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Ionic Liquids in Drug Development, Formulation, and Delivery

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pharmacology".

Deadline for manuscript submissions: closed (28 February 2021) | Viewed by 17709

Special Issue Editors


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Guest Editor

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Guest Editor
Ciências Químicas e Biomoléculas, Escola Superior de Saúde – Instituto Politécnico do Porto, Rua Dr. António Bernardino de Almeida, 400, 4200 - 072 Porto, Portugal
Interests: ionic liquids; development of new drugs; structural analysis of organic molecules; antibiotic resistance; therapeutic applications of ionic liquids; peptide synthesis
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Special Issue Information

Dear Colleagues,

The International Journal of Molecular Sciences is currently running a Special Issue entitled “Ionic Liquids In Drug Development, Formulation, And Delivery”. This Special Issue will address cutting-edge scientific research and technological applications focused on ionic liquids. Contributions on the emerging roles for ionic liquids in pharmaceutical sciences, from drug development and drug formulation to drug delivery, will be most welcome. We thus invite authors who are leading experts in this field to contribute review or original articles to promote, integrate, and disseminate the latest developments in this particular and growing area of research and innovation.

Potential topics include but are not limited to the following:

  • Ionic liquids in pharmaceutical applications;
  • Ionic liquids in drug development;
  • Ionic liquids in drug formulation;
  • Ionic liquids in drug delivery;
  • Biological properties of ionic liquids;
  • Ionic liquids as active pharmaceutical ingredients.

Prof. Dr. Paula A. C. Gomes
Prof. Dr. Ricardo F Ferraz
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • ionic liquids
  • deep eutectic solvents
  • drug delivery
  • drug-derived ionic liquids
  • drug development
  • drug formulation

Published Papers (4 papers)

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Research

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20 pages, 1715 KiB  
Article
The Impact of [C16Pyr][Amp] on the Aggressiveness in Breast and Prostate Cancer Cell Lines
by Filipa Quintela Vieira, Ângela Marques-Magalhães, Vera Miranda-Gonçalves, Ricardo Ferraz, Mónica Vieira, Cristina Prudêncio, Carmen Jerónimo and Regina Augusta Silva
Int. J. Mol. Sci. 2020, 21(24), 9584; https://doi.org/10.3390/ijms21249584 - 16 Dec 2020
Cited by 4 | Viewed by 2140
Abstract
Breast (BrCa) and prostate (PCa) cancers are the most common malignancies in women and men, respectively. The available therapeutic options for these tumors are still not curative and have severe side effects. Therefore, there is an urgent need for more effective antineoplastic agents. [...] Read more.
Breast (BrCa) and prostate (PCa) cancers are the most common malignancies in women and men, respectively. The available therapeutic options for these tumors are still not curative and have severe side effects. Therefore, there is an urgent need for more effective antineoplastic agents. Herein, BrCa, PCa, and benign cell lines were treated with two ionic liquids and two quinoxalines and functional experiments were performed—namely cell viability, apoptosis, cytotoxicity, and colony formation assays. At the molecular level, an array of gene expressions encompassing several molecular pathways were used to explore the impact of treatment on gene expression. Although both quinoxalines and the ionic liquid [C2OHMIM][Amp] did not show any effect on the BrCa and PCa cell lines, [C16Pyr][Amp] significantly decreased cell viability and colony formation ability, while it increased the apoptosis levels of all cell lines. Importantly, [C16Pyr][Amp] was found to be more selective for cancer cells and less toxic than cisplatin. At the molecular level, this ionic liquid was also associated with reduced expression levels of CPT2, LDHA, MCM2, and SKP2, in both BrCa and PCa cell lines. Hence, [C16Pyr][Amp] was shown to be a promising anticancer therapeutic agent for BrCa and PCa cell lines. Full article
(This article belongs to the Special Issue Ionic Liquids in Drug Development, Formulation, and Delivery)
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9 pages, 707 KiB  
Communication
Building on Surface-Active Ionic Liquids for the Rescuing of the Antimalarial Drug Chloroquine
by Ana Teresa Silva, Lis Lobo, Isabel S. Oliveira, Joana Gomes, Cátia Teixeira, Fátima Nogueira, Eduardo F. Marques, Ricardo Ferraz and Paula Gomes
Int. J. Mol. Sci. 2020, 21(15), 5334; https://doi.org/10.3390/ijms21155334 - 27 Jul 2020
Cited by 17 | Viewed by 3002
Abstract
Ionic liquids derived from classical antimalarials are emerging as a new approach towards the cost-effective rescuing of those drugs. Herein, we disclose novel surface-active ionic liquids derived from chloroquine and natural fatty acids whose antimalarial activity in vitro was found to be superior [...] Read more.
Ionic liquids derived from classical antimalarials are emerging as a new approach towards the cost-effective rescuing of those drugs. Herein, we disclose novel surface-active ionic liquids derived from chloroquine and natural fatty acids whose antimalarial activity in vitro was found to be superior to that of the parent drug. The most potent ionic liquid was the laurate salt of chloroquine, which presented IC50 values of 4 and 110 nM against a chloroquine-sensitive and a chloroquine-resistant strain of Plasmodium falciparum, respectively, corresponding to an 11- and 6-fold increase in potency as compared to the reference chloroquine bisphosphate salt against the same strains. This unprecedented report opens new perspectives in both the fields of malaria chemotherapy and of surface-active ionic liquids derived from active pharmaceutical ingredients. Full article
(This article belongs to the Special Issue Ionic Liquids in Drug Development, Formulation, and Delivery)
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Review

