Effect of Organic-Phase Solvents on Physicochemical Properties and Cellular Uptake of Astaxanthin Nanodispersions

Abstract

A simplex centroid mixture design was used to study the interactions between two chosen solvents, dichloromethane (DCM) and acetone (ACT), as organic-phase components in the formation and physicochemical characterization and cellular uptake of astaxanthin nanodispersions produced using precipitation and condensation processes. Full cubic or quadratic regression models with acceptable determination coefficients were obtained for all of the studied responses. Multiple-response optimization predicted that the organic phase with 38% (w/w) DCM and 62% (w/w) ACT yielded astaxanthin nanodispersions with the minimum particle size (106 nm), polydispersity index (0.191), and total astaxanthin loss (12.7%, w/w) and the maximum cellular uptake (2981 fmol/cell). Astaxanthin cellular uptake from the produced nanodispersions also showed a good correlation with their particle size distributions and astaxanthin trans/cis isomerization ratios. The absence of significant (p > 0.05) differences between the experimental and predicted values of the response variables confirmed the adequacy of the fitted models.

Effects of homogenization process parameters on physicochemical properties of astaxanthin nanodispersions prepared using a solvent-diffusion technique

“…The cellular astaxanthin was extracted three times using methanol/ dichloromethane (1:1, v/v) and quantified by HPLC. 4 experimental design and data analysis…”

“…The final reduced models were obtained by removing the statistically nonsignificant (P0.05) terms, however, the nonsignificant (P0.05) linear terms with significant interaction or quadratic terms were kept in the final reduced models. 3,4 Numerical individual and multiple optimization procedures were performed using the response optimizer procedure in the software to predict the exact optimum levels of two independent homogenization factors leading to the overall preferred response goals. Verification of the models was done by comparing the experimental data with the values predicted by the final reduced models, 4 and the astaxanthin nanodispersions recommended for single and multiple optimization procedures were prepared and evaluated in terms of the studied physicochemical characteristics ( Table 2).…”

“…Moreover, the imperfect water solubility/dispersibility of astaxanthin has hampered its usefulness. [3][4][5] Even with the numerous recognized advantages of nanosized delivery systems, preparation of astaxanthin nanodispersions has not yet been demonstrated.…”

“…3,4 Nanodispersions are non-equilibrium complicated systems; however, because they have relatively high kinetic stability, they approach thermodynamic stability. These systems are composed of fine dispersed nanoparticles ranging in size from 20-200 nm in a continuous phase.…”

“…The solvent diffusion technique has been widely used for the preparation of functional bioactive lipid compounds. 4,6 This technique involves the dissolution of a lipophilic compound in a partially water-miscible organic solvent, for example, tetrahydrofuran, acetone, ethanol, or a mixture of water-miscible and water-immiscible solvent. 7 A large amount of water is then applied to the system to change the continuous phase nature (from organic solvent to water) and produce the nanodispersion system.…”