Hybrid nanosystems for cancer therapy

• Autor(a) principal: Teixeira, Cláudia Patrícia Vilela
• Data de Publicação: 2022
• Tipo de documento: Dissertação
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/10348/11817
• topic: Cancer; Nanotechnology

Cancer is a group of diseases that can affect multiple organs or tissues in the human body. Due to the rapid division and spread of abnormal cells, it is one of the leading causes of death worldwide. Therefore, there is an urgent need to develop effective therapies to circumvent the drawbacks of conventional therapies, such as multidrug resistance (MDR), limited water solubility, and lack of selectivity of chemotherapeutic agents, all of which affect their distribution, efficacy, and safety. Nanotechnology represents a promising opportunity for the development of new strategies for cancer diagnosis and treatment, as it can provide pharmacokinetic and pharmacodynamic advantages. The use of nanosystems is also advantageous over conventional cancer therapies because they can act both actively and passively on cancer tissues, have higher efficacy and lower toxicity. Cubosomes have gained increasing interest in research because they have several advantages as drug delivery systems, such as the ability to encapsulate multiple drugs, a high payload due to their large internal surface area, which also promotes the controlled release of bioactive agents. The main objective of this work was to develop and optimize a hybrid nanosystem formulation containing doxorubicin (DOX), a first-line chemotherapeutic agent. The cubosomes were developed using various methods including hydrotrope, lipid film hydration, emulsification, and ion-paired DODAB-drug. After their development, the formulations with and without drug were characterized in terms of size, surface charge, encapsulation efficiency and drug content, physicochemical properties, and stability, which allowed the selection of the most promising formulations. Finally, therapeutic performance studies were performed to investigate the kinetic release profiles as well as the in vitro cytotoxicity of the selected cubosomes in different cancer cell lines. The characterization of the developed formulations revealed that cubosomes have an acceptable zeta potential (≈ -20 mV), an adequate size (< 250 nm), a polydispersity index acceptable for therapeutic use (≈ 0.25), a high encapsulation efficiency (> 84%), and interesting biophysical properties with cubic phases that encompass lipid and aqueous domains. Therapeutic performance studies also showed relevant therapeutic properties. For example, kinetic release profiles showed accelerated release of DOX in a simulated tumour environment and minimal release under normal physiological conditions, indicating the potential of these formulations to minimise cytotoxicity in healthy cells. In conclusion the formulations developed have potential to be explored in cancer therapy.