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Pharmaceutics
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Ionic Liquids in Pharmaceutical and Biomedical Applications, 2nd Edition
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Ionic Liquids in Pharmaceutical and Biomedical Applications, 2nd Edition

A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Physical Pharmacy and Formulation".

Deadline for manuscript submissions: 30 May 2025 | Viewed by 10475

Special Issue Editor

Dr. Roksana Markiewicz

E-Mail Website
Guest Editor
NanoBioMedical Centre, Adam Mickiewicz University, Wszechnicy Piastowskiej 3, 61-614 Poznan, Poland
Interests: ionic liquids; nanodrug delivery; chemical engineering; green chemistry; biopolymers; polymer nanomaterials; synthesis; nanomaterials; material characterization; polymeric materials; nanomaterials synthesis; nanoparticle synthesis; polymerization
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

It is my great pleasure to invite you to contribute research or review articles to a Special Issue of Pharmaceutics entitled “Ionic Liquids in Pharmaceutical and Biomedical Applications, 2nd Edition”. The application of ionic liquids (ILs) and deep eutectic solvents (DESs) in the biomedical sphere has recently gained increasing attention, mainly due to their unique properties and tunability, which allow for the development of materials with specific functions that can meet appropriate requirements. In the areas of pharmaceutics and biomedicine, ILs and DESs have already been used as active pharmaceutical ingredients and drug delivery systems, including nanoformulations. Moreover, their unique properties allow them to be used as antimicrobial, antifungal, and antiviral agents, as stabilizers for both drugs and proteins, and in biosensing applications.

This Special Issue aims to present recent trends and developments, including discussions about fundamental aspects and their applicability. Moreover, it will allow us to identify current challenges and future directions in the use of ionic liquids and deep eutectic solvents in pharmaceutics and biomedicine.

Original research papers and review articles are welcome.

We look forward to receiving your contributions.

Dr. Roksana Markiewicz
Guest Editor

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. Pharmaceutics is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). 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
  • active pharmaceutical ingredients (API)
  • drug delivery systems
  • antimicrobial properties
  • drug and protein stabilization
  • nanoformulations
  • biosensing

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Related Special Issue

Published Papers (4 papers)

