Tesis Doctorales de la Universidad de Alcalá
Autor/aVasques Roque, Luis Miguel
DepartamentoBiología de Sistemas
Director/aMolpeceres García del Pozo, Jesús
Directores/asBeco Pinto Reis, Ana Catarina; Dias de Mendonça Rijo, Patricia
Fecha de defensa04/03/2019
CalificaciónSobresaliente Cum Laude
ProgramaCiencias de la Salud (RD 99/2011)
Mención internacionalSi
ResumenOral candidiasis is an opportunistic fungal infection that generally affects people with immunodeficiency due to viral infection or acquired immunodeficiency associated to other causes but in some rare cases, it can also affect healthy people. Despite the advances in the treatment of the oral candidiasis, polyens (like nystatin) and azoles are still the most used antifungal agents. In addition, most of those treatments present some disadvantages such as poor oral absorption of the drug, alcohol content in dosage form and they generally require a very high frequency of administrations. Therefore, the major challenge in the treatment may be focused on the improvement of the oral absorption of the antifungal agents through oral or buccal mucosa using bioadhesive dosage forms. This thesis aimed to develop a suitable buccal mucoadhesive nanoparticle (NP) formulation containing antifungal agents for the local treatment of oral candidiasis. Several types of polymeric particles with an encapsulated antifungal agent were prepared and further included into a toothpaste, an oral gel and oral films (all free of alcohol). Nystatin (Nys) was herein chosen as the reference drug because it is one of the main antifungal drug used. In this context, three different systems of nanoparticles (NPs), Polylactic acid, Poly(lactic-co-glycolic) acid and Alginate, were selected since they present a small particle size (300 to 800 nm), homogenous size distribution, appropriate surface charge, high encapsulation efficiency of Nys (above 70%), prolonged release profile, high adhesion capacity to oral mucosa, permeation capacity through the oral mucosa and safety profile. Also, the NPs successfully maintained the activity of Nys over time. Concerning the stability study the formulations were stable for 6 months. In addition, instead of Nys, extracts from Glycyrrhiza glabra (Licorice) were prepared and their antifungal activity was studied. The results obtained showed that ethanolic extract of Glycyrrhiza glabra L. was the most active extract and that the loaded NPs were successfully produced, presenting a mean size between 100-900 nm and a negative surface charge with high encapsulation efficiency of the extract. All the results obtained during this PhD program demonstrated that the nanoparticles can efficiently improve the treatment of oral candidiasis, increasing the stability of the antifungal agents (as compound or extract) and they can improve the treatment in the public health by increasing the patient¿s compliance.