3.2.1. Swelling Test

From a practical point of view, the membranes should absorb the exudate from the wound and at the same time provide a moist environment that promotes healing. For this reason, the percentage of swelling of five different formulations was determined by weight difference (Figure 2).

**Figure 2.** Percentage of swelling in alginate membranes as a function of time. Effect on swelling capacity by the addition of PVA + glycerin (**M1**), PVA + glycerin + propylene glycol (**M2**), PVP + glycerin (**M3**), PVP + glycerin + propylene glycol (**M4**), and CNp + PVP + glycerin + propylene glycol (**CNp-M4**) (mean ± SE; *n* = 3). There were significant differences when ANOVA was applied at 5, 20, 30, and 60 min (*p* < 0.05).

Figure 2 depicts a di fference at a time of 20 min, when propylene glycol is added to the formulation with PVA (M2) in comparison to M1; however, there is no significant di fference between using or not using propylene glycol in the formulation combined with PVP (M3 and M4, respectively). In order to determine the di fferences in the percentage of swelling according to each formulation as a function of time, an ANOVA was performed. It was demonstrated that both the formulation and the time during which the membrane was exposed to PBS exerted a statistically significant e ffect on swelling with a 95% confidence level.

The formulation with the highest swelling value was M1, at 30 min (802.8 ± 76.0%), while the addition of propylene glycol (M2) decreased the swelling percentage after 10 min. On the other hand, M2 showed the lowest value in the swelling test before dissolving. The addition of propylene glycol to the polyvinyl alcohol mixture could increase the intermolecular interactions between both excipients via hydrogen bonds in the –OH groups, favored by a wide steric disposition, but could decrease the entry capacity of water molecules and their interaction with alginate by saturation, decreasing the swelling ability. In the case of the interaction of propylene glycol and PVP, the situation could be the opposite. The interaction of both excipients is lower, resulting in a lower swelling capacity of the alginate; i.e., the excipient that determines the majority of the response. This phenomenon is confirmed with the profile observed for CNp-M4 in relation to M4.

Namely, when water enters the polymer matrix, the chains begin to relax, giving rise to the opening of the polymer networks. This promotes the penetration of more water; however, in the last stages of swelling, the di ffusion coe fficient is diminished because the chains are completely relaxed and near equilibrium [30].

The membranes began to dissolve after being exposed to PBS for a longer period of time. According to the composition of the medium, polymers undergo degradation and erosion processes. When a polymer degrades, the chains are cleaved into oligomers and subsequently monomers. The continuous loss of monomers will eventually lead to the phenomenon of erosion, which progressively changes the microstructure of the membrane through the formation of pores [31]. The combination of these processes could favor the possible application of our M4 and CNp-M4 membranes as wound dressings, because it would not be necessary to remove them from the application site, avoiding harm through injury and discomfort to the patient.

Moreover, the level of exudate from a wound (for example, an ulcer) can vary from absent (dry ulcer) to minimally exuding (<5 mL fluid per 24 h), to moderately exuding (5 to 10 mL fluid per 24 h), and finally to highly exuding (>10 mL fluid per 24 h) [32]. In this regard, the measurement of the swelling capacity of a wound dressing developed with alginate could be classified as dressings of low absorbance (alginate wound dressing that absorbs less than 6 g of liquid per g of dressing, or less than 12 g/100 cm2), and dressings of high absorbency (an alginate wound dressing that absorbs 6 g or more liquid per g of dressing, or 12 g or more/100 cm2) [33]. With this consideration, CNp-M4 possesses a value of 17.48 g/100 cm2, corresponding to high absorbency and similar to several commercial products.

## 3.2.2. Mechanical Test

Wound dressings must be resistant and flexible for ease of handling [17]. Thus, the mechanical properties of the membranes are depicted in Figure 3. Formulations with PVA (M1 and M2) did not demonstrate a significant di fference in %E with 73.54 ± 0.87% and 74.90 ± 1.67%, respectively. TS was similar for M1, M2, and M3 samples with 1.32 ± 0.02, 1.34 ± 0.01, and 1.96 ± 0.05 MPa, respectively. By way of comparison, M1 and M2 membranes exhibited a lower TS and %E than the remaining formulations, probably due to PVA being a polymer that has been characterized as possessing poor elasticity, a rigid membrane, and low hydrophilic characteristics [34].

**Figure 3.** Effect of plasticizers on the mechanical properties of alginate membranes. Effect on mechanical properties by the addition of PVA + glycerin (M1), PVA + glycerin + propylene glycol (M2), PVP + glycerin (M3), PVP + glycerin + propylene glycol (M4), and CNp + PVP + glycerin + propylene glycol (CNp-M4), respectively. (**a**) Elongation at break; (**b**) tensile stress, (mean ± SD; *n* = 3). \* indicates *p* < 0.05 as statistically significant.

