more Lower freezing temperatures change the porus structure of CS-PVA hydrogels. The CS-PVA hydrogels released diflunisal drug in controlled manner during 30 h. A new mathematical model predicting physical and structural behavior is proposed.
The pharmaceutical applications of cyclodextrins (CDs), cyclic oligosaccharides capable of includ... more The pharmaceutical applications of cyclodextrins (CDs), cyclic oligosaccharides capable of including hydrophobic molecules inside their cavities, have been known for decades. Besides the solubilising and encapsulating abilities of natural and modified CDs due to the formation of inclusion complexes, there is an increasing interest in organized macrostructures based on CDs as potential drug delivery devices and gene carrier systems. The present review discusses first the case of drug carriers based on monomeric modified CDs (amphiphilic and CD core-star polymers), in which self-assembly plays a major role. Polyrotaxanes, i.e., CDs threaded onto a polymer chain, are then reviewed in relation to their pharmaceutical applications. Finally, covalently linked CDs, either by grafting or crosslinking, are analyzed, including more complex structures formed by assembling CDcontaining networks or chains. We have tried along this review to cover the most recent developments on these structures ...
Abstract Complexation of glisentide with α -, β - and γ -cyclodextrin (CD) has been investigated ... more Abstract Complexation of glisentide with α -, β - and γ -cyclodextrin (CD) has been investigated in aqueous solution and in the solid state. Complex formation in solution has been analysed using solubility diagrams and NMR spectroscopy and the interaction in solid state has been studied by X-ray diffractometry, DSC and IR spectroscopy. The thermodynamic parameters, Δ H °, Δ S ° and Δ G °, of complexation with β - and γ -CD have been calculated from the temperature dependence of the stability constant. The process has been found to be exothermic and Δ S ° is slightly unfavourable. In addition, it has been found that the ionization state of glisentide plays an important role in complexation and the fact that the extent of complexation is greater with β - than with γ -CD has revealed the importance of the cavity size to get an adequate fitting between host and guest molecules. The inclusion of the ortho -substituted aromatic ring of glisentide has been evidenced by NMR spectroscopy. Finally, complexes have been prepared by coprecipitation and kneading methods and it has been found that the former is more suitable to achieve solid-state complexation.
Abstract A spectrofluorimetric method to study the interactions of naproxen with 1-vinyl-2-pyrrol... more Abstract A spectrofluorimetric method to study the interactions of naproxen with 1-vinyl-2-pyrrolidone and β -cyclodextrin in aqueous solution has been proposed. As complexation causes appreciable spectral changes, this method enables the determination of the stability constants. Complexation with β -cyclodextrin results in an enhancement of the fluorescence of naproxen whereas 1-vinyl-2-pyrrolidone involves a quenching of fluorescence. It has been supposed 1:1 complex formation. Specifically, formation constants, enthalpy and entropy values have been obtained for the aforementioned complexes at different temperatures and pH values; their associated errors are given.
Polymeric materials, such as polyvinyl alcohol (PVA) and ethylene–PVA copolymers (EVOH) are widel... more Polymeric materials, such as polyvinyl alcohol (PVA) and ethylene–PVA copolymers (EVOH) are widely used in the food sector as packaging materials because of their excellent properties. TiO2 nanoparticles (NPs) show photocatalytic activity; when added to the aforementioned polymers, on the one hand, they are expected to provide bactericidal capacity, whereas on the other hand, they could favor nanocomposite degradation. These types of nanoparticles can be derivatized with cyclodextrin macromolecules (CDs), which can act as food preservative carriers, increasing the packaging food protective properties. In this work, films containing β-Cyclodextrin (βCD)-grafted TiO2 nanoparticles and PVA or EVOH were prepared. Regarding the photocatalytic activity of the nanoparticles and the possible environmental protection, accelerated aging tests for PVA, EVOH, and their composites with cyclodextrin-grafted TiO2 nanoparticle (NP) films were performed by two methods, namely, stability chamber expe...
An original family of multivalent vectors encompassing gemini and facial amphiphilicy, namely cat... more An original family of multivalent vectors encompassing gemini and facial amphiphilicy, namely cationic Siamese twin surfactants, has been prepared from the disaccharide trehalose; molecular engineering let modulate the self-assembling properties...
The complexation of naftifine (NF) and terbinafine (TB) with cyclodextrins (CDs) has been investi... more The complexation of naftifine (NF) and terbinafine (TB) with cyclodextrins (CDs) has been investigated by UV/visible and 1 H NMR spectroscopy, ROESY techniques and also ESI-MS. Both drugs form 1:1 inclusion complexes with all the CDs tested except with α-CD, as deduced from the ...
Engineering of multifunctional drug nanocarriers combining stability and good release properties ... more Engineering of multifunctional drug nanocarriers combining stability and good release properties remains a great challenge. In this work, natural polymers κ-carrageenan (κ-CAR) and chitosan (CS) were deposited onto olive oil nanoemulsion droplets (NE) via layer-by-layer (LbL) self-assembly to study the release mechanisms of the anti-inflammatory diflunisal (DF) as a lipophilic drug model. The nano-systems were characterized by dynamic light scattering (DLS), zeta potential (ζ-potential) measurements, transmission electron microscopy (TEM), scanning electron microscopy (SEM), X-ray energy dispersive spectroscopy (XEDS) and Fourier transform infrared spectroscopy (FTIR) to confirm the NE-coating with polymer layers. In addition, kinetic release studies of DF were developed by the dialysis diffusion bag technique. Mathematical models were applied to investigate the release mechanisms. The results showed that stable and suitably sized nanocapsules (~300 nm) were formed. Also, the consecutive adsorption of polyelectrolytes by charge reversal was evidenced. More interestingly, the drug release mechanism varied depending on the number of layers deposited. The nanosized systems containing up to two layers showed anomalous transport and first order kinetics. Formulations with three and four layers exhibited Case II transport releasing diflunisal with zero order kinetics. Hence, our results suggest that these polyelectrolyte nanocapsules have great potential as a multifunctional nanocarrier for drug delivery applications.
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