Abstract

A multivariate approach that consists of a two-step design of experiments and partial least squares regression (PLSR) calibration was performed in order to synthesize a thiomer based on alginate-cysteine mediated by carbodiimide (EDAC). Five processing variables X-1 type of alginate; X-2 quantity of EDAC; X-3 quantity of l-cysteine; X-4 reaction temperature and X-5 reaction time were studied along with two responses: Y-1 amount of thiol groups (-SH) and Y-2 disulfide bonds (-S-S-). A PLS quadratic model (P < 0.05) was obtained in the optimization step (R-2 = 0.851 and Q(2) = 0.570). A thiomer with a maximum amount of -SH groups of 503.87 mu mol g(-1) and a minimum formation of -S-S- bonds 260.17 mu mol g(-1) was obtained under the optimal synthesis conditions: quantity of EDAC 0.82 g; quantity of l-cysteine 3.00 g; reaction time 1.0 h; reaction temperature 10 degrees C; and using sodium alginate. The optimized thiomer showed the amount of -SH increased from 55 to 120% compared to previous reports on alginate-cysteine thiomers synthesized using the univariate method, and has elastic and viscous modulus more than 7-fold higher than the unmodified alginate obtained in in vitro mucoadhesive assays with mucin.