Application of ionic liquids in the development of sustained delivery systems

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dc.contributor.authorJúlio, Ana
dc.contributor.institutionECTS - School of Health Sciences and Technologies
dc.contributor.supervisorALMEIDA, TÂNIA VANESSA SANTOS DE
dc.contributor.supervisorAberturas Ramos, María del Rosario
dc.date.accessioned2025-12-21T16:10:02Z
dc.date.available2025-12-21T16:10:02Z
dc.date.issued2022
dc.descriptionFunded by ALIES-COFAC for the PADDIC grants 2018 and 2019.
dc.description.abstractThe 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 interfere 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. Consequently, 54 different batches of implants were developed to study the formulation procedure, the dye content distribution, the drug content and drug release, the water content, as well as the lipidic erosion. Gelucire® 50/02 and sucrose were not fitting tools to enhance the drug release profile. On the other hand, 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. iii Finally, new class of nanovesicles containing ILs (TransfersomILs) were developed, having into account an optimized formulation obtained herein from a 15-run, 3-factor, 3-level Box Behnken factorial design (BBD). The TransfersomILs were prepared in the presence of 1-ethyl 3-methylimidazolium bromide [Emim][Br], 2-hydroxyethyl-trimethylammonium glycinate [Cho][Gly], 1-ethyl-3-methylimidazolium glycinate [Emim][Gly] and also using ILs combinations, to incorporate rutin and to assess if ILs could improve the overall performance of the transfersomes. Initially, it was assessed the impact of the ILs and of the ILs combinations on the cell viability of HaCaT cells and on the rutin’s solubility. Then, the physicochemical properties of the new TransfersomILs were evaluated and the results demonstrated that the ILs led to improved systems. Namely, when compared with the tranfersomes without IL, the new TransfersomILs presented a smaller size and, in overall a higher association efficiency, loading capacity, and also a higher total amount of drug release. Additionally, the ILs also contributed to upgrade the storage stability of the nanovesicular systems, by promoting their colloidal stability. Hence, even at low and safe concentrations, ILs can be crucial to facilitate formulation procedures and improve the overall physicochemical properties of controlled drug delivery systems, namely by leading to a higher drug loading and release, by enhancing the stability of systems and even by improving surface characteristics. Thus, this work showcased ILs as key multifunctional materials to upgrade the performance of sustained delivery systems in multiple ways.en
dc.formatapplication/pdf
dc.identifier.urihttp://hdl.handle.net/10437/15703
dc.language.isoeng
dc.rightsopenAccess
dc.subjectDOUTORAMENTO EM CIÊNCIAS DA SAÚDE
dc.subjectCIÊNCIAS DA SAÚDE
dc.subjectLÍQUIDOS IÓNICOS
dc.subjectIMPLANTES LIPÍDICOS
dc.subjectADMINISTRAÇÃO DE MEDICAMENTOS
dc.subjectHEALTH SCIENCES
dc.subjectIONIC LIQUIDS
dc.subjectLIPIDIC IMPLANTS
dc.subjectMEDICATION ADMINISTRATION
dc.titleApplication of ionic liquids in the development of sustained delivery systemsen
dc.titleAplicação de líquidos iónicos no desenvolvimento de sistemas de administração sustentadapt
dc.typedoctoralThesis

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