## 3 Nanosized-Lipid-Based Drug Delivery Systems in Wound Healing  
The skin has a crucial role in maintaining body fluids homeostasis, thermoregulation and preventing microorganism penetration. Several skin wounds may present different needs in terms of treatment due to the difference in each pathophysiology. Regarding acute burn wounds, not only are the skin structures damaged, but all the systems are affected due to the leakage of plasma into interstitial spaces, which can also lead to hypovolemic shock, depending on the extension of the burn. Moreover, the affected skin barrier increases the susceptibility to bacterial infection. Therefore, in the management of burn wounds, an imperative goal is to prevent infections and enhance reepithelial in order to preserve skin functionality [46]. Most efforts have been focused on the antimicrobial activity of topical agents, which have failed in front of the increased antibiotic resistance rate [47]. Thus, a wide range of nanosized-lipid-based delivery systems such as liposomes [48; 49; 50], transfersomes [51], ethosomes and lipid nanoparticles [52] has been explored to overcome infections and enhance skin regeneration in burn wounds, with promising results. In open wounds such as lacerations, where the underlying tissues are cut by shargped-edged instruments, the imperative treatment is to clean the wound and remove any foreign bodies or dead tissue [53]. Chronic wounds are associated with an impaired repair process prolonged for more than three months [10], produced by an extended inflammation phase, persistent infections, impaired angiogenesis or a high amount of reactive oxygen species. The most common ones are non-healing ulcers caused by venous insufficiency or diabetes [54]. Current treatments in chronic wounds focus on nanoparticles containing dressings that can maintain a suitable moist environment, prevent infection and promote the wound-healing process. Progress in nanosized-lipid-based drug delivery systems has led to new treatments in chronic wounds, increasing the half-time and bioavailability of the drugs and reducing the cost, the toxicity and the number of applications [54]. Several molecules, such as all-trans retinoic acid [55], 20(5)-protopanaxadiol [56], epidermal growth factor (EGF), curcumin [57], phenytoin [58] and tumor necrosis factor \(\alpha\)[59], have been encapsulated in several nanosized-lipid-based  
Figure 2: The structure of nanosized-lipid-based drug delivery systems applied in wound care: (**a**) conventional liposomes, (**b**) transfersomes, (**c**) ethosomes, (**d**) solid lipid nanoparticles and (**e**) nanostructured lipid carriers. drug delivery systems to treat wounds associated with diabetes, with promising effects for different wound healing phases. Lipid nanoparticles could be more suitable in burn wounds and chronic wounds due to their occlusive effect on the stratum corneum, which can avoid transepidermal water loss and keep the wound hydrated. In addition, the nanostructured lipid carriers are presented as better nano-delivery systems compared with vesicular systems. They exhibit excellent stability, low toxicity, high drug loading capacity and sustained drug release, which can help reduce the number of drug administrations and the wound's healing time [60, 61]. Surgical wounds are predisposed to an increased inflammatory reaction due to suture materials, which can lead to infections, hematomas or dehiscence. These effects prolong the wound-healing process and delay hospital discharge, increasing the costs and morbidity [62]. In this case, antimicrobial advanced wound dressings are suitable to treat the wounds [63]. Additionally, nanosized-lipid-based drug delivery systems showed promising results in treating excisional wounds in rats [52, 55, 56, 57, 64, 65]. Furthermore, surgical wounds may be followed by excessive collagen synthesis in the remodeling phase, leading to keeloid or hypertrophic scars [66].