Ionic Liquid-Polymer Nanoparticle Hybrid Systems as New Tools to Deliver Poorly Soluble Drugs

Júlio, Ana; Caparica, Rita; Lima, Sérgio; Fernandes, Ana Sofia; Rosado, Catarina; Prazeres, D.M.F.; Reis, Salette; Almeida, Tânia Santos de; Fonte, Pedro

doi:10.3390/nano9081148

Cited by 43 publications

(40 citation statements)

References 76 publications

(164 reference statements)

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“…Finally, it was also assessed the release of the rutin from the freshly prepared IL-nanoparticle hybrid systems. An initial burst was observed, as expected, probably due to the rutin adsorbed in the surface of the nanoparticles [35,45]. Nonetheless, this burst release of about 45% happened only after 5 h, probably due to a higher affinity of rutin to the IL-nanoparticles hybrid system, followed by sustained release up to 72 h. This release profile is important to enhance the therapeutic effect and reduce the number of administrations required.…”

Section: Discussionsupporting

confidence: 64%

“…Rutin was loaded in each hybrid system at the maximum solubility of this drug in the presence of either IL, namely, 2.49 mg/mL (4100 µM) with 0. Additionally, the [Cho][Phe]-nanoparticle hybrid system demonstrated that an enhancement of 0.1% of the incorporated IL did not interfere with the hybrid nanosystems stability, but allowed a higher incorporation of the drug and a 10% increase in the AE when compared with the previous prepared hybrid IL-nanocarrier [35]. This shows that the amount of IL impacts drug loading and AE.…”

Section: Discussionmentioning

confidence: 85%

“…Nonetheless, the low aqueous solubility of rutin represents an impairment for this incorporation in drug delivery systems. In fact, in a previous study, we have shown that nanoparticles combined with 0.2% of [Cho][Phe] allowed us to incorporate rutin with an AE of 75.6%, which in the absence of the IL was not possible [35,37]. Hence, in this study, we prepared IL-nanoparticles hybrid systems, loaded and unloaded with rutin, using the concentrations of [Cho][Phe] and [Cho][Gly], where cell viability was maintained in Vero cells line.…”

Section: Discussionmentioning

confidence: 99%

“…To evaluate the cytotoxicity of rutin and of the ILs, individually and in combination, cell viability was determined using the MTT reduction assay. Vero and 786-O cells were seeded at a density of 5 × 10 3 and 3 × 10 3 per well, respectively, in 200 µL culture medium in 96-well plates and incubated for 24 h. Cells were then incubated, either with rutin (0-250 µM), with [Cho][Phe] (0-0.5%, v/v) or with [Cho][Gly] (0-0.5%, v/v) individually, or, with rutin (0-250 µM) in combination with [Cho][Phe] (0.3%, v/v) or with [Cho][Gly] (0.2%, v/v) for 48 h. The MTT reduction assay was then carried out according to previously published procedures [24,35]. Absorbance values for untreated control cells correspond to 100% of cell viability.…”

Section: Mtt Assaymentioning

confidence: 99%

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Anticancer Activity of Rutin and Its Combination with Ionic Liquids on Renal Cells

et al. 2020

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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.

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Section: Discussionsupporting

confidence: 64%

Section: Discussionmentioning

confidence: 85%

Section: Discussionmentioning

confidence: 99%

Section: Mtt Assaymentioning

confidence: 99%

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Anticancer Activity of Rutin and Its Combination with Ionic Liquids on Renal Cells

et al. 2020

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“…The authors suggested that the choline-based ILs could be used as functional ingredients in drug delivery systems suitable for enhancing solubility of other hydrophilic drugs. The use of ILs as functional excipients to overcome poor drug solubility has been proposed recently by Júlio et al [ 217 ]. The authors proposed efficient, non-toxic IL-polymer nanoparticle hybrid systems composed of choline-based ILs and poly (lactic-co-glycolic acid) [PLGA] 50:50 or 75:25 to load rutin into the delivery system.…”

Section: Usefulness Of Ionic Liquids In Medicinementioning

confidence: 99%

Ionic Liquids Toxicity—Benefits and Threats

Flieger

2020

IJMS

246

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Ionic liquids (ILs) are solvents with salt structures. Typically, they contain organic cations (ammonium, imidazolium, pyridinium, piperidinium or pyrrolidinium), and halogen, fluorinated or organic anions. While ILs are considered to be environmentally-friendly compounds, only a few reasons support this claim. This is because of high thermal stability, and negligible pressure at room temperature which makes them non-volatile, therefore preventing the release of ILs into the atmosphere. The expansion of the range of applications of ILs in many chemical industry fields has led to a growing threat of contamination of the aquatic and terrestrial environments by these compounds. As the possibility of the release of ILs into the environment s grow systematically, there is an increasing and urgent obligation to determine their toxic and antimicrobial influence on the environment. Many bioassays were carried out to evaluate the (eco)toxicity and biodegradability of ILs. Most of them have questioned their “green” features as ILs turned out to be toxic towards organisms from varied trophic levels. Therefore, there is a need for a new biodegradable, less toxic “greener” ILs. This review presents the potential risks to the environment linked to the application of ILs. These are the following: cytotoxicity evaluated by the use of human cells, toxicity manifesting in aqueous and terrestrial environments. The studies proving the relation between structures versus toxicity for ILs with special emphasis on directions suitable for designing safer ILs synthesized from renewable sources are also presented. The representants of a new generation of easily biodegradable ILs derivatives of amino acids, sugars, choline, and bicyclic monoterpene moiety are collected. Some benefits of using ILs in medicine, agriculture, and the bio-processing industry are also presented.

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Percutaneous Delivery of Oncogel for Targeted Liver Tumor Ablation and Controlled Release of Therapeutics

Albadawi,

Zhang,

Keum

et al. 2024

Advanced Materials

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Advanced‐stage liver cancers are associated with poor prognosis and have limited treatment options, often leading the patient to hospice care. Percutaneous intratumoral injection of anticancer agents has emerged as a potential alternative to systemic therapy to overcome tumor barriers, increase bioavailability, potentiate immunotherapy, and avoid systemic toxicity, which advanced‐stage cancer patients cannot tolerate. Here, an injectable OncoGel (OG) comprising of a nanocomposite hydrogel loaded with an ionic liquid (IL) is developed for achieving a predictable and uniform tumor ablation and long‐term slow release of anticancer agents into the ablation zone. Rigorous mechanical, physiochemical, drug release, cytotoxicity experiments, and ex vivo human tissue testing identify an injectable version of the OG with bactericidal properties against highly resistant bacteria. Intratumoral injection of OG loaded with Nivolumab (Nivo) and doxorubicin (Dox) into highly malignant tumor models in mice, rats, and rabbits demonstrates enhanced survival and tumor regression associated with robust tissue ablation and drug distribution throughout the tumor. Mass cytometry and proteomic studies in a mouse model of colorectal cancer that often metastasizes to the liver indicate an enhanced anticancer immune response following the intratumoral injection of OG. OG may augment immunotherapy and potentially improve outcomes in liver cancer patients.

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Ionic Liquid-Polymer Nanoparticle Hybrid Systems as New Tools to Deliver Poorly Soluble Drugs

Cited by 43 publications

References 76 publications

Anticancer Activity of Rutin and Its Combination with Ionic Liquids on Renal Cells

Anticancer Activity of Rutin and Its Combination with Ionic Liquids on Renal Cells

Ionic Liquids Toxicity—Benefits and Threats

Percutaneous Delivery of Oncogel for Targeted Liver Tumor Ablation and Controlled Release of Therapeutics

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