Ana Júlio
@ulusofona.pt
PhD Student
Universidade Lusófona/U. Alcalá
I am a PhD Student in Health Sciences at U.Lusófona/U.Alcalá, which researcher area is Ionic Liquids and Controlled Delivery Systems, such as Nanotechnology.
For the scientific point of view, I am interested in Chemical Synthesis, Nanotechnology, Pharmaceutical Technology and Drug Delivery Systems.
EDUCATION
Master Degree in Pharmaceutical Sciences by U.Lusófona
Scopus Publications
Scopus Publications
Khaoula Adouni, Ana Júlio, Celestino Santos-Buelga, Ana M. González-Paramás, Patrícia Filipe, Patricia Rijo, Sofia A. Costa Lima, Salette Reis, Ângela Fernandes, Isabel C.F.R. Ferreira,et al.
Elsevier BV
Abstract The nutritional composition and bioactive properties of roots and rhizomes of Asparagus stipularis were evaluated. Antioxidant activity of extracts obtained by infusion was evaluated using free radicals scavenging and reducing power methods. Porcine liver primary cell was used to check the hepatotoxicity of infusions. Results revealed that Asparagus samples are likely a source of nutrients, such as dietary fibre and essential fatty acids. HPLC-DAD-ESI/MS characterization of infusions allowed the identification and quantitation of 7 phenolic compounds, all hydroxycinnamoyl derivatives, with caffeic acid as the most abundant. Roots infusion contained the highest amounts of these compounds. It also exhibited the highest antioxidant activity in all assays, with EC50 values of 0.44 ± 0.01, 0.98 ± 0.03 and 0.64 ± 0.01 mg/mL for DPPH, ABTS and FRAP assays, respectively, with no toxicity towards PLP2 primary cell cultures (GI50 > 400 μg/mL). PLGA nanoparticles loaded with root extract were prepared using solvent-evaporation double emulsion method. Nanoparticles size was about 260 nm and a polydispersity index around 0.1, with a zeta potential of about -36 mV, as well as a good encapsulation efficiency of approximately 83%. Their morphology was analysed by SEM and spherical polymeric nanoparticles with a smooth surface were observed. FTIR and DSC were also performed, which allowed corroborating the efficacy of the encapsulation and to confirm the production of a stable and robust system to load Asparagus extracts. The developed nanoparticles are expected to be used as delivery systems for bioactive compounds of A. stipularis and they could be used as an innovative dietary supplement.
Ana Júlio, Nádia Remtula, Marisa Nicolai, and Tânia Santos de Almeida
ALIES
Hydroxycinnamic acids, namely caffeic and p-coumaric acids, have several pharmaceutical and cosmetic applications, but due to their low aqueous solubility, their applicability can be limited. Ionic liquids (ILs) have been shown to be a valuable tool to improve the solubility and assist in the incorporation of various phenolic compounds into delivery systems. Thus, this work aims to evaluate the impact of incorporating three choline-based ILs, namely (2-hydroxyethyl)-trimethylammonium-L-phenylalanine [Cho][Phe], (2-hydroxyethyl)-trimethylammonium-L-glutamate [Cho][Glu] and (2-hydroxyethyl)-trimethylammonium-glycinate [Cho][Gly], into an aqueous gel formulation containing the poorly soluble caffeic and p-coumaric acids. The results obtained confirm that the ILs not only increase the drug solubility, but also allow higher amounts of both studied drugs to be incorporated into the gels, without interfering with the stability of the aqueous gels. Moreover, the ILs altered the fluidity of the gels, both in the absence and presence of both phenolic acids, as they increase the viscosity of the formulations, contributing to higher flow resistance of the gel, which may be better accepted by the consumer. Keywords: Ionic liquids; Hydroxycinnamic acids; Poorly soluble drugs; Gels; Increased Viscosity
Ana Júlio, João Guilherme Costa, Catarina Pereira-Leite, and Tânia Santos de Almeida
MDPI AG
Ionic liquids (ILs) have increasingly been studied as key materials to upgrade the performance of many pharmaceutical formulations. In controlled delivery systems, ILs have improved multiple physicochemical properties, showing the relevance of continuing to study their incorporation into these formulations. Transfersomes are biocompatible nanovesicular systems, quite useful in controlled delivery. They have promising characteristics, such as elasticity and deformability, making them suitable for cutaneous delivery. Nonetheless, their overall properties and performance may still be improved. Herein, new TransfersomILs systems to load rutin were developed and the physicochemical properties of the formulations were assessed. These systems were prepared based on an optimized formulation obtained from a Box–Behnken factorial design (BBD). The impact of imidazole-based ILs, cholinium-based ILs, and their combinations on the cell viability of HaCaT cells and on the solubility of rutin was initially assessed. The newly developed TransfersomILs containing rutin presented a smaller size and, in general, a higher association efficiency, loading capacity, and total amount of drug release compared to the formulation without IL. The ILs also promoted the colloidal stability of the vesicles, upgrading storage stability. Thus, ILs were a bridge to develop new TransfersomILs systems with an overall improved performance.