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50 pages, 9597 KiB  
Review
The Role of Ionic Liquids in the Pharmaceutical Field: An Overview of Relevant Applications
by Sónia N. Pedro, Carmen S. R. Freire, Armando J. D. Silvestre and Mara G. Freire
Int. J. Mol. Sci. 2020, 21(21), 8298; https://doi.org/10.3390/ijms21218298 - 05 Nov 2020
Cited by 117 | Viewed by 8510
Abstract
Solubility, bioavailability, permeation, polymorphism, and stability concerns associated to solid-state pharmaceuticals demand for effective solutions. To overcome some of these drawbacks, ionic liquids (ILs) have been investigated as solvents, reagents, and anti-solvents in the synthesis and crystallization of active pharmaceutical ingredients (APIs), as [...] Read more.
Solubility, bioavailability, permeation, polymorphism, and stability concerns associated to solid-state pharmaceuticals demand for effective solutions. To overcome some of these drawbacks, ionic liquids (ILs) have been investigated as solvents, reagents, and anti-solvents in the synthesis and crystallization of active pharmaceutical ingredients (APIs), as solvents, co-solvents and emulsifiers in drug formulations, as pharmaceuticals (API-ILs) aiming liquid therapeutics, and in the development and/or improvement of drug-delivery-based systems. The present review focuses on the use of ILs in the pharmaceutical field, covering their multiple applications from pharmaceutical synthesis to drug delivery. The most relevant research conducted up to date is presented and discussed, together with a critical analysis of the most significant IL-based strategies in order to improve the performance of therapeutics and drug delivery systems. Full article
(This article belongs to the Special Issue Ionic Liquids in Drug Development, Formulation, and Delivery)
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Other

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16 pages, 1309 KiB  
Perspective
Are Myths and Preconceptions Preventing Us from Applying Ionic Liquid Forms of Antiviral Medicines to the Current Health Crisis?
by Julia L. Shamshina and Robin D. Rogers
Int. J. Mol. Sci. 2020, 21(17), 6002; https://doi.org/10.3390/ijms21176002 - 20 Aug 2020
Cited by 17 | Viewed by 3098
Abstract
At the moment, there are no U.S. Food and Drug Administration (U.S. FDA)-approved drugs for the treatment of COVID-19, although several antiviral drugs are available for repurposing. Many of these drugs suffer from polymorphic transformations with changes in the drug’s safety and efficacy; [...] Read more.
At the moment, there are no U.S. Food and Drug Administration (U.S. FDA)-approved drugs for the treatment of COVID-19, although several antiviral drugs are available for repurposing. Many of these drugs suffer from polymorphic transformations with changes in the drug’s safety and efficacy; many are poorly soluble, poorly bioavailable drugs. Current tools to reformulate antiviral APIs into safer and more bioavailable forms include pharmaceutical salts and cocrystals, even though it is difficult to classify solid forms into these regulatory-wise mutually exclusive categories. Pure liquid salt forms of APIs, ionic liquids that incorporate APIs into their structures (API-ILs) present all the advantages that salt forms provide from a pharmaceutical standpoint, without being subject to solid-state matter problems. In this perspective article, the myths and the most voiced concerns holding back implementation of API-ILs are examined, and two case studies of API-ILs antivirals (the amphoteric acyclovir and GSK2838232) are presented in detail, with a focus on drug property improvement. We advocate that the industry should consider the advantages of API-ILs which could be the genesis of disruptive innovation and believe that in order for the industry to grow and develop, the industry should be comfortable with a certain element of risk because progress often only comes from trying something different. Full article
(This article belongs to the Special Issue Ionic Liquids in Drug Development, Formulation, and Delivery)
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