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Research

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37 pages, 10656 KiB  
Article
Synthesis, Characterisation, and In Vitro Evaluation of Biocompatibility, Antibacterial and Antitumor Activity of Imidazolium Ionic Liquids
by Elisabetta Novello, Giuseppina Scalzo, Giovanni D’Agata, Maria G. Raucci, Luigi Ambrosio, Alessandra Soriente, Barbara Tomasello, Cristina Restuccia, Lucia Parafati, Grazia M. L. Consoli, Loredana Ferreri, Antonio Rescifina, Chiara Zagni and Daniela C. Zampino
Pharmaceutics 2024, 16(5), 642; https://doi.org/10.3390/pharmaceutics16050642 - 10 May 2024
Cited by 1 | Viewed by 1757
Abstract
In recent decades, ionic liquids (ILs) have garnered research interest for their noteworthy properties, such as thermal stability, low or no flammability, and negligible vapour pressure. Moreover, their tunability offers limitless opportunities to design ILs with properties suitable for applications in many industrial [...] Read more.
In recent decades, ionic liquids (ILs) have garnered research interest for their noteworthy properties, such as thermal stability, low or no flammability, and negligible vapour pressure. Moreover, their tunability offers limitless opportunities to design ILs with properties suitable for applications in many industrial fields. This study aims to synthetise two series of methylimidazolium ILs bearing long alkyl chain in their cations (C9, C10, C12, C14, C16, C18, C20) and with tetrafluoroborate (BF4) and the 1,3-dimethyl-5-sulfoisophthalate (DMSIP) as counter ions. The ILs were characterised using 1H-NMR and MALDI-TOF, and their thermal behaviour was investigated through DSC and TGA. Additionally, the antimicrobial, anticancer, and cytotoxic activities of the ILs were analysed. Moreover, the most promising ILs were incorporated at different concentrations (0.5, 1, 5 wt%) into polyvinyl chloride (PVC) by solvent casting to obtain antimicrobial blend films. The thermal properties and stability of the resulting PVC/IL films, along with their hydrophobicity/hydrophilicity, IL surface distribution, and release, were studied using DSC and TGA, contact angle (CA), SEM, and UV–vis spectrometry, respectively. Furthermore, the antimicrobial and cytotoxic properties of blends were analysed. The in vitro results demonstrated that the antimicrobial and antitumor activities of pure ILs against t Listeria monocytogenes, Escherichia coli, Pseudomonas fluorescens strains, and the breast cancer cell line (MCF7), respectively, were mainly dependent on their structure. These activities were higher in the series containing the BF4 anion and increased with the increase in the methylimidazolium cation alkyl chain length. However, the elongation of the alkyl chain beyond C16 induced a decrease in antimicrobial activity, indicating a cut-off effect. A similar trend was also observed in terms of in vitro biocompatibility. The loading of both the series of ILs into the PVC matrix did not affect the thermal stability of PVC blend films. However, their Tonset decreased with increased IL concentration and alkyl chain length. Similarly, both the series of PVC/IL films became more hydrophilic with increasing IL concentration and alkyl chain. The loading of ILs at 5% concentration led to considerable IL accumulation on the blend film surfaces (as observed in SEM images) and, subsequently, their higher release. The biocompatibility assessment with healthy human dermal fibroblast (HDF) cells and the investigation of antitumoral properties unveiled promising pharmacological characteristics. These findings provide strong support for the potential utilisation of ILs in biomedical applications, especially in the context of cancer therapy and as antibacterial agents to address the challenge of antibiotic resistance. Furthermore, the unique properties of the PVC/IL films make them versatile materials for advancing healthcare technologies, from drug delivery to tissue engineering and antimicrobial coatings to diagnostic devices. Full article
(This article belongs to the Special Issue Ionic Liquids in Pharmaceutical and Biomedical Applications, 2nd Edition)
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20 pages, 2872 KiB  
Article
Tuning of the Anti-Breast Cancer Activity of Betulinic Acid via Its Conversion to Ionic Liquids
by Paula Ossowicz-Rupniewska, Joanna Klebeko, Irina Georgieva, Sonia Apostolova, Łukasz Struk, Svetla Todinova, Rumiana Dimitrova Tzoneva and Maya Guncheva
Pharmaceutics 2024, 16(4), 496; https://doi.org/10.3390/pharmaceutics16040496 - 3 Apr 2024
Cited by 2 | Viewed by 1540
Abstract
Betulinic acid (BA) is a natural pentacyclic triterpene with diverse biological activities. However, its low water solubility limits its pharmaceutical application. The conversion of pharmaceutically active molecules into ionic liquids (ILs) is a promising strategy to improve their physicochemical properties, stability, and/or potency. [...] Read more.
Betulinic acid (BA) is a natural pentacyclic triterpene with diverse biological activities. However, its low water solubility limits its pharmaceutical application. The conversion of pharmaceutically active molecules into ionic liquids (ILs) is a promising strategy to improve their physicochemical properties, stability, and/or potency. Here, we report the synthesis and characterization of 15 novel ILs containing a cation ethyl ester of a polar, non-polar, or charged amino acid [AAOEt] and an anion BA. Except for [ValOEt][BA], we observed preserved or up to 2-fold enhanced cytotoxicity toward hormone-dependent breast cancer cells MCF-7. The estimated IC50 (72 h) values within the series varied between 4.8 and 25.7 µM. We found that the most cytotoxic IL, [LysOEt][BA]2, reduced clonogenic efficiency to 20% compared to that of BA. In addition, we evaluated the effect of a 72 h treatment with BA or [LysOEt][BA]2, the most cytotoxic compound, on the thermodynamic behavior of MCF-7 cells. Based on our data, we suggest that the charged amino acid lysine included in the novel ILs provokes cytotoxicity by a mechanism involving alteration in membrane lipid organization, which could be accompanied by modulation of the visco–elastic properties of the cytoplasm. Full article
(This article belongs to the Special Issue Ionic Liquids in Pharmaceutical and Biomedical Applications, 2nd Edition)
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14 pages, 5326 KiB  
Article
Piperacillin/Tazobactam Co-Delivery by Micellar Ionic Conjugate Systems Carrying Pharmaceutical Anions and Encapsulated Drug
by Katarzyna Niesyto, Aleksy Mazur and Dorota Neugebauer
Pharmaceutics 2024, 16(2), 198; https://doi.org/10.3390/pharmaceutics16020198 - 30 Jan 2024
Cited by 3 | Viewed by 1444
Abstract
Previously obtained amphiphilic graft copolymers based on [2-(methacryloyloxy)ethyl]trimethylammonium chloride (TMAMA) ionic liquid were used as the matrices of three types of nanocarriers, i.e., conjugates with ionic piperacillin (PIP) and micelles with tazobactam (TAZ), which represented single systems, and dual systems bearing PIP anions [...] Read more.
Previously obtained amphiphilic graft copolymers based on [2-(methacryloyloxy)ethyl]trimethylammonium chloride (TMAMA) ionic liquid were used as the matrices of three types of nanocarriers, i.e., conjugates with ionic piperacillin (PIP) and micelles with tazobactam (TAZ), which represented single systems, and dual systems bearing PIP anions and encapsulated TAZ for co-delivery. The exchange of Cl anions in TMAMA units with PIP ones resulted in a yield of 45.6–72.7 mol.%. The self-assembling properties were confirmed by the critical micelle concentration (CMC), which, after ion exchange, increased significantly (from 0.011–0.020 mg/mL to 0.041–0.073 mg/mL). The amphiphilic properties were beneficial for TAZ encapsulation to reach drug loading contents (DLCs) in the ranges of 37.2–69.5 mol.% and 50.4–80.4 mol.% and to form particles with sizes of 97–319 nm and 24–192 nm in the single and dual systems, respectively. In vitro studies indicated that the ionically conjugated drug (PIP) was released in quantities of 66–81% (7.8–15.0 μg/mL) from single-drug systems and 21–25% (2.6–3.9 μg/mL) from dual-drug systems. The release of encapsulated TAZ was more efficient, achieving 47–98% (7.5–9.0 μg/mL) release from the single systems and 47–69% (9.6–10.4 μg/mL) release from the dual ones. Basic cytotoxicity studies showed non-toxicity of the polymer matrices, while the introduction of the selected drugs induced cytotoxicity against normal human bronchial epithelial cells (BEAS-2B) with the increase in concentration. Full article
(This article belongs to the Special Issue Ionic Liquids in Pharmaceutical and Biomedical Applications, 2nd Edition)
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Review