Ana Júlio, Anaisa Sultane, Ana Silveira Viana, Joana Portugal Mota, and Tânia Santos de Almeida
MDPI AG
Lipidic implants are valuable controlled delivery systems that present good biocompatibility and are useful for long-lasting therapies. However, these promising systems can present inflexible drug release profiles that limit their performance. Thus, finding new materials to overcome this drawback is crucial. Herein, lipidic implants containing caffeine and poorly soluble salicylic acid and rutin were developed. The inclusion of Gelucire® 50/02, sucrose, and two biobased ionic liquids, [Cho][Phe] and [Cho][Glu], were evaluated as a mean to improve the performance of the systems. The formulation procedure, dye content distribution, drug content, drug release, water content, and lipidic erosion of the developed systems were assessed. AFM analysis of the implants containing ILs was also performed. The results demonstrated that neither Gelucire® 50/02 nor sucrose were suitable tools to improve the drug release profile. In contrast, the ILs proved to be promising materials for multiple reasons; not only did they facilitate the formulation and incorporation of the studied drugs into the implants, but they also allowed a more suitable release profile, with [Cho][Glu] allowing a higher drug release due to its ability to increase surface wrinkling. Hence, this study showcases ILs as multitalented materials in lipid-based drug implants.
Rita Caparica, Ana Júlio, Filipe Fernandes, Maria Eduarda M. Araújo, João Guilherme Costa, and Tânia Santos de Almeida
MDPI AG
Numerous studies are continuously being carried out in pursuit of formulations with higher performance. Problems such as poor drug solubility, which hinders drug incorporation into delivery systems and bioavailability, or limitations concerning the stability and performance of the formulations may cause difficulties, since solving all these drawbacks at once is a huge challenge. Ionic liquids (ILs), due to their tunable nature, may hypothetically be synthesized for a particular application. Therefore, predicting the impact of a particular combination of ions within an IL in drug delivery could be a useful strategy. Eight ILs, two choline amino acid ILs, two imidazole halogenated ILs, and four imidazole amino acid ILs, were prepared. Their applicability at non-toxic concentrations, for improving solubility and the incorporation of the poorly soluble, ferulic, caffeic, and p-coumaric acids, as well as rutin, into topical emulsions, was assessed. Next, the impact of the ILs on the performance of the formulations was investigated. Our study showed that choosing the appropriate IL leads to a clear upgrade of a topical emulsion, by optimizing multiple features of its performance, such as improving the delivery of poorly soluble drugs, altering the viscosity, which may lead to better sensorial features, and increasing the stability over time.
Ana Júlio, Sofia A. Costa Lima, Salette Reis, Tânia Santos de Almeida, and Pedro Fonte
Elsevier BV
Abstract The low solubility and permeability of drugs are two major challenges in the development of delivery systems, thus the aim of this work was to develop ionic liquid-nanocarrier hybrid systems for delivery of poorly soluble drugs. The ionic liquid-nanocarrier hybrid system loading a poorly soluble drug model, rutin, was obtained by a modified double-emulsion technique. The ionic liquids, (2-hydroxyethyl)-trimethylammonium- l -phenylalaninate [Cho][Phe] or (2-hydroxyethyl)-trimethylammonium- l -glutaminate [Cho][Glu] were used, to obtain the systems, at concentrations where cell viability is maintained. The formulation was optimized to obtain carriers with optimal physicochemical features. The hybrid nanosystems had a diameter less than 500 nm, with good polydispersity index and colloidal stability. The association efficiency of the drug ranged between 35 and 50%, which for a poorly soluble drug is a good achievement, and in formulations with pH 6.7 this parameter increased significantly. A robust ionic liquid-polymer nanoparticle hybrid system was obtained in the presence of polyvinyl alcohol at 2% (w/v), demonstrating their potential to incorporate higher amounts of poorly soluble drugs. The developed hybrid systems may ultimately enhance the therapy of several health problems increasing the quality of life of patients treated with this type of drugs.
