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Molecules 2019, 24, x Molecules 2019, 24, 1388 5 of 14 (B) zeta potential, (C) encapsulation efficiency (%), and (D) loading capacity (%). Table 3. Significance (p < 0.05) of the factors in the generated models. ® X2 (TweenX 80(CcSo/nAclegnmtrastsiornat)io) X3 (CS/Alg mass ratio) <00.2.0301051 <0.0001 <0.000.10218 0.0015 0.2860.0023 3 <0.0001 0.0015 0.0023 Table 3 Significance (p < 0.05) of the factors in the generated models. 5 of 14 (C) (D) Figure 1. Representative response surface plots showing the effect of the formulation factors (curcumin Figure 1. Representative response surface plots showing the effect of the formulation factors concentration, Tween® 80 conce®ntration, and CS/Alg mass ratio) on the (A) particle size, (B) zeta (curcumin concentration, Tween 80 concentration, and CS/Alg mass ratio) on the (A) particle size, potential, (C) encapsulation efficiency (%), and (D) loading capacity (%). Factors Factors Y1 Y2 Y3 Y4 Y1 Y2 Y3 Y4 X1 (Curcumin concentration) X1 (Curcumin con®centration) (Particle size) 0.3544 Zeta potential (EE) 0.9619 0.0062 0.0001 X2 (Tween 80 concentration) 0.3544 0.2315 0.9619 0.0062 0.0218 0.2860 0.4089 (Particle size) Zeta potential (EE) (LC) (LC) 0.0001 0.4089 The curcumin concentration had a significant synergistic effect on the EE and LC. Fattahpour et al. [23] suggested that the drug concentration was the main driving force in drug entrapment in NPs. al. [23] suggested that the drug concentration was the main driving force in drug entrapment in NPs. On the other hand, the curcumin concentration had no significant effect on the particle size and zeta On the other hand, the curcumin concentration had no significant effect on the particle size and zeta potential. A possible explanation for this is that the hydrophobic nature of curcumin results in drug potential. A possible explanation for this is that the hydrophobic nature of curcumin results in drug loading in the NPs being mainly through physical entrapment since curcumin offers no significant loading in the NPs being mainly through physical entrapment since curcumin offers no significant electrostatic interactions with the chitosan (CS) and alginate (Alg) polar groups that could affect the electrostatic interactions with the chitosan (CS) and alginate (Alg) polar groups that could affect the polymer cross linking and surface charge density [24]. The curcumin concentration had a significant synergistic effect on the EE and LC. Fattahpour et polymer cross linking and surface charge density [24]. The Tween® 80 concentration had no significant effect on the particle size, EE, and LC, but based The Tween® 80 concentration had no significant effect on the particle size, EE, and LC, but based on Equation (2), it had a significant synergistic effect on the zeta potential, where a less negative on Equation (2), it had a significant synergistic effect on the zeta potential, where a less negative zeta zeta potential was observed with higher Tween® 80 concentrations. Lertsutthiwong et al. [25] also potential was observed with higher Tween® 80 concentrations. Lertsutthiwong et al. [25] also suggested that being amphiphilic, Tween® 80 can interact with curcumin by its hydrophobic tail suggested that being amphiphilic, Tween® 80 can interact with curcumin by its hydrophobic tail and and with Alg by its hydrophilic head. It is possible that binding of Tween® 80 with the Alg shell with Alg by its hydrophilic head. It is possible that binding of Tween® 80 with the Alg shell following following crosslinking with CaCl2 resulted in a reduced surface charge density, leading to a less crosslinking with CaCl2 resulted in a reduced surface charge density, leading to a less negative zeta negative zeta potential. potential. The CS/Alg mass ratio had a significant effect on the Cur-CS/Alg NP size and a significant The CS/Alg mass ratio had a significant effect on the Cur-CS/Alg NP size and a significant antagonistic effect on the zeta potential, EE, and LC. The formation of Cur-CS/Alg NPs involves the antagonistic effect on the zeta potential, EE, and LC. The formation of Cur-CS/Alg NPs involves the spontaneous electrostatic interaction between the negatively charged carboxylate groups on Alg and spontaneous electrostatic interaction between the negatively charged carboxylate groups on Alg and the positively charged protonated amino groups on CS [26]. The use of a higher CS/Alg mass ratio the positively charged protonated amino groups on CS [26]. The use of a higher CS/Alg mass ratio results in a better formation of the CS network on the surface of the CaCl2-Alg shell, leading to the results in a better formation of the CS network on the surface of the CaCl2-Alg shell, leading to the production of larger sized NPs. For this study, a particle size of 200 to 300 nm was desired, since it production of larger sized NPs. For this study, a particle size of 200 to 300 nm was desired, since it has been demonstrated that NPs in this size range are capable of penetration, localization, and drug has been demonstrated that NPs in this size range are capable of penetration, localization, and drug diffusion into the layers of the skin [24]. From the results, it was found that the use of low to medium CS/Alg mass ratios produced NPs within the desired size range.PDF Image | Synergistic Effects of Photo-Irradiation and Curcumin-Chitosan
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