No abstract

Chitosan nanoparticles (CSNPs) ionically crosslinked with tripolyphosphate salts (TPP) were employed as nanocarriers in combined drug delivery and magnetic hyperthermia (MH) therapy. To that aim, three different ferrofluid concentrations and a constant 5-fluorouracil (5-FU) concentration were efficiently encapsulated to yield magnetic CSNPs with core-shell morphology. In vitro experiments using normal cells, fibroblasts (FHB) and cancer cells, human glioblastoma A-172, showed that CSNPs presented a dose-dependent cytotoxicity and that they were successfully uptaken into both cell lines. The application of a MH treatment in A-172 cells resulted in a cell viability of 67-75% whereas no significant reduction of cell viability was observed for FHB. However, the A-172 cells showed re-growth populations 4h after the application of the MH treatment when CSNPs were loaded only with ferrofluid. Finally, a combined effect of MH and 5-FU release was observed with the application of a second MH treatment for CSNPs exhibiting a lower amount of released 5-FU. This result demonstrates the potential of CSNPs for the improvement of MH therapies.

Magnetite nanoparticles have been successfully synthesized in the presence of chitosan using an in situ coprecipitation method in alkali media. This method allows obtaining chitosan ferrogels due to the simultaneous gelation of chitosan. The chitosan concentration has been varied and its effects on the particle synthesis investigated. It has been demonstrated that high chitosan concentrations prevents the formation of magnetite due to the slow diffusion of the alkali species through the viscous medium provided by chitosan, instead iron hydroxides are formed. The presence of magnetite nanoparticles increases the elastic modulus which results in a reinforcement of the chitosan ferrogels. This effect is counterbalanced by the disruption of hydrogen bonding responsible for the formation of chitosan hydrogels in alkali media.

No abstract

Composite ferrogels were obtained by encapsulation of magnetic nanoparticles at two different concentrations (2.0 and 5.0 % w/v) within mixed agarose/chitosan hydrogels having different concentrations of agarose (1.0, 1.5 and 2.0% (w/v)) and a fixed concentration of chitosan (0.5% (w/v)). The morphological characterization carried out by scanning electron microscopy showed that dried composite ferrogels present pore sizes in the micrometer range. Thermogravimetric measurements showed that ferrogels present higher degradation temperatures than blank chitosan/agarose hydrogels without magnetic nanoparticles. In addition, measurements of the elastic moduli of the composite ferrogels evidenced that the presence of magnetic nanoparticles in the starting aqueous solutions prevents to some extent the agarose gelation achieved by simply cooling chitosan/agarose aqueous solutions. Finally, it is shown that composite chitosan/agarose ferrogels are able to heat in response to the application of an alternating magnetic field so that they can be considered as potential biomaterials to be employed in magnetic hyperthermia treatments.

No abstract

In the present work, we report on the preparation of microgels of chitosan crosslinked with sodium tripolyphosphate (TPP) employing the microfluidics technique (MF). To achieve this, several flow focusing geometries were designed and tested. As a first step, a two-inlet flow focusing geometry was employed to emulsify chitosan and the crosslinking reaction was carried out offchip. This procedure did not allow separating the resulting chitosan microgels due to an incomplete crosslinking reaction. A crosslinking reaction on-chip was studied as an alternative. A four-inlet flow focusing geometrywas designed in which three dispersed phases, chitosan 0.25% (w/v), TPP 0.05% (w/v) and acetic acid 1% (v/v) and an continuous phase mineral oil + Span 80 (3% w/v) were employed. The flow rates for the continuous phase were varied from 6.7 to 11.7 μL/min and chitosan microgels were successfully obtained with average diameters from 68 to 42 μm. The average size of the microgels outside the MF device decreased up to ~21% with respect to their size inside the MF device due to partial expulsion of water from the microgels when complete gelation occurred.