Methotrexate-based ionic liquid as a potent anticancer drug for oral delivery: In vivo pharmacokinetics, biodistribution, and antitumor efficacy

Moshikur, Rahman Md; Ali, Korban; Wakabayashi, Rie; Moniruzzaman, Muhammad; Goto, Masahiro

doi:10.1016/j.ijpharm.2021.121129

Cited by 24 publications

(13 citation statements)

References 33 publications

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“…100 μL) were collected at 1, 3, 6, 9, and 12 h after administration. Similarly, a single dose (100 mg/kg) of Lev salt was orally administrated using a gavage needle . Blood (ca.…”

Section: Methodsmentioning

confidence: 99%

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Transformation of Hydrophilic Drug into Oil-Miscible Ionic Liquids for Transdermal Drug Delivery

Moshikur

Shimul

Uddin

et al. 2022

ACS Appl. Mater. Interfaces

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The transdermal delivery of hydrophilic drugs remains challenging owing to their poor ability to permeate the skin; formulation with oil media is difficult without adding chemical permeation enhancers or co-solvents. Herein, we synthesized 12 oil-miscible ionic liquid (IL) drugs comprising lidocaine-, imipramine-, and levamisole (Lev)-hydrochloride with fatty acid permeation enhancers, i.e., laurate, oleate, linoleate, and stearate as counterions. A set of in vitro and in vivo studies was performed to investigate the potency and deliverability of the transdermal drug formulations. All of the synthesized compounds were freely miscible with pharmaceutically acceptable solvents/agents (i.e., ethanol, N-methyl pyrrolidone, Tween 20, and isopropyl myristate (IPM)). In vitro permeation studies revealed that the oleate-based Lev formulation had 2.6-fold higher skin permeation capability than the Lev salts and also superior ability compared with the laurate-, linoleate-, and stearate-containing samples. Upon in vivo transdermal administration to mice, the peak plasma concentration, elimination half-life, and area under the plasma concentration curve values of Lev-IL were 4.6-, 2.9-, and 5.4-fold higher, respectively, than those of the Lev salt. Furthermore, in vitro skin irritation and in vivo histological studies have demonstrated that Lev-IL has excellent biocompatibility compared with a conventional ionic liquid-based carrier. The results indicate that oil-miscible IL-based drugs provide a simple and scalable strategy for the design of effective transdermal drug delivery systems.

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“…100 μL) were collected at 1, 3, 6, 9, and 12 h after administration. Similarly, a single dose (100 mg/kg) of Lev salt was orally administrated using a gavage needle . Blood (ca.…”

Section: Methodsmentioning

confidence: 99%

“…Similarly, a single dose (100 mg/kg) of Lev salt was orally administrated using a gavage needle. 28 Blood (ca. 100 μL) was collected at 0.5, 1, 2, 3, 6, 9, and 12 h after administration.…”

Section: ■ Materials and Methodsmentioning

confidence: 99%

Transformation of Hydrophilic Drug into Oil-Miscible Ionic Liquids for Transdermal Drug Delivery

Moshikur

Shimul

Uddin

et al. 2022

ACS Appl. Mater. Interfaces

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“…[12,70] After being administered to mice, the API-ILs demonstrated higher oral bioavailability than the free drugs (Figure 6B). For example, the IL of proline ethyl ester with methotrexate had 4.6-fold higher oral bioavailability and lower systemic toxicity than sodium [61,70] methotrexate. The methotrexate-IL suppressed tumor growth more than free methotrexate, indicating the advantages of ILbased oral delivery systems.…”

Section: Oral Drug Deliverymentioning

confidence: 99%

“…The methotrexate-IL suppressed tumor growth more than free methotrexate, indicating the advantages of ILbased oral delivery systems. [70] In another study, we converted crystalline favipiravir into an ionic liquid to address the poor bioavailability and formulation challenges. [12] After oral dosing in mice, the synthesized favipiravir-ILs showed improved oral bioavailability and drug accumulation in major organs compared with the control favipiravir formulation.…”

Section: Oral Drug Deliverymentioning

confidence: 99%

Pharmaceutical Applications of Ionic Liquids: A Personal Account

Moshikur

Goto

2023

The Chemical Record

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Ionic liquids (ILs) have been extensively used in drug formulation and delivery as designer solvents and other components because of their inherent tunability and useful physicochemical and biopharmaceutical properties. ILs can be used to manage some of the operational and functional challenges of drug delivery, including drug solubility, permeability, formulation instability, and in vivo systemic toxicity, that are associated with conventional organic solvents/agents. Furthermore, ILs have been recognized as potential solvents to address the polymorphism, limited solubility, poor permeability, instability, and low bioavailability of crystalline drugs. In this account, we discuss the technological progress and strategies toward designing biocompatible ILs and explore potential biomedical applications, namely the solubilization of small and macromolecular drugs, the creation of active pharmaceutical ingredients, and the delivery of pharmaceuticals.

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“…12 ILs have been used widely in various domains, including enzyme catalysis, 13 electrochemistry, 14,15 gas storage and separation, 16,17 self-assembly, and in various biomedical applications throughout the past decade. [18][19][20] ILs have melting point values under 100 1C and comprise both organic cations and inorganic anions. 21 Because their cation and anion can be adjusted to alter their physicochemical characteristics, such as their viscosity, hydrophobicity, density, and solubility, they have earned the term ''designer solvents''.…”

Section: Introductionmentioning

confidence: 99%

Effect of mixtures of ionic liquids and water on the structure and stability of the insulin dimer: a combined DFT and MD simulation study

Lakshman,

Rubavathy,

Priyankha

et al. 2023

New J. Chem.

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Methotrexate-based ionic liquid as a potent anticancer drug for oral delivery: In vivo pharmacokinetics, biodistribution, and antitumor efficacy

Cited by 24 publications

References 33 publications

Transformation of Hydrophilic Drug into Oil-Miscible Ionic Liquids for Transdermal Drug Delivery

Transformation of Hydrophilic Drug into Oil-Miscible Ionic Liquids for Transdermal Drug Delivery

Pharmaceutical Applications of Ionic Liquids: A Personal Account

Effect of mixtures of ionic liquids and water on the structure and stability of the insulin dimer: a combined DFT and MD simulation study

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