Mucoadhesive alginate synthesis: a multivariate calibration approach

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 X₁ type of alginate; X₂ quantity of EDAC; X₃ quantity of L-cysteine; X₄ reaction temperature and X₅ reaction time were studied along with two responses: Y₁ amount of thiol groups (–SH) and Y₂ disulfide bonds (–S–S–). A PLS quadratic model (P < 0.05) was obtained in the optimization step (R² = 0.851 and Q² = 0.570). A thiomer with a maximum amount of –SH groups of 503.87 μmol g⁻¹ and a minimum formation of –S–S– bonds 260.17 μmol 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 °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.