1.1 Introduction
The use of biodegradable materials in the formulations of products for skin application has been carried out since the eighteenth century. This area is becoming even more popular with the development of innovative and cutting-edge materials with improved biodegradability and higher skin compatibility.
Cosmetic and galenic formulations for topical application allow a local action and may avoid penetration of active pharmaceutical ingredients (APIs) into the bloodstream. In certain cases, this strategy is desirable to avoid the systemic effects of powerful APIs, which cannot be achieved with oral and parenteral administration. Therefore, topical administration is able to maintain the therapeutic level of the bioactive in the site of action and reduce the administration frequency. Topical administration of APIs can have cosmetic or pharmaceutical purposes. Generally, formulations with cosmetic purposes are used for aesthetic reasons, for example, to modify the appearance of the skin, and to protect and clean the skin. Pharmaceutical formulations are those that cure, treat, mitigate/prevent disease or affect the structure or function of the human body to treat or cure some pathology. Due to the systematic combination of both in the same product, the term more appropriately adopted is “cosmeceutical” product, which has the major goals of improving skin condition and health. However, the Federal Food, Drug, and Cosmetic Act does not recognize this terminology, and the cosmetic industry uses the term “cosmeceutical” to refer to cosmetic products that have medicinal or drug-like benefits. Additionally, drugs are subject to a review and approval process by the Food and Drug Administration (FDA), while cosmetics are not approved (FDA, 2014).
The APIs mostly applied in cosmetic formulations include depigmenting agents (Leelapornpisid et al., 2010; Dadzie and Petit, 2009), antioxidants (Leelapornpisid et al., 2010; Gokce et al., 2012), skin renewal agents (Dashora, 2013), ultraviolet (UV)-blockers, and sunscreens (Severino et al., 2012b; Souto et al., 2005). The most common APIs delivered by pharmaceutical formulations to the skin include corticosteroids (Ramsing and Agner, 1995), retinoids (Moon et al., 1997), antimicrobial and antimycotic agents (El-Badry et al., 2014; Sahoo et al., 2014; Verma et al., 2014), immune-suppressants (Euvrard et al., 2004), anesthetics (Pathak and Nagarsenker, 2009), and antipruritic agents (Wahlgren et al., 1990).
The advantages of using nanobiomaterials for skin delivery and targeting rely on the use of non-toxic, biodegradable, and biocompatible materials, with rapid and reversible onset of action, and that are pharmacologically inert (Souto et al., 2011, 2013). Additionally, nanobiomaterials enable an increase in bioactive skin exposure, decreasing the necessity for treatment frequency (Simeonova et al., 2003).
1.2 Skin as Site for Topical Delivery
The skin is the largest body organ and, due to its large area, remains an attractive site for the delivery of APIs (Souto and Müller, 2008). The skin is responsible for various functions, such as sensitivity, physical protection, immunological and microbiological control, temperature regulation, prevention of excessive water loss, and production of vitamin D. The human skin is composed of cells and cutaneous annexes (hair follicles, nails, and gland), and can be divided into three basic layers: the epidermal layer (the outer most layer, populated mostly by keratinocytes), the dermal layer (consisting of two regions, the papillary dermis and reticular dermis), and the hypodermis or subcutaneous fat layer (mostly composed of fibroblasts, adipose cells, and macrophages) (Mikesh et al., 2013).
Briefly, the epidermis (50–100 μm in thickness) is composed of epithelial cells distributed in layers which, from inside to outside, are classified as germinal or basal, spinous, and granular corneal layers, respectively. In the palmar and plantar regions, between the cornea and granulosa layers, lies the lucid layer (WHO, 2009). The germ layer gradually reaches the surface, undergoing changes in form and chemical composition to become anucleate, composing the stratum corneum (SC) and forming the outermost layer of the epidermis. The region below the SC, in which the cells proliferate and undergo changes, gives rise to dead cells of the SC, and is called viable epidermis (Venus et al., 2010).
The dermis (1–2 mm in thickness) is the tissue located beneath the epidermis. This layer is composed of glands, nerve endings, blood vessels, some cell types such as fibroblasts, collagen, and elastin fibers. The deepest layer is the hypodermis, with variable thickness and mostly formed by adipocytes (Zhai and Zhai, 2014).
The topical administration of galenic and cosmetic formulations based on nanobiomaterials seems to have high efficiency due to the large surface area of skin contributing to their adhesiveness, occlusion, and hydration capacity (Alvarez-Román et al., 2004). Therefore, it is necessary to consider physicochemical properties, such as zeta potential, polydispersity index, size, type of nanomaterial, loading efficiency, and administration route (Desai et al., 2010).
Depending on the effect required for a certain API, that is, local (epidermis) or systemic (dermis), its permeation could be modulated. Formulations for cosmetic purposes can only exert local action/effect in the skin surface such as make-up, film formers, sunscreens, insect repellents, antimicrobials, and antifungals. Other treatments include the interactions with the SC, which are related to the softness and stimulation of keratosis (keratolytic effect). In this case, it is expected that these substances do not reach the viable epidermis, because they should only affect the outermost layer of the skin, in contrast to bioactive substances such as anti-inflammatory, anesthetic, antipruritic, cytotoxic, and immunosuppressive agents, which should be able to reach the viable epidermis and dermis. Beside the skin layers, there are situations where substances need to target the skin appendages, such as glands (sebaceous and eccrine) and hair follicles (Schoellhammer et al., 2014).
The skin provides immunological, physical, and UV protection (Salmon et al., 1994). The first barrier of the skin, namely the SC, is highly impermeable mainly due to two factors: (1) SC is composed of keratinocytes which are arranged in a scaffold-like lattice, bound together by the fibrous proteins and (2) the intercellular spaces are filled with a lipid-rich matrix arranged in a laminar structure providing a robust and waterproofing barrier (Venus et al., 2010).
The immunological protection is provided by some of the cells that compose the skin and are responsible for defense against microorganisms. The mechanisms include (1) the production of antimicrobial peptides, which kill Gram-positive and Gram-negative organisms, fungi, and some viruses; (2) resident epidermal Langerhans cells that act as antigen-presenting cells; and (3) transient epidermal T-cells that protect against pathologies such as dermatitis, bullous disord...