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

The impact of chitosan (CS) characteristics (deacetilation 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 investigated in the paper. Information about the incorporation of LAP within the CS-LAP nanocomposites were 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 the values of the swelling ratio of about 6-18, for the CS-LAP composites prepared with one freeze drying (1FD) step, and of about 22-40, for the composites prepared with 2FD steps. The average pore size and pore size distribution were evaluated using software assisted analysis of SEM micrographs. The elastic modulus ranged between 6 - 21 kPa for CS-LAP composites prepared with 1FD, and between 2 - 10 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-fluorouracil (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 oC. The CS-LAP composites with the lowest swelling ratio, prepared by 1FD strategy, 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 in 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.