Physicochemical and Mechanical Evaluation of Nanocomposite Cryogels Based on Chitosan and Laponite and Their Potential for Drug Delivery.

It is known that the controlled release of anticancer drugs with low molecular weight from drug delivery systems (DDSs) based on polysaccharides such as chitosan (CS) still encounter certain difficulties because of the high hydrophilicity of the carrier. The release rate is very fast, with a burst release that is usually obvious. Therefore, finding novel systems to carry and release low molecular weight drugs such as 5-fluorouracil (5-FU) is still of interest. The impact of chitosan (CS) characteristics (deacetylation degree and molar mass), and concentration as well as of the strategy employed to fabricate porous nanocomposites CS-laponite (LAP), on the physicochemical properties of CS-LAP sponges was first investigated in the paper. Information about the incorporation of LAP within the CS-LAP nanocomposites was obtained by EDX and FTIR spectroscopy. The influence of the fabrication conditions on the physical cross-linking was evidenced first by the swelling of the composite sponges at equilibrium in distilled water, with lower values of the swelling ratio found for the composites prepared with one freeze-drying (1FD) step, than of those prepared with 2FD steps. The elastic modulus ranged between 6 and 21 kPa for CS-LAP composites prepared with 1FD, and between 2 and 10 kPa for the nanocomposites prepared with 2FD steps. The physicochemical properties of CS-LAP nanocomposite sponges were correlated with their behavior in the loading and in vitro release of 5-FU as a function of pH. It was found that the CS-LAP composites with the highest swelling ratio exhibited the fastest release of 5-FU in simulated gastric fluid (pH 2.0), with the cumulative release in the range of 85-100%, in about 60 min, at 37 °C. The CS-LAP composites with the lowest swelling ratio, displayed the slowest release rate of drug. The drug release from the double component composites was accompanied by the carrier dissolution/disintegration. To retard the release of 5-FU in the gastric environment, the drug was sealed in the porous CS-LAP nanocomposites by simple complexation of the free positive charges of CS with carboxymethylcellulose as polyanion. These systems kept their integrity at pH 2.0, pH 6.8 and phosphate buffer with pH 7.4, and released 5-FU in a controlled manner, making them suitable systems for delivery of 5-FU in both the stomach and small intestine.