Vitamin D3 (cholecalciferol) is a steroid hormone produced by the photolytic action of UV-B radiation on the 7-dehydrocholesterol molecule found in the epithelial tissue, producing pre-vitamin D3, which is absorbed and then metabolized in the liver to 25-hydroxyvitamin D3. The latter subsequently reaches the renal tubules and is converted into the active form, 1,25-dihydroxyvitamin D3 [1–3]. Evidence obtained in the laboratory indicates that the active hormonal form of vitamin D3 induces a range of extra-skeletal biological responses, in addition to its effects in bone metabolism, including regulation of skin cell proliferation, effects in the cardiovascular system, and protection against various autoimmune diseases, multiple sclerosis, cancer, obesity, and inflammatory intestinal disease [4, 5].
More recently, vitamin D3 has received increasing attention, because deficiency of this hormone has led to increasing cases of rickets, making it a global health issue. Epidemiological studies have found low levels of this vitamin throughout the global population, irrespective of age, level of education, or race [2, 6].
The three main factors involved in maintaining satisfactory levels of vitamin D3 are adequate consumption of foods rich in cholecalciferol, sufficient exposure to solar UV-B to permit transdermal synthesis of the hormone, and dietary supplementation . Populations that present inadequacy of one or more of these sources of vitamin D3 are at risk of deficiency . A difficulty is that oral ingestion methods can have limitations in individuals with intestinal disorders, Crohn’s disease, or chronic hepatic, gastric, and renal disorders. In these individuals, the intestinal absorption of this vitamin is compromised [8, 9].
The main risk factors for decreased serum levels of vitamin D3 include excessive use of sunscreens, living in closed environments, chronic use of drugs that reduce serum cholesterol and consequently decrease levels of 7- dehydrocholesterol in the skin, advanced age, distance from the equator, air pollution, black skin, smoking, and intestinal malabsorption syndromes, among others [3, 5, 10].
Vitamin D3 has low water solubility, so various formulations have been developed to increase its solubility, such as the use of liposomes, lipid emulsions, and mixed micelles [11–13]. However, these formulations are unstable, with degradation and oxidation easily occurring during storage. Therefore, further studies are needed of the incorporation of this hormone in new release systems [14, 15].
As an alternative to oral administration of vitamin D3, which may present low efficiency due to the various barriers and different conditions encountered, application to the skin can offer advantages such as the treatment of psoriasis, atopic dermatitis, and other allergic skin diseases .
Materials based on nanocellulose (NC) have the potential for use in the sustained release of cosmetics and drugs [17, 18]. In addition to systemic effects, the local release of drugs using materials based on NC has also been explored . The transdermal materials that have been developed, such as membranes, hydrogels, and microspheres, have been shown to enhance the efficacy of drugs, while reducing side effects [20, 21].
The market for nanocellulose was estimated to be worth US$250 million in 2019, while the number of scientific articles concerning the use of nanocellulose in medical and pharmaceutical applications has steadily increased over the last ten years . However, there is still a vast field open for the development of new innovations, such as using different functionalities and interactions of bioactive agents, employing functional nanocelluloses for the development of new drug delivery systems and cell culture media, as well as for tissue engineering and for combating bacteria and viruses .
Meanwhile, the number of such products marketed in the medical and pharmaceutical areas remains low, which can be attributed to challenges such as the development of formulations incorporating highly lipophilic or high molar mass drugs, stability during storage, quality control of the drugs, and other factors such as limited production for large batches. It is expected that nanomaterials will find uses in cosmetic products such as lotions, soaps, and skin treatments, as has been discussed at conferences and can be seen in the patent literature. Cosmetics companies have shown interest in bio-based nanomaterials that are biocompatible and biodegradable .
Many investigations have already been undertaken by researchers and companies, with the aims of optimizing the production and marketing of nanocellulose. Nanocellulose has a wide range of applications in the health area, which could contribute to addressing the multiple challenges of modern society. It could have significant future contributions in materials engineering and the attainment of global sustainable development goals .
The aim of the present work was to develop an innovative system for the sustained release of vitamin D3, employing a matrix of crystalline NC extracted from cotton linter. The development of a new nanostructured system for the sustained transdermal release of vitamin D3 could enable convenient treatment of various skin conditions, as well as provide appropriate supplementation of this hormone.