Abstract
Clay minerals have been widely applied through human history. For instance research in archaeological sites shows their use to build tools or applied as medicine from prehistoric times. This wide range of applications results from the unique clay minerals properties, such as porosity, water adsorption ability, charged nano-layered structure. It is in this context that this thesis was developed. Here further understanding on the physico-chemical properties that influence capture and release of Ciprofloxacin (CIPRO, C17H18FN3O3), an antibiotic agent, water molecules, and cations by Li-fluorohectorite (LiFh, Li1.2(Mg4.8Li1.2)Si8O20F4), a synthetic clay mineral from the smectite family, have been experimentally analyzed. By means of X-rays powder diffraction (XRD), using both an in-house instrument and synchrotron radiation, UV-Vis spectroscopy, Thermogravimetric Analysis coupled to an Infrared spectrometer (TGA/IR), Differential Scanning Calorimetry (DSC), Energy Dispersive X-ray Spectroscopy (EDS) and Inelastic Neutron Scattering using the Elastic Fixed Window approach (EFW), the dynamics of cation exchange process, hydration behavior as a function of interlayer cation and, most importantly, CIPRO intercalation in (and release from) fluorohectorite (Fh) have been studied.
Firstly, concerning the cation exchange process, using XRD and EDS we verified that the exchange either from Li+ to Na+ or from Li+ to Ni2+ in Fh occurs within 5 minutes, while the inverse path exceeds the time scale of the experimental conditions, i.e. 60 minutes of data collection. A similar behavior was observed during the XRD studies of capture and release of CIPRO. These results were interpreted based on the selectivity rule among cations.
Secondly regarding the dependence of the water absorption behavior on the interlayer cation, from XRD, TGA/IR and DSC studies of NiFh we observed that the transition between hydrated states does not occur in abrupt steps, such as in the case of LiFh and NaFh. In addition we were able to demonstrate that the average NiFh clay particle size decreases when the material is in a transition state between two pure hydration states, while the clay crystal lattice strain increases with relative humidity.
Finally, by means of XRD, TGA/IR, UV-Vis and EFW approach, we investigate the capture of CIPRO by LiFh forming a drug delivery complex hereafter called CPFh. This study was carried out as a function of time, temperature and pH. From these data we were able to show that CIPRO’s capture is pH-dependent, being more efficient at acidic pHs. Moreover, we demonstrated that Fh can capture at least 25 % more CIPRO than other systems reported on literature. In addition, based on the thermo-analysis and inelastic neutron scattering data we established that the drug presence into the interlayer space of Fh is weakening the water-clay interactions. Furthermore, CIPRO’s release from Fh in synthetic gastric acid juice (SGA) as a function of time and temperature was also carefully followed. Our studies showed that controlled CIPRO’s release from the clay layers is mostly thermally activated during the first 20 hours and that the value of Arrhenius activation energy indicates that the CIPRO’s release, like the CIPRO’s capture can be discussed as a diffusion-controlled cation exchange process. Finally, via bacterial and toxicological tests, we demonstrated that the effectiveness and toxicity of pure CIPRO is unaffected in the clay-drug complex. To conclude, the high drug adsorption capacity as well as the slow and gradual release from CIPRO when intercalated in Fh adds this synthetic smectite to the list of promising drug carriers.
Firstly, concerning the cation exchange process, using XRD and EDS we verified that the exchange either from Li+ to Na+ or from Li+ to Ni2+ in Fh occurs within 5 minutes, while the inverse path exceeds the time scale of the experimental conditions, i.e. 60 minutes of data collection. A similar behavior was observed during the XRD studies of capture and release of CIPRO. These results were interpreted based on the selectivity rule among cations.
Secondly regarding the dependence of the water absorption behavior on the interlayer cation, from XRD, TGA/IR and DSC studies of NiFh we observed that the transition between hydrated states does not occur in abrupt steps, such as in the case of LiFh and NaFh. In addition we were able to demonstrate that the average NiFh clay particle size decreases when the material is in a transition state between two pure hydration states, while the clay crystal lattice strain increases with relative humidity.
Finally, by means of XRD, TGA/IR, UV-Vis and EFW approach, we investigate the capture of CIPRO by LiFh forming a drug delivery complex hereafter called CPFh. This study was carried out as a function of time, temperature and pH. From these data we were able to show that CIPRO’s capture is pH-dependent, being more efficient at acidic pHs. Moreover, we demonstrated that Fh can capture at least 25 % more CIPRO than other systems reported on literature. In addition, based on the thermo-analysis and inelastic neutron scattering data we established that the drug presence into the interlayer space of Fh is weakening the water-clay interactions. Furthermore, CIPRO’s release from Fh in synthetic gastric acid juice (SGA) as a function of time and temperature was also carefully followed. Our studies showed that controlled CIPRO’s release from the clay layers is mostly thermally activated during the first 20 hours and that the value of Arrhenius activation energy indicates that the CIPRO’s release, like the CIPRO’s capture can be discussed as a diffusion-controlled cation exchange process. Finally, via bacterial and toxicological tests, we demonstrated that the effectiveness and toxicity of pure CIPRO is unaffected in the clay-drug complex. To conclude, the high drug adsorption capacity as well as the slow and gradual release from CIPRO when intercalated in Fh adds this synthetic smectite to the list of promising drug carriers.
| Original language | English |
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| Publisher | The Niels Bohr Institute, Faculty of Science, University of Copenhagen |
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| Publication status | Published - 2017 |