Abstract:
Chitosan-coated alginate nanoparticles containing dacarbazine were prepared by ionotropic pre-gelation of alginate with calcium chloride followed by complexation between alginate and chitosan. Six formulations using three concentrations of dacarbazine (1, 2 and 5 mg) and two different molecular weight and percent deacetylation of chitosans (MW 15000 Da, 90% deacetylation and MW 100000 Da, 95% deacetylation) were studied. The obtained nanoparticles were spherical. Alginate nanoparticles containing 1, 2 and 5 mg dacarbazine which were coated with 15000 Da chitosan and those which were coated with 100000 Da chitosan had the particle sizes of 489.03 ± 2.39, 538.33 ± 5.69, 556.90 ± 10.55, 548.67 ± 7.51, 559.00 ± 6.56 and 584.77 ± 17.18 nm, respectively with the polydispersity index of 0.57 ± 0.03, 0.30 ± 0.01, 0.54 ± 0.03, 0.38 ± 0.01, 0.42 ± 0.06 and 0.41 ± 0.03, respectively and the zeta potential values of -28.13 ± 0.40, -28.30 ± 0.53, -28.97 ± 0.15, -28.03 ± 0.29, -28.03 ± 0.47 and -28.07 ± 0.21 mV, respectively. The results showed that the mean particle size of dacarbazine chitosan-coated alginate nanoparticles increased when the amount of drug increased. The negative value of zeta potential increased independently on the amount of drug, whereas the molecular weight of chitosan did not influence to the zeta potential. The entrapment efficiency of alginate nanoparticles containing 1, 2 and 5 mg dacarbazine which were coated with 15000 Da chitosan and of those which were coated with 100000 Da chitosan were 38.19 ± 0.84 %, 40.14 ± 0.35 %, 31.36 ± 1.14 %, 39.21 ± 0.56 %, 41.55 ± 0.49 % and 33.34 ± 1.46 %, respectively. The obtained nanoparticles which contained 2 mg of dacarbazine coated with chitosan either 15000 Da or 100000 Da showed the highest percentage of entrapment efficiency. The stability in pH 3-4 citric acid solution and in normal saline solution, either at room temperature or at 2-8ºC of dacarbazine in chitosan-coated alginate nanoparticles was better than that of free dacarbazine up to 72 hours of storage.