Multidrug delivery system based on polysaccharide nanocomplexes for controlled delivery of a combination of chemotherapeutics

Abstract

Development of delivery systems able to hold and release a combination of bioactive compounds at the target site represents a strategy for improving the therapeutic outcomes and overcome the central issues in the multitherapeutic approach. A delivery system based on polysaccharides suitable for loading a combination of chemotherapeutic drugs, doxorubicin and 5-fluorouracil, at defined weight ratio and deliver them following a pH-dependent kinetics was developed. Nanocomplexes were prepared by polyelectrolytes complexation and characterised in terms of average dimension, morphology, drug content by dynamic light scattering, transmission and scanning microscope and UV–Vis spectroscopy, respectively. The complexes showed a spherical shape with the hydrodynamic diameter between 100 and 130 nm, positive ς-potential, high stability in physiological environment and up to 800 μg of drugs per mg loaded. Release studies demonstrate a pH-dependent trend with high control of the release rate for each compound. In vitro hemocompatibility and not cytotoxicity were observed. In vitro studies showed a significate reduction of the cell viability after contact with the dual-drug loaded complexes than the single-loaded and free-drug formulations demonstrating the synergic effect of the drugs and the advantages of using the complexes. The results show the potential application of the nanosystems for multiple-drug delivery in therapy. © 2019 Elsevier B.V.