The development of 3D printable hydrogels based on the crosslinking between chitosan and gelatin is proposed. Chitosan and gelatin were both functionalized with methyl furan groups. Chemical modification was performed by reductive amination with methyl furfural involving the lysine residues of gelatin and the amino groups of chitosan to generate hydrogels with tailored properties. The methyl furan residues present in both polymers were exploited for efficient crosslinking via Diels-Alder ligation with PEG-Star-maleimide under cell-compatible conditions. The obtained chitosan-gelatin hybrid was employed to formulate hydrogels and 3D printable biopolymers and its processability and biocompatibility were preliminarily investigated.
In a collaborative study involving six laboratories in the USA, Europe, and India the molecular weight distributions of a panel of heparin sodium samples were determined, in order to compare heparin sodium of bovine intestinal origin with that of bovine lung and porcine intestinal origin. Porcine samples met the current criteria as laid out in the USP Heparin Sodium monograph. Bovine lung heparin samples had consistently lower average molecular weights. Bovine intestinal heparin was variable in molecular weight; some samples fell below the USP limits, some fell within these limits and others fell above the upper limits. These data will inform the establishment of pharmacopeial acceptance criteria for heparin sodium derived from bovine intestinal mucosa. The method for MW determination as described in the USP monograph uses a single, broad standard calibrant to characterize the chromatographic profile of heparin sodium on high-resolution silica-based GPC columns. These columns may be short-lived in some laboratories. Using the panel of samples described above, methods based on the use of robust polymer-based columns have been developed. In addition to the use of the USP’s broad standard calibrant for heparin sodium with these columns, a set of conditions have been devised that allow light-scattering detected molecular weight characterization of heparin sodium, giving results that agree well with the monograph method. These findings may facilitate the validation of variant chromatographic methods with some practical advantages over the USP monograph method.
Mitoxantrone (MTX) is an antineoplastic agent whose use is limited by serious side effects on non-neoplastic cells. The aim of this study was the development of a new drug release system using an ionotropic gelation technique for microencapsulation of MTX in chitosan-carboxymethylinulin nanoparticles (CCInp), followed by evaluation of their cytotoxic effects on neoplastic MDA-MB-231 and non-neoplastic NIH3T3 cell lines. The CCInp were prepared through a new reliable method for easy functionalization of both inulin and chitosan. Both unloaded and drug-loaded nanoparticles were characterized by transmission electron microscopy (TEM) and dynamic light scattering (DLS) and showed a spherical morphology with an average hydrodynamic diameter between 40 and 80 nm. Both nanoparticles were stable and easily degraded by lysozyme. MTX-loaded nanoparticles led to a greater mortality of MDA-MB-231 relative to free drug due to the ability of the nanoparticles to accumulate preferentially in neoplastic cells. The developed drug release system retains the ability to kill MDA-MB-231 cells in vitro, improving the survival of NIH3T3 cells.
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