Rita Caparica, Ana Júlio, Maria Eduarda Machado Araújo, André Rolim Baby, Pedro Fonte, João Guilherme Costa, and Tânia Santos de Almeida
MDPI AG
The renal cell carcinoma (RCC) is the most common type of kidney cancer. Identifying novel and more effective therapies, while minimizing toxicity, continues to be fundamental in curtailing RCC. Rutin, a bioflavonoid widely found in nature, has shown promising anticancer properties, but with limited applicability due to its poor water solubility and pharmacokinetics. Thus, the potential anticancer effects of rutin toward a human renal cancer cell line (786-O), while considering its safety in Vero kidney cells, was assessed, as well as the applicability of ionic liquids (ILs) to improve drug delivery. Rutin (up to 50 µM) did not show relevant cytotoxic effects in Vero cells. However, in 786-O cells, a significant decrease in cell viability was already observed at 50 µM. Moreover, exposure to rutin caused a significant increase in the sub-G1 population of 786-O cells, reinforcing the possible anticancer activity of this biomolecule. Two choline-amino acid ILs, at non-toxic concentrations, enhanced rutin’s solubility/loading while allowing the maintenance of rutin’s anticancer effects. Globally, our findings suggest that rutin may have a beneficial impact against RCC and that its combination with ILs ensures that this poorly soluble drug is successfully incorporated into ILs–nanoparticles hybrid systems, allowing controlled drug delivery.
Ana Júlio, Rita Caparica, Sofia A. Costa Lima, Ana Sofia Fernandes, Catarina Rosado, Duarte M. F. Prazeres, Salette Reis, Tânia Santos de Almeida, and Pedro Fonte
MDPI AG
The use of functional excipients such as ionic liquids (ILs) and the encapsulation of drugs into nanocarriers are useful strategies to overcome poor drug solubility. The aim of this work was to evaluate the potential of IL-polymer nanoparticle hybrid systems as tools to deliver poorly soluble drugs. These systems were obtained using a methodology previously developed by our group and improved herein to produce IL-polymer nanoparticle hybrid systems. Two different choline-based ILs and poly (lactic-co-glycolic acid) (PLGA) 50:50 or PLGA 75:25 were used to load rutin into the delivery system. The resulting rutin-loaded IL-polymer nanoparticle hybrid systems presented a diameter of 250–300 nm, with a low polydispersity index and a zeta potential of about −40 mV. The drug association efficiency ranged from 51% to 76%, which represents a good achievement considering the poor solubility of rutin. No significant particle aggregation was obtained upon freeze-drying. The presence of the IL in the nanosystem does not affect its sustained release properties, achieving about 85% of rutin released after 72 h. The cytotoxicity studies showed that the delivery system was not toxic to HaCat cells. Our findings may open a new paradigm on the therapy improvement of diseases treated with poorly soluble drugs.
