Aplicación de líquidos iónicos en el desarrollo de sistemas de administración sostenida
- Autores: Ana Luísa Gomes Júlio
- Directores de la Tesis: Tânia Almeida de Almeida (dir. tes.), María del Rosario Aberturas Ramos (codir. tes.)
- Lectura: En la Universidad de Alcalá ( España ) en 2023
- Idioma: español
- Tribunal Calificador de la Tesis: Cláudia Daniela Nunes (presid.), Fidel Ortega Ortiz-Apodaca (secret.), Ana Rita Jesus (voc.)
- Programa de doctorado: Programa de Doctorado en Ciencias de la Salud por la Universidad de Alcalá
- Materias:
- Enlaces
- Tesis en acceso abierto en: TESEO
- Resumen
The development of drug delivery systems, namely for controlled release, present some problems such as the poor solubility and bioavailability of many drugs, the inflexible drug release profiles, the possible side effects, and the low drug selectivity for target tissues. So, finding new strategies and/or excipients to surpass these challenges is crucial and ionic liquids (ILs) may be key materials in this matter. Hence, the aim of this thesis was to explore the applicability of ILs in the development of more effective sustained drug delivery systems, namely polymeric nanoparticles, lipidic implants, and transfersomes, all containing ILs.
Firstly, IL-polymer nanoparticle hybrid systems containing rutin were prepared using the polymer poly(lactic-co-glycolic acid) (PLGA) and two biobased ILs, (2-hydroxyethyl)-trimethylammonium-L-phenylalaninate [Cho][Phe] and the (2-hydroxyethyl)-trimethylammonium-L-glutaminate [Cho][Glu]. Two different ratios of PLGA (50:50 and 75:25), were studied and the hybrid systems showed a particle size between 250 nm and 300 nm, a low polydispersity index, a zeta potential around - 40 mV and a drug association efficiency (AE) ranging from 51% to 76%. Since rutin is a poorly soluble drug, the obtained AE was quite relevant showing that the ILs were crucial to load rutin into the nanosystem. Additionally, the ILs did not interfered with the sustained release properties of the nanosystem and allowed a rutin release of about 85% after 72 h. Also, upon freeze-drying no particle aggregation was observed, showing the stability of the systems containing ILs. Finally, the results also indicated that the developed systems may be suitable for skin topical applications since no relevant skin permeability was observed and no toxicity was shown in the cell viability study in HaCaT, human keratinocytes.
Lipidic implants containing caffeine, salicylic acid, or rutin, were also prepared. Different compositions were studied, namely the incorporation of the ILs [Cho][Phe] and [Cho][Glu], and of two different release adjuvants, Gelucire® 50/02 and sucrose. The formulation procedure, the dye content distribution, the drug content and drug release, the water content, as well as the lipidic erosion were all studied. Neither Gelucire® 50/02 nor sucrose were suitable tools to enhance the drug release profile. In contrast, results showed that ILs were valuable materials by facilitating the formulation procedure, improving drug loading and by allowing a more suitable release profile. Moreover, atomic force microscopy (AFM) analysis displayed that the presence of ILs conveyed a more wrinkled surface to the implants, with the [Cho][Glu] leading to a more noticeable surface wrinkling, consistent with the higher drug release observed in the presence of this IL.
