Nano-in-nano containing curcumin and benzydamine hydrochloride for the treatment of Vulvovaginal Candidiasis: from development to biological application in vitro and in vivo

Abstract

Vulvovaginal candidiasis currently represents a major public health challenge due to its high incidence and reports of recurrences. These challenges are due to host-related factors, such as a compromised immune system, or pathogen-related factors, including resistance to antifungal agents, making it necessary to study new treatment alternatives, for example, substances of natural origin, such as curcumin (CUR). However, this substance presents problems that limit its therapeutic application, such as insolubility in aqueous solvents, which leads to low bioavailability. Despite this, the association of nanotechnology and drugs of plant origin proves to be a promising alternative to overcome the aforementioned limitations. Although this pathology is caused by a fungus, patients suffer a lot from the inflammation caused by it, therefore, this proposal aims to combine two drugs, benzydamine hydrochloride (anti-inflammatory) and curcumin (anti-fungal) in one system. nano-in-nano consisting of mesoporous silica nanoparticles (MSN) in a lipid structure (liposome). These two nanosystems were chosen to be combined in a hybrid system in order to combine characteristics such as chemical stability, versatility in the presence of pores, large surface area and hydroxyl groups of NSM with the high biocompatibility of the liposome. Among the different routes of administration, the vaginal route can be advantageous, as the vaginal mucosa has high permeability, high blood supply and lack of first-rate metabolism passage, optimizing the local action. Furthermore, the dispersion of the nano-in-nano system in thermo-responsive hydrogels would not only facilitate the application of the formulation in the vagina, since it is liquid at room temperature and gel at body temperature, but would also increase its residence time in the vagina environment, allowing sustained release at the specific site of action. (AU)