Skin and Wound Healing: Conventional Dosage versus Nanobased Emulsions Forms

Abstract

The skin plays a crucial role in the body's homeostasis through its thermoregulation functions, metabolic activity, and, mainly, its barrier function. Once this system has its homeostasis disturbed, through the promotion of tissue discontinuity, an injury happens and a restoration process starts. Different products can be used to promote, accelerate, or stimulate the healing process, such as hydrogels, emulsions, and ointments (main conventional formulations). Despite the historical use and wide market and consumer acceptance, new systems emerged for wound management with the main challenge to overcome conventional form limitations, in which nanosystems are found, mainly nanobased emulsion forms (nano- and microemulsions, NE and ME). Here, we discuss the skin function and wound healing process, highlighting the cellular and molecular processes, the different wound classifications, and factors that affect physiological healing. We also investigated the recent patents (2012-2023) filed at the United States Patent and Trademark Office, where we found few patents for conventional forms (hydrogels = 5; emulsions = 4; ointments = 6) but a larger number of patents for nanobased emulsions filed in this time (NE = 638; ME = 4,072). Furthermore, we address the use of nanobased emulsions (NE and ME) and their particularities, differences, and application in wound treatment. This work also discusses the challenges, bottlenecks, and regulatory framework for nanosystems, industrial, academic, and government interest in nanotechnology, and future perspectives about this key factor for the nanosystems market and consumer acceptance.

Figure 1

Skin is the border organ of the human body, being at the interface between the internal environment (systems and organs) and the external environment. Among its various relevant biological functions, its barrier action stands out, protecting the organism from external aggressions (physical, microbiological, and chemical), acting as an outside–inside barrier, preventing transepithelial water loss and dehydration, and acting as an inside–outside barrier.

Figure 2

The skin is a stratified tissue, with its basic structures being the epidermis, dermis, hypodermis, or subcutaneous tissue. The epidermis, the outermost layer of the tissue, is mainly responsible for the barrier function and protection against external aggressions. This layer can also be divided into other strata according to the degree of keratinization of the keratinocytes and other intrinsic characteristics, namely, stratum basale, stratum spinosum, stratum granulosum, stratum lucidum, and stratum corneum, with the first three strata known as viable epidermis. The dermis, a layer intimately connected to the epidermis by the dermoepidermal junction, is home to the cutaneous appendages (hair follicles, sweat glands, sebaceous glands, blood and lymphatic vessels, and the neurovascular component of the skin). The dermis is responsible for the support and flexibility of the skin. Ke, keratin; Ep, epidermis (keratinized stratified squamous epithelium); PaD, papillary dermis (loose connective tissue); ReD, reticular dermis (dense irregular connective tissue). The histological section (hematoxylin and eosin-stained sections of human skin) was obtained by the Laboratory of Morphological Sciences, Department of Morphological Sciences of the Biomedical Institute, Federal University of the State of Rio de Janeiro (UNIRIO).

Figure 3

Wound healing processes by (A) primary intention, (B) secondary intention, and (C) tertiary intention. First intention healing is characteristic of surgical processes, where at the end of the procedure, there is a juxtaposition of the edges of the incision made through suturing, for example, favoring a “clean” healing process. Healing by secondary intention is associated with a healing process that occurs organically; that is, it goes through all phases and normal healing processes (coagulation and hemostasis, inflammatory, proliferative, and remodeling phases), culminating in the end in a keloid-looking scar. Finally, healing by third intention consists of a natural wound healing process interrupted after the formation of granulation tissue and surgically corrected to accelerate healing and provide a better aesthetic appearance, for example.

Figure 4

Main blood and immune cell types that participate in wound healing in the different phases of the healing process (coagulation and hemostasis, inflammatory, proliferative, and remodeling phases). Initially, platelets form a platelet plug to prevent too much blood loss. This process occurs on the scale of minutes. Neutrophils, the most abundant leukocyte in the blood, are the first cell type of the immune system to migrate to the injury site and begin the inflammatory phase of healing. Macrophages migrate secondarily and are critical cells in the progression of healing to the proliferative phase. Finally, T lymphocytes migrate at the end of the inflammatory phase and remain at the injury site until the healing process ends.

Figure 5

The physiological healing process can be affected by local or systemic factors that make the healing of an injury difficult. The presence of foreign bodies, infection, and low oxygenation are examples of local factors. At the same time, age and gender, sexual hormones, stress, associated diseases such as diabetes and obesity, nutritional status, immune system status, and lifestyle habits, such as a sedentary lifestyle, alcoholism, and smoking are categorized as systemic factors, as they affect the individual’s overall health, as well as the ability of healing mechanisms to resolve the injury.