*2.1. Materials*

For CNp fabrication, we used PCL (Mn 80,000 g/mol), Pluronic® F-68, and trehalose dihydrate, which were purchased from Sigma-Aldrich® (Merck KGaA, Darmstadt, Germany), whereas methanol, ethyl acetate, and curcumin were supplied by Spectrum® (Spectrum Laboratory Products, CA, USA). For membrane elaboration and characterization, we employed sodium alginate [(SA) (300–700 cps 1.0%, RV, 20 rpm, 25 ◦C], glycerol (Gly), propylene glycol (Prop), and Tween 80, which were purchased from Droguería Cosmopolita (Mexico City, Mexico). PVA, Pluronic® F-127, acetone, and phosphate buffered saline (PBS) solution were supplied by Sigma-Aldrich® (Merck KGaA, Darmstadt, Germany). Kollidon® 30 [Polyvinylpyrrolidone k 30; (PVP k30)] was obtained from BASF (USA). Ethyl acetate was acquired from Distribuidora Química Alvi (State of Mexico, Mexico). Methanol was purchased from Fermont (Nuevo León, Mexico). All other chemicals and reagents were of at least analytical-grade quality.

#### *2.2. Preparation of PCL Nanoparticles Loaded with Curcumin (CNp)*

CNp were prepared by the emulsification–diffusion method, as previously described by Quintanar-Guerrero, et al. [16]. Briefly, the organic saturated phase and aqueous saturated phase were obtained by the saturation of an ethyl acetate and distilled water mixture at a 1:1 ratio. After that, 2% (*w*/*v*) solution of PCL was prepared by dissolving 400 mg of PCL in 20 mL of the organic saturated phase; once PCL was dissolved, 100 mg of curcumin was added. At the same time, 5% (*w*/*v*) of Pluronic® F-68 solution was prepared using an aqueous saturated phase as solvent. In order to obtain an emulsion, both solutions were mixed at a 1:2 ratio with a high-speed homogenizer (Ultra Turrax T18; IKA®) at 14,000 rpm for 10 min at room temperature. Then, 160 mL of water was added to the emulsion to generate polymer aggregation, and the system was maintained under the same conditions for 10 min. The organic solvent was evaporated by a rotary vacuum (Heidolph®, Schwabach, Germany), and the nanoparticle suspension obtained was centrifuged at 15,557 *g* for 30 min at 25 ◦C. Finally, the pellet was dissolved in distilled water. In order to assess the thermal stability and the properties of the nanoparticles, CNp were frozen and lyophilized at −49 ◦C, 0.05 mBar for 24 h, employing 5% *w*/*v* trehalose dihydrate as a cryoprotectant.

### *2.3. Physicochemical Characterization of CNp*

#### 2.3.1. Particle Size and Zeta Potential Assessment

The particle size and distribution (polydispersity index, PDI) of the CNp were evaluated by dynamic light scattering. On the other hand, to determine the Zeta potential of CNp, laser Doppler velocimetry was employed. CNp dispersions were assessed five times at 25 ◦C in a Zetasizer (Malvern Instrument ZS90; Malvern, UK).

### 2.3.2. Atomic Force Microscopy (AFM)

CNp size and geometry were analyzed by atomic force microscopy (AFM) with a scanning probe microscope (JSPM-4210, JEOL®, Tokyo, Japan). In brief, the CNp dispersion was obtained after centrifugation, and the pellet resuspension was diluted to 1:100 with distilled water. A drop was placed on a coverslip, allowing it to dry at room temperature. The coverslip with the drop was held in place with carbon tape, and room-temperature conditions were utilized to assess the samples.

#### 2.3.3. Drug Loading and Entrapment Efficiency of CNp

To calculate entrapment efficiency (EE) and drug loading (DL), the CNp dispersion was centrifuged at 15,557 *g* for 40 min; then, the sediment was resuspended in ethyl acetate and the absorbance was measured by UV–Vis spectrophotometry at 420 nm (DLAB ®, SP-UV1000, Beijing, China). The amount of curcumin was obtained by interpolation in a calibration curve ( *R*<sup>2</sup> coe fficient = 0.99985).

The percentages of EE and DL were calculated from the equations below:

$$\% \text{EE} = \frac{\text{CN}}{\text{IC}} \times 100\tag{1}$$

$$\% \text{ DL} = \frac{\text{CN}}{\text{N}} \times 100 \tag{2}$$

where CN = the amount of curcumin in nanoparticles, IC = the initial amount of curcumin, and N = the number of nanoparticles.

### *2.4. Preparation of Polymer Gels and Membranes*

Four membrane formulations based on SA (M1, M2, M3, and M4) (See Table 1) were prepared using the solvent casting method as published by Karki et al. [17]. First, SA and the polymer were dissolved separately in injectable water by stirring at 35 ◦C. After dissolution, they were mixed with each other by mechanical stirring. Then, the plasticizer (or a plasticizer mixture) was added by stirring at room temperature until a homogeneous gel was obtained. In order to eliminate bubbles from the gel, it was centrifuged at 636 *g* for 20 min at room temperature (BIOBASE, BKC-TH18II, Shandong, China).

**Table 1.** Formulation of alginate membranes with di fferent polymers as plasticizers. PVA: poly vinyl alcohol; PVP: polyvinylpyrrolidone; CNp: polycaprolactone (PCL) nanoparticles loaded with curcumin.


In order to obtain the membranes, 10 g of each gel, prepared with the previously mentioned methodology, was poured into a Teflon cast 12 cm in diameter and left to dry into an oven (OAKTON Stable Temp, IL, USA) at 75.0 ± 0.5 ◦C for 3 h.

#### 2.4.1. Preparation of Nanoparticle-Coated Alginate Membranes (CNp-M4)

The methodology described previously was followed to prepare our nanoparticle-coated alginate membrane (CNp-M4), but the vehicle utilized was a dispersion of CNp to obtain 0.01% *w*/*v* of curcumin instead of injectable water. In order to prepare the membranes, the gel obtained was poured into a Teflon cast and left to dry in an oven at 40.0 ± 0.5 ◦C for 4 h.

### *2.5. Physicochemical Characterization of Membranes*
