Ionic liquids with methotrexate moieties as a potential anticancer prodrug: Synthesis, characterization and solubility evaluation

Moshikur, Rahman Md; Chowdhury, Raihan; Wakabayashi, Rie; Tahara, Yoshiro; Moniruzzaman, Muhammad; Goto, Masahiro

doi:10.1016/j.molliq.2019.01.063

Cited by 73 publications

(48 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Physicochemical and Pharmacological Characterization of MTX-Loaded Nanoparticles. Methotrexate (MTX) is a potent anti-inflammatory molecule with a low solubility in physiological fluids 31 and a modest half-life in blood. 32 The formulation of MTX into nanoparticles can overcome the limitations above, thus harnessing the full potential of this drug.…”

Section: ■ Resultsmentioning

confidence: 99%

Modulating Lipoprotein Transcellular Transport and Atherosclerotic Plaque Formation in ApoE^–/– Mice via Nanoformulated Lipid–Methotrexate Conjugates

Francesco

Gurgone

Palomba

et al. 2020

ACS Appl. Mater. Interfaces

View full text Add to dashboard Cite

Macrophage inflammation and maturation into foam cells, following the engulfment of oxidized low-density lipoproteins (oxLDL), are major hallmarks in the onset and progression of atherosclerosis. Yet, chronic treatments with anti-inflammatory agents, such as methotrexate (MTX), failed to modulate disease progression, possibly for the limited drug bioavailability and plaque deposition. Here, MTX–lipid conjugates, based on 1,2-distearoyl- sn -glycero-3-phosphoethanolamine (DSPE), were integrated in the structure of spherical polymeric nanoparticles (MTX-SPNs) or intercalated in the lipid bilayer of liposomes (MTX-LIP). Although, both nanoparticles were colloidally stable with an average diameter of ∼200 nm, MTX-LIP exhibited a higher encapsulation efficiency (>70%) and slower release rate (∼50% at 10 h) compared to MTX-SPN. In primary bone marrow derived macrophages (BMDMs), MTX-LIP modulated the transcellular transport of oxLDL more efficiently than free MTX mostly by inducing a 2-fold overexpression of ABCA1 (regulating oxLDL efflux), while the effect on CD36 and SRA-1 (regulating oxLDL influx) was minimal. Furthermore, in BMDMs, MTX-LIP showed a stronger anti-inflammatory activity than free MTX, reducing the expression of IL-1β by 3-fold, IL-6 by 2-fold, and also moderately of TNF-α. In 28 days high-fat-diet-fed apoE –/– mice, MTX-LIP reduced the mean plaque area by 2-fold and the hematic amounts of RANTES by half as compared to free MTX. These results would suggest that the nanoenhanced delivery to vascular plaques of the anti-inflammatory DSPE-MTX conjugate could effectively modulate the disease progression by halting monocytes’ maturation and recruitment already at the onset of atherosclerosis.

show abstract

Section: ■ Resultsmentioning

confidence: 99%

Modulating Lipoprotein Transcellular Transport and Atherosclerotic Plaque Formation in ApoE^–/– Mice via Nanoformulated Lipid–Methotrexate Conjugates

Francesco

Gurgone

Palomba

et al. 2020

ACS Appl. Mater. Interfaces

View full text Add to dashboard Cite

show abstract

“…An API-IL of methotrexate, a chemotherapeutic, was prepared with a choline counter-ion, showing a 5000fold increase in aqueous solubility and lower IC 50 values against a cancer cell line, as depicted in Figure 3. [55] Silva et al [56] synthesized a diclofenac-imidazolium ionic liquid, which has a melting point around 92 °C, but showed 100 times improvement in drug solubility in water. They found that the IL formation was driven largely by transfer of the hydrogen atom from the carboxylic acid to the imidazolium ring nitrogen.…”