Jocilane Pereira de Oliveira, Alves Barroso Lívia, Ana Júlio, Rita Caparica, Maria Josiane Macedo, Fabiane Neves Silva, Michelle Guimarães Horta, José Fábio Soares, and Tânia Santos de Almeida
ALIES
Tânia Santos de Almeida, Maria Eduarda Machado Araújo, Lucía González Rodríguez, Ana Júlio, Beatriz Garcia Mendes, Rui Miguel Borges dos Santos, and José Artur Martinho Simões
FapUNIFESP (SciELO)
1CBIOS Universidade Lusófona’s Research Center for Biosciences and Health Technologies, Lisboa, Portugal, 2Centro de Química e Bioquímica, Faculdade de Ciências, Universidade de Lisboa, Lisboa, Portugal, 3Centro de Ciências da Saúde, Departamento de Análises Clínicas, Universidade Federal de Santa Catarina, Florianópolis, Brasil, 4CBMR Center for Biomedical Research, Universidade do Algarve, Faro, Portugal
Rita Caparica, Ana Júlio, André Baby, Maria Araújo, Ana Fernandes, João Costa, and Tânia Santos de Almeida
MDPI AG
The development of effective forms to incorporate poorly soluble drugs into delivery systems remains a problem. Thus, it is important to find alternatives such as finding excipients that increase drug solubility. Ionic liquids (ILs), particularly choline-based ILs, have been studied as solubility enhancers in drug delivery systems. Nonetheless, to acknowledge this property as a functionality, it needs to be proven at non-toxic concentrations. Hence, herein two choline-amino acid ILs were studied as functional excipients by evaluating their influence on the solubility of the poorly water-soluble ferulic acid and rutin, while considering their safety. The solubility of the drugs was always higher in the presence of the ILs than in water. Ionic liquids did not affect the radical scavenging activity of the drugs or the cell viability. Moreover, stable oil-in-water (O/W) emulsions were prepared containing each drug and the ILs, allowing a significantly higher drug loading. Globally, our results suggest that choline-based ILs may act as green functional excipients, since at non-toxic concentrations they considerably improve drug solubility/loading, without influencing the antioxidant activity of the drugs, the cell viability, or the stability of the formulations.
Tânia Santos de Almeida, Ana Júlio, Nuno Saraiva, Ana Sofia Fernandes, Maria Eduarda M. Araújo, André Rolim Baby, Catarina Rosado, and Joana Portugal Mota
Informa UK Limited
Abstract Background: Poor drug solubility represents a problem for the development of topical formulations. Since ionic liquids (ILs) can be placed in either lipophilic or hydrophilic solutions, they may be advantageous vehicles in such delivery systems. Nonetheless, it is vital to determine their usefulness when used at concentrations were cell viability is maintained, which was considered herein. Method: Five different ILs were prepared—three imidazole-based ILs: [C2mim][Br], [C4mim][Br], and [C6mim][Br]; and two choline-based ILs: [Cho][Phe] and [Cho][Glu]. Their cytotoxicity in human keratinocytes (HaCat cells), their influence in drug solubility and in percutaneous permeation, using pig skin membranes, was evaluated. Results: Caffeine and salicylic acid were used as model actives. Choline-based ILs proved to be more suitable as functional ingredients, since they showed higher impact on drug solubility and a lower cytotoxicity. The major solubility enhancement was observed for caffeine and further solubility studies were carried out with this active in several concentrations of the choline-based ILs (0.1; 0.2; 0.5; 1.0; 3.0 and 5.0%, w/w) at 25 °C and 32 °C. Solubility was greatly influenced by concentrations up to 0.5%. The choline-based ILs showed no significant impact on the skin permeation, for both actives. The size of the imidazole-based ILs alkyl chain enhances the caffeine solubility and permeation, but also the ILs cytotoxicity. Stable O/W emulsions and gels were prepared containing the less toxic choline-based ILs and caffeine. Conclusions: Our results indicate that the choline-based ILs were effective functional ingredients, since, when used at nontoxic concentrations, they allowed a higher drug loading, while maintaining the stability of the formulations.
Tânia Santos de Almeida, Ana Júlio, Joana Portugal Mota, Patrícia Rijo, and Catarina Pinto Reis
Future Science Ltd
There is a growing need to develop drug-delivery systems that overcome drawbacks such as poor drug solubility/loading/release, systemic side effects and limited stability. Ionic liquids (ILs) offer many advantages and their tailoring represents a valuable tuning tool. Nano-based systems are also prized materials that prevent drug degradation, enhance their transport/distribution and extend their release. Consequently, structures containing ILs and nanoparticles (NPs) have been developed to attain synergistic effects. This overview on the properties of ILs, NPs and of their combined structures, reveals the recent advances in these areas through a review of pertinent literature. The IL-NP structures present enhanced properties and the subsequent performance upgrade proves to be useful in drug delivery, although much is yet to be done.