Nanocomposites de quitosano y montmorillonita como promotores de la permeabilidad celular de oxitetraciclina

Abstract

This thesis has been carried out in the Andalusian research group CTS-946 "Pharmaceutical development of natural resources". Pharmaceutical development of new materials based on nanoscale interactions between natural occurring excipients is one of the research lines of the group. This is the research area in which this thesis work was focused, and in particular, in the preparation, and characterization of chitosan/montmorillonite nanocomposites to be used as nanocarriers of oxytetracycline. With this aim, it was firstly reviewed the possibility of obtaining hybrid nanostructures materials with the selected polysaccharide and phyllosilicate and their expected biopharmaceutical and technological features. Then, we proceed to prepare nanocomposites by solid-liquid contact of the components and to evaluate the resulting structure and possible interaction mechanism. The obtained results showed that chitosan was effectively retained by montmorillonite particles through cation exchange. The new material showed good biocompatibility in the range 5¿500 ¿g/ml, being also able to effectively stimulate cell proliferation over Caco-2 cell cultures. The nanocomposite also possessed mucoadhesive properties and low solubility in acidic environment compared to chitosan alone. These properties led to consider the nanocomposite as a functional excipient able to be coupled with drugs with limited bioavailability due to poor adhesion and deficient transport across the gastrointestinal tract. Oxytetracycline was selected as model drug to evaluate this possibility. The drug was loaded into the nanocomposite and the resulting structure characterized by means of X-Ray diffraction, thermal analysis and FTIR. The results demonstrated that the antibiotic was effectively retained into the nanocomposite structure. The loaded nanocomposite maintained its biocompatibility and overcame the bioavailability uncertainties of the drug. The amount of drug permeated across the cellular substrates also increased as a result of the interaction with the nanocomposite. It can be concluded that by interaction between chitosan and montmorillonite it was possible to obtain a new material that could be use to improve the transport of oxytetracycline across gastrointestinal epithelial cells.