Section: Active Pharmaceutical Ingredient-ionic Liquid (Api-il)mentioning

confidence: 99%

“…b) In vitro antitumor activity, as measured by HeLa cell viability, shows MTX-ILs have significantly lower IC50 values than the standard treatment of [Na][MTX]. Reproduced with permission [55]. Copyright 2019, Elsevier.…”

mentioning

confidence: 99%

Recent Advances in Ionic Liquids in Biomedicine

2021

View full text Add to dashboard Cite

The use of ionic liquids and deep eutectic solvents in biomedical applications has grown dramatically in recent years due to their unique properties and their inherent tunability. This review will introduce ionic liquids and deep eutectics and discuss their biomedical applications, namely solubilization of drugs, creation of active pharmaceutical ingredients, delivery of pharmaceuticals through biological barriers, stabilization of proteins and other nucleic acids, antibacterial agents, and development of new biosensors. Current challenges and future outlooks are discussed, including biocompatibility, the potential impact of the presence of impurities, and the importance of understanding the microscopic interactions in ionic liquids in order to design task-specific solvents.

show abstract

“…MTX is used in cervical, colorectal, lung and breast cancers as well as leukemia and osteosarcoma [26,27]. BTZ, SRF and MTX are similarly having low water solubility with 53.2 μg/ml, 1.7 μg/ml, and 0.1 mg/ml, respectively [28][29][30].…”

Section: Introductionmentioning

confidence: 99%

Carrier-free nanodrugs for safe and effective cancer treatment

Karaosmanoglu

Zhou

Shi

et al. 2021

Journal of Controlled Release

View full text Add to dashboard Cite

Clinical applications of many anti-cancer drugs are restricted due to their hydrophobic nature, requiring use of harmful organic solvents for administration, and poor selectivity and pharmacokinetics resulting in off-target toxicity and inefficient therapies. A wide variety of carrier-based nanoparticles have been developed to tackle these issues, but such strategies often fail to encapsulate drug efficiently and require significant amounts of inorganic and/or organic nanocarriers which may cause toxicity problems in the long term. Preparation of nanoformulations for the delivery of water insoluble drugs without using carriers is thus desired, 2 requiring elegantly designed strategies for products with high quality, stability and performance. These strategies include simple self-assembly or involving chemical modifications via coupling drugs together or conjugating them with various functional molecules such as lipids, carbohydrates and photosensitizers. During nanodrugs synthesis, insertion of redox-responsive linkers and tumor targeting ligands endows them with additional characteristics like on-target delivery, and conjugation with immunotherapeutic reagents enhances immune response alongside therapeutic efficacy. This review aims to summarize the methods of making carrier-free nanodrugs from hydrophobic drug molecules, evaluating their performance, and discussing the advantages, challenges, and future development of these strategies.

show abstract

Ionic liquids with methotrexate moieties as a potential anticancer prodrug: Synthesis, characterization and solubility evaluation

Cited by 73 publications

References 32 publications

Modulating Lipoprotein Transcellular Transport and Atherosclerotic Plaque Formation in ApoE^–/– Mice via Nanoformulated Lipid–Methotrexate Conjugates

Modulating Lipoprotein Transcellular Transport and Atherosclerotic Plaque Formation in ApoE^–/– Mice via Nanoformulated Lipid–Methotrexate Conjugates

Recent Advances in Ionic Liquids in Biomedicine

Carrier-free nanodrugs for safe and effective cancer treatment

Contact Info

Product

Resources

About

Ionic liquids with methotrexate moieties as a potential anticancer prodrug: Synthesis, characterization and solubility evaluation

Cited by 73 publications

References 32 publications

Modulating Lipoprotein Transcellular Transport and Atherosclerotic Plaque Formation in ApoE–/– Mice via Nanoformulated Lipid–Methotrexate Conjugates

Modulating Lipoprotein Transcellular Transport and Atherosclerotic Plaque Formation in ApoE–/– Mice via Nanoformulated Lipid–Methotrexate Conjugates

Recent Advances in Ionic Liquids in Biomedicine

Carrier-free nanodrugs for safe and effective cancer treatment

Contact Info

Product

Resources

About

Modulating Lipoprotein Transcellular Transport and Atherosclerotic Plaque Formation in ApoE^–/– Mice via Nanoformulated Lipid–Methotrexate Conjugates

Modulating Lipoprotein Transcellular Transport and Atherosclerotic Plaque Formation in ApoE^–/– Mice via Nanoformulated Lipid–Methotrexate Conjugates