# A New In Vitro Model to Evaluate Anti-Adhesive Effect against Fungal Nail Infections
## 1 Introduction
The infected organism then migrates through the underlying nail matrix, resulting in mild inflammation, focal parakeratosis and subungal hyperkeratosis with two possible consequences: detachment of the nail plate from the nail bed and thickening of the sub-unitary region. This way, a subungual space is formed, which can serve as a reservoir for a superinfection of bacteria and molds, giving the plaque a yellowish-brown appearance. DSO is generally caused by _T. rubrum_[11]. It could be developed both in the fingernails and the toenails, although the latter is much more common. Proximal subungal onychomycosis (PSO) constitutes the second class. It is a relatively uncommon subtype, and it occurs when the disease agent invades the proximal nail fold through the cuticle area. The possible consequences of this infection are subungual hyperkeratosis, proximal onycholysis, leukemia and destruction of the proximal nail plate. _T. rubrum_ is the main cause. PSO is very common in AIDS patients, and it could be considered an early clinical marker of the infection [12]. Finally, there is white superficial onychomycosis (WSO). It is the least-common form of onychomycosis, and it occurs when the pathogenic agent invades the superficial layers of the nail plate. It can be recognized by the presence of well-defined so-called white islands on the nail plate surface, which gradually widen as the disease progresses. As a result, the nail becomes soft, rough and friable. The inflammation is minimal, and the main causative agent of this type of infection is _Apergillus niger_. Nail fungal infections are often mistakenly considered to be a minor issue and a purely aesthetic problem that is not worth solving [1,13]. However, onychomycosis has been demonstrated to have a negative impact on a patient's social life, since patients are constantly afraid of passing on the infection to their relatives. They may feel uncomfortable showing their hands and feet, along with the strong impact that the infection may have on individuals at a higher risk of exposure such as immunocompromised patients, with whom the infection sticks more aggressively. Another issue with this pathology is the pharmacological treatment, requiring constant and long-term application, which can make the patient feel discouraged and stop the treatment [14]. Therefore, even if these infections are rarely life-threatening, they can have an important impact on public health and a patient's life [5]. Despite the high frequency of these infections within the population, treatment options remain poor, and given the peculiarity of the affected area, new products are challenging to assess. Treatment is related to the classification and extent of the disease. There are some options to treat fungal nail infections, such as topical antifungals, systemic antifungals and partial or complete removal of the nail plate [15]. Topical treatments include ointments, creams and lacquers, usually containing an antifungal drug. Systemic treatments with antifungal agents are often selected as they are the most effective. However, they may also cause interactions with other medications or gastrointestinal side-effects. Finally, partial nail avulsion drastically reduces the fungal load and may increase the penetration of topical treatments. Complete nail avulsion is necessary for the most persistent and serious cases as a last resort when other treatments have failed [16]. Clearly, onychomycosis is difficult to treat. Achieving complete treatment can take as long as 18 months, and a cure is not achieved at all in 20-25% of treated patients [14]. Furthermore, the disease is associated with very high recurrence rates due to the presence of residual fungal spores or hyphae, with relapses occurring in 6.5-53% of patients [17]. The efficacy of current treatments is limited by the slow growth of toenails, nail keratin thickness preventing the penetration of topical and systemic drugs and the survival of fungi in surrounding environments (such as footwear) for long periods.