The %E and TS ofM3 were 68.63±6.75% and 1.18±0.07MPa, respectively; these values significantly increased with the addition of propylene glycol (M4), to 120.01±5.97% and 1.96 ± 0.05 MPa, respectively. M4 exhibited the highest values in the assay and showed a significant difference with respect to the remaining formulations without CNp. This may be explained, at least in part, by the properties of propylene glycol, which is a plasticizer with a small molecular weight that is able to create multiple H-bonds with PVP and SA chains into a package and, consequently, aid in the formation of cross-linked networks [35].

Therefore, because of its greater swelling capacity and better mechanical properties, the M4 membrane (a mixture of sodium alginate, PVP, and propylene glycol) was chosen for the incorporation of CNp.

On the other hand, the mechanical properties of M4 were modified when CNp dispersion was added to the formulation. The %E of CNp-M4 showed the highest value, with 144.39 ± 14.52%; in contrast, TS decreased to 1.52 ± 0.16 MPa. This could be due to the addition of CNp dispersion to the formulation decreasing the number of hydrogen bonds between the polymer molecular chains; as a result, less strength is necessary to break the membrane [36]. In comparison, CNp-M4 showed the highest %E, which could be due to the effect of Pluronic® F-68. The latter is a surfactant that decreases the pore number, providing a membrane with a homogeneous structure; thus, it is more resistant to changes, rendering higher elasticity properties.

### 3.2.3. Thermogravimetric Analysis (TGA)

It is important to determine the thermal properties of a substance, because these provide useful information for their identification and the characterization of materials. In Figure 4, thermograms of curcumin, CNp, M4, and CNp-M4 membranes are presented. For curcumin, mass loss was observed at 173 ◦C by TGA (Figure 4a); due to the degradation of turmeric powder, water loss was not observed, possibly due to its high hydrophobicity [37]. The weight loss of CNp started at approximately 90 ◦C, corresponding to dehydration, and there was a second plateau from 280 to 350 ◦C, suggesting a better thermal stability for curcumin when it is inside PCL nanoparticles than when alone. However, CNp lost more weight in a smaller temperature range.

**Figure 4.** Thermal analysis of nanoparticle-coated alginate membrane using (**a**) thermogravimetric analysis (TGA) and (**b**) differential scanning calorimetry (DSC). The thermal properties of the M4 membrane, CNp-M4 membrane, CNp, and curcumin are represented as a, b, c, and d, respectively.

On the other hand, in the M4 membrane, the first mass loss occurred between 90 and 240 ◦C, whereas for the CNp-M4 sample, weight loss began between 100 and 240 ◦C. This could be due to the evaporation of water traces, the degradation of propylene glycol, PVP, glycerin (150-220 ◦C), and turmeric powder [38]. In the case of the CNp-M4 membrane, it presented a slighter weight loss compared to the M4 membrane. The second mass loss of both samples was between 270 and 425 ◦C; in this stage, the decomposition of the functional groups of SA polymer chains is presented. Finally, the last plateau in M4 and CNp-M4 membranes started at 425 ◦C, which corresponds to the degradation of the SA backbone [19]. In the same manner, the CNp-M4 membrane thermogram revealed a lower weight-loss temperature compared with that of CNp; this is probably because membrane formulation is a mixture that contains more substances than CNp. This is similar to the thermal behavior exhibited by curcumin and CNp.

### 3.2.4. Differential Scanning Calorimetry (DSC)

DSC is a technique used to determine the quantity of heat either absorbed or released when substances undergo physical or chemical changes [39]. In Figure 4b, DSC thermograms of curcumin, CNp, M4 membrane as vehicle, and CNp-M4 membrane are presented. The melting point of curcumin was found to be 174 ◦C (Table 2), which was expected with regard to the literature [40]. Furthermore, three thermal events were observed in the CNp: at 63.5; 101, and 212 ◦C. The first thermal event could correspond to the melting point of PCL (61 ◦C) [41], while events at 101 and 212 ◦C may indicate the presence of trehalose, which was employed as a cryoprotectant to lyophilize the CNp [42]. Interestingly, the melting point of curcumin was not detected in the CNp sample; this could be due to the high EE of curcumin inside PCL nanoparticles as a molecular dispersion.


**Table 2.** Thermal events of curcumin, CNp, and alginate membranes by DSC.

On the other hand, both M4 and CNp-M4 membranes revealed two thermal events. The first peak was around 87 ◦C for both formulations, whereas the second peak was around 233 ◦C for the M4 membrane and 249 ◦C for the CNp-M4 membrane. The latter peaks were due to the presence of SA in the formulation. A thermal peak prior to 100 ◦C was observed for both samples, possibly due to the presence of water in the membranes.
