Chitosan - dextran phosphate carbamate hydrogels for locally controlled co-delivery of doxorubicin and indomethacin: From computation study to in vivo pharmacokinetics.

The development of synergistic drug combinations is a promising strategy for effective cancer suppression. Here, we report all-polysaccharide biodegradable polyelectrolyte complex hydrogels (DPCS) based on dextran phosphate carbamate (DP) and chitosan (CS) for controlled co-delivery of the anticancer drug doxorubicin (DOX) and the non-steroidal anti-inflammatory drug indomethacin (IND). IND can induce more apoptosis in tumor cells by reducing the level of multidrug resistance-associated protein 1. Based on calculations using density functional theory and zeta potential analysis data, carriers with high drug loading were obtained. The release profile of both drugs from the hydrogels was tuned by changing the molecular weight and functional groups content of the polysaccharides. The optimized DPCS showed a steady release of DOX both in vitro and in vivo, and a gradual release of IND, which constantly induced the action of DOX. Considering all of these benefits, DOX- and IND-loaded DPCS offer a promising long-acting polysaccharide-based antitumor platform.

Biodegradable polyelectrolyte complexes of chitosan and partially crosslinked dextran phosphate with potential for biomedical applications.

Polyelectrolyte complexes (PECs) are spontaneously formed by mixing oppositely charged polyelectrolyte solutions without the use of organic solvents and chemical crosslinkers are great candidate carriers for drug delivery. Herein, biodegradable antimicrobial polyelectrolyte complexes of chitosan - dextran phosphate (DPCS) containing cefazolin were developed and characterized in order to assess their suitability for biomedical applications. For this purpose, the simultaneous partial crosslinking and functionalization of dextran with phosphoric acid in a urea melt under reduced pressure were studied. The functional group content and molecular weight of dextran phosphate were varied in order to establish their influence on gel fraction yield, thermal properties and morphologies of the hydrogels. The stoichiometric PECs of DPCS showed good in vitro biocompatibility, pH sensitivity and biodegradability depending on the hydrogel composition. The release of drug from cefazolin-loaded DPCS hydrogels was through non-Fickian diffusion and displayed long sustained-release time. The drug-loaded hydrogels showed antimicrobial activity against Gram-negative Escherichia coli and Gram-positive Staphylococcus aureus. The tunable degradation behavior under physiological conditions in combination with biocompatibility of the pristine DPCS and high antibacterial efficacy drug-loaded hydrogels may render the presented materials interesting for biomedical applications.