Formulation and Evaluation of Chitosan Nanospheres Containing Methotrexate Targeted Drug Delivery System

Objective: The aim of the present study is to prepare and evaluate nanoparticles containing methotrexate using chitosan as the polymer. The MTX-loaded CS-NPs were prepared by the emulsion polymerization method using glutaraldehyde as the cross-linking agent. Methods: CS nanospheres prepared using 1.0% w/v chitosan gel (in 4.0% v/v glacial acetic acid), 2.5 mg, 5.0 mg and 10 mg of MTX, 6.0 mL GST and 0.6 mL Span 80 yielded the most satisfactory product. Formulation was optimized and in vitro drug release was performed. In-vitro release study was done in HPLC water. Results: The MTX-loaded CS-NPs were formed by the emulsion polymerization method. The particle size, loading efficiency and in-vitro release varied from 779.9 to 3079.0 nm, 70.93 to 82.68% and 10.29 to 84.67%, respectively for the formulated sample. Release kinetics showed diffusion-controlled and Non-Fickian release pattern. The zeta potential of three formulations achieved optimum values between -16.8 to 23.3 mV. Optimum zeta potential is essential for the uniformity of the nanoparticles size distribution. CS-MTX has shown a sustained release pattern in vitro. Conclusion: The sample C (10.0 mg) showed the least particle size, optimum zeta potential range, moderate drug loading efficiency followed by sustained drug release over 48 hours. Hence, this formulation satisfactorily maintain the bioavailability and targeting efficiency towards cancer cell. Thus, the nano-formulation has a potential to be a sustained release, passive targeted delivery system for MTX, with reduced side effects associated with the drug.