**1. Introduction**

Human skin exerts a pivotal function as a protection barrier against diverse exogenous noxious factors; however, it is exposed and undergoes diverse types of injuries, including burns, ulcers, trauma, lacerations, and acute or chronic wounds, which may compromise its integrity [1].

In this regard, when skin is damaged, a specialized and highly regulated dynamic process immediately takes place: wound healing [2]. The main goal of wound healing is to restore tissue integrity and to achieve homeostasis; however, this process may be complicated by distinct intrinsic and extrinsic factors [2]. Thus, in order to accelerate wound healing, a variety of wound dressings have been designed.

Irrespective of the type of wound, the main function of dressings is to aid in the repair of the wound through the reduction of pain and inflammation, to protect the damaged tissue from pathogenic agents, and to enhance cell differentiation and proliferation [3]. Although there several types of dressings which are commercially available, many of these present some drawbacks, such as an inefficient absorption of exudates, poor protection against infections by microbes, the lack of ability to maintain humidity, and the triggering of allergic effects [4]. In addition, several dressings may adhere to the wound and require constant changes, which may interfere with the granulation process and delay the healing course.

Therefore, in recent years, there has been increasing interest in asymmetric membranes as an alternative for designing wound dressings [5]. These types of membranes possess multiple advantages, such as structural similarity with the skin, an ability to absorb exudates due to their porous structure, and improved cell adhesion and proliferation [6,7]. Different polymers have been employed for their development, including chitosan, hyaluronic acid, collagen, poly vinyl alcohol (PVA), polycaprolactone (PCL), and alginate [8]. In particular, alginate is a biopolymer extracted from seaweed and has shown several unique properties, such as biodegradability, good hydrophilicity, and good biocompatibility [4]. Alginate has exhibited potential for improving wound healing due to its hemostatic properties; moreover, it may reduce microbial infections, enhance the absorption of exudates, and decrease allergic reactions [9]. These features render alginate an interesting option for wound dressings. In addition, alginate membranes possess the advantage that they may be functionalized with bioactive compounds that enhance their healing properties.

In this regard, curcumin is a natural compound that possesses a plethora of biological activities, including antimicrobial, antifungal, anti-inflammatory, and antioxidant effects [10–12]. In addition, curcumin improves wound healing, enhances epithelial regeneration, and increases the proliferation of fibroblasts [13,14]. Thus, curcumin could be a suitable pharmacological agen<sup>t</sup> for the elaboration of wound dressings. However, curcumin exhibits low bioavailability and is unstable in neutral and alkaline aqueous solutions, as well as in hydrophilic topical preparations [12,15]. These drawbacks could be overcome by a nanoparticle formulation that permits the controlled and gradual release of the compound.

Therefore, the objective of this study was to design and develop a novel wound dressing comprising an alginate membrane and PCL nanoparticles loaded with curcumin and stabilized with Pluronic® F-68 (CNp) for possible application in wound healing. The wound dressing was physicochemically characterized, and in vivo and ex vivo permeation assays were performed.

### **2. Materials and Methods**
