Nanoparticles consisting of N-trimethyl chitosan (TMC) and alginate complexed with cisplatin were prepared. TMC a freely soluble quaternized derivative of chitosan with cell permeability properties, was synthesized by reductive methylation. The product was characterized by NMR spectroscopy to ascertain the degree of quaternization. Nanoparticles were obtained by interaction of TMC and the cisplatin-alginate complex at different ratios (w/w). A Doehlert experimental design was used to opimized the formulation. Particle sizesand size distribution were determined by PCS whereas the zeta potential was obtained by electrophoretic mobility measurements. Particle yield was calculated by an indirect method and the drug release profile was studied by a dialysis experiment. Results from PCS indicate that nanoparticles showed sizes of 300-400 nm, with a nearly monomodal size distribution. The zeta potential was found to be positive 25-30 mV. Particle yield was in the range of 30-50% and cisplatin was released in a sustained manner, in comparison with the starting alginate/cisplatin complex. Preliminary results from an in vitro nanoparticles have an inhibiting activity similar or even better than cisplatin on human A549 and A2780 and murine P388 cell lines.
Preparation and evaluation of N-trimethyl chitosan/alginate nanoparticles containing cisplatin complexed with alginate
CAFAGGI, SERGIO;RUSSO, ELEONORA;CAVIGLIOLI, GABRIELE;PARODI, BRUNELLA;BIGNARDI, GAETANO
2006-01-01
Abstract
Nanoparticles consisting of N-trimethyl chitosan (TMC) and alginate complexed with cisplatin were prepared. TMC a freely soluble quaternized derivative of chitosan with cell permeability properties, was synthesized by reductive methylation. The product was characterized by NMR spectroscopy to ascertain the degree of quaternization. Nanoparticles were obtained by interaction of TMC and the cisplatin-alginate complex at different ratios (w/w). A Doehlert experimental design was used to opimized the formulation. Particle sizesand size distribution were determined by PCS whereas the zeta potential was obtained by electrophoretic mobility measurements. Particle yield was calculated by an indirect method and the drug release profile was studied by a dialysis experiment. Results from PCS indicate that nanoparticles showed sizes of 300-400 nm, with a nearly monomodal size distribution. The zeta potential was found to be positive 25-30 mV. Particle yield was in the range of 30-50% and cisplatin was released in a sustained manner, in comparison with the starting alginate/cisplatin complex. Preliminary results from an in vitro nanoparticles have an inhibiting activity similar or even better than cisplatin on human A549 and A2780 and murine P388 cell lines.
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