Usually caused by Candida albicans, buccal candidiasis begins with the morphological transition between yeast and hyphal cells. Over time and without the correct treatment, it can be disseminated through the bloodstream becoming a systemic infection with high mortality rates. C. albicans already shows resistance against antifungals commonly used in treatments. Therefore, the search for new drugs capable of overcoming antifungal resistance is essential. Histatin 5 (Hst5) is an antimicrobial peptide of the Histatin family, that can be found naturally in human saliva. This peptide presents high antifungal activity against C. albicans. However, Hst5 action can be decreased for interaction with enzymes and metal ions present in the oral cavity. The current work aims to bring a brief review of relevant aspects of the pathogenesis and resistance mechanisms already reported for C. albicans. In addition, are also reported here the main immune responses of the human body and the most common antifungal drugs. Finally, the most important aspects regarding Histatin 5 and the benefits of its interaction with metals are highlighted. The intention of this review is to show the promising use of Hst5 metallopeptides in the development of effective drugs.

Currently 75–88% of fungal infections are caused by Candida species, and Candida albicans is the main microorganism that causes these infections, especially oral candidiasis. An option for treatment involves the use of the antifungal peptide Histatin 5 (Hst 5), which is naturally found in human saliva but undergoes rapid degradation when present in the oral cavity, its site of action. For this reason, it is important to develop a way of applying this peptide to the oral lesions, which promotes the gradual release of the peptide. In the present study, we have evaluated the development of liposomes of different lipid compositions, loaded with the peptide as a way to promote its release slowly and gradually, preserving its antifungal potential. For this, the peptide 0WHistatin 5, an analog of the peptide Hst 5, was synthesized, which contains the amino acid tryptophan in its sequence. The solid phase synthesis method was used, followed by cleavage and purification. The liposomes were produced by thin film hydration technique in three different lipid compositions, F1, F2, and F3 and were submitted to an extrusion and sonication process to standardize the size and study the best technique for their production. The liposomes were characterized by dynamic light scattering, and tests were performed to determine the encapsulation efficiency, release kinetics, stability, and evaluation of antifungal activity. The extruded liposomes presented average size in the range of 100 nm, while sonicated liposomes presented a smaller size in the range of 80 nm. The encapsulation efficiency was higher for the sonicated liposomes, being 34.5% for F1. The sonicated F3 presented better stability when stored for 60 days at 4°C. The liposomes showed the ability to release the peptide for the total time of 96 h, with the first peak after 5 h, and a further increase of the released after 30 h. Time-kill assay showed that the liposomes were able to control yeast growth for 72 h. The data suggest that the liposomes loaded with 0WHistatin 5 maintained the action of the peptide and were able to limit the growth of C. albicans , being a suitable system for use in the treatment of oral candidiasis.

Candida albicans is a common microorganism of human’s microbiota and can be easily found in both respiratory and gastrointestinal tracts as well as in the genitourinary tract. Approximately 30% of people will be infected by C. albicans during their lifetime. Due to its easy adaptation, this microorganism started to present high resistance to antifungal agents which is associated with their indiscriminate use. There are several reports of adaptive mechanisms that this species can present. Some of them are intrinsic alteration in drug targets, secretion of extracellular enzymes to promote host protein degradation and efflux receptors that lead to a diminished action of common antifungal and host’s innate immune response. The current review aims to bring promising alternatives for the treatment of candidiasis caused mainly by C. albicans. One of these alternatives is the use of antifungal peptides (AFPs) from the Histatin family, like histatin‐5. Besides that, our focus is to show how nanotechnology can allow the application of these peptides for treatment of this microorganism. In addition, our intention is to show the importance of nanoparticles (NPs) for this purpose, which may be essential in the near future.

Some diseases of uncontrolled proliferation such as cancer, as well as infectious diseases, are the main cause of death in the world, and their causative agents have rapidly developed resistance to the various existing treatments, making them even more dangerous. Thereby, the discovery of new therapeutic agents is a challenge promoted by the World Health Organization (WHO). Biomacromolecules, isolated or synthesized from a natural template, have therapeutic properties which have not yet been fully studied, and represent an unexplored potential in the search for new drugs. These substances, starting from conglomerates of proteins and other substances such as animal venoms, or from minor substances such as bioactive peptides, help fight diseases or counteract harmful effects. The high effectiveness of these biomacromolecules makes them promising substances for obtaining new drugs; however, their low bioavailability or stability in biological systems is a challenge to be overcome in the coming years with the help of nanotechnology. The objective of this review article is to describe the relationship between the structure and function of biomacromolecules of animal origin that have applications already described using nanotechnology and targeted delivery.