Hidrogel à base hidroxietilcelulose (HEC) com lipossomas contendo 5-fluorouracil: caracterização de estabilidade, propriedades reológicas, textura e bioadesão

Abstract

Non-melanoma skin cancer occupies the 4th position in the world in terms of incidence among other types of cancer, with squamous cell carcinoma being the most common subtype. 5-FU is a drug widely used in the treatment of skin cancer and acts as a pyrimidine analogue, indirectly interfering with cell growth. However, its physicochemical characteristics limit its passage through the main barrier of the skin, the stratum corneum, demanding the need to optimize its delivery through its encapsulation in nanosystems, such as liposomes. These nanometric vesicles proved to be promising alternatives in the delivery of hydrophilic drugs, such as 5-FU, since they promote numerous advantages, among them the optimization of penetration and diffusion of 5-FU through the layers of the skin, which can be enhanced when associated liposomes to chemical skin penetration promoters, such as Span 20. Hydrogels based on biocompatible and biodegradable polymers, such as hydroxyethylcellulose (HEC), can be associated with liposomal dispersions to enable their retention at the site of action, providing ideal mechanical properties for the therapeutic proposal of a semi-solid formulation, to be applied topically in those affected by skin cancer. Thus, the study aimed to develop and characterize hydrogels with liposomes containing 5-FU, in addition to evaluating their preliminary stability and investigating their rheological behavior, texture profile and bioadhesion. Thus, the physical-chemical characterization of liposomes showed values of 88.08 nm, 0.169, -12.3mV, for particle size, PDI and zeta potential, respectively, in addition to encapsulation efficiency around 50.20%. After producing the 2% HEC hydrogel, the developed nanocarriers were incorporated and the obtained formulations had their preliminary stability confirmed, even after being subjected to different conditions for a period of 30 days, based on parameters such as spreadability, viscosity, pH and density. Furthermore, the addition of liposomes did not compromise the rheological characteristics, with pseudoplastic and thixotropic behavior normally observed in hydrogels. Thus, the systems proposed here were successfully developed, demonstrating that they are potential therapeutic alternatives for the topical delivery of 5-FU, since they presented favorable mechanical characteristics for application, such as viscosity and spreadability, which hinder flow and increase retention and bioavailability of the 5-FU. drug at the site of action, which may contribute to the reduction of therapeutic doses and greater patient acceptability.