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29 pages, 3121 KiB  
Review
Ionic Liquids in Pharmaceutical and Biomedical Applications: A Review
by Yue Zhuo, He-Li Cheng, Yong-Gang Zhao and Hai-Rong Cui
Pharmaceutics 2024, 16(1), 151; https://doi.org/10.3390/pharmaceutics16010151 - 22 Jan 2024
Cited by 19 | Viewed by 5022
Abstract
The unique properties of ionic liquids (ILs), such as structural tunability, good solubility, chemical/thermal stability, favorable biocompatibility, and simplicity of preparation, have led to a wide range of applications in the pharmaceutical and biomedical fields. ILs can not only speed up the chemical [...] Read more.
The unique properties of ionic liquids (ILs), such as structural tunability, good solubility, chemical/thermal stability, favorable biocompatibility, and simplicity of preparation, have led to a wide range of applications in the pharmaceutical and biomedical fields. ILs can not only speed up the chemical reaction process, improve the yield, and reduce environmental pollution but also improve many problems in the field of medicine, such as the poor drug solubility, product crystal instability, poor biological activity, and low drug delivery efficiency. This paper presents a systematic and concise analysis of the recent advancements and further applications of ILs in the pharmaceutical field from the aspects of drug synthesis, drug analysis, drug solubilization, and drug crystal engineering. Additionally, it explores the biomedical field, covering aspects such as drug carriers, stabilization of proteins, antimicrobials, and bioactive ionic liquids. Full article
(This article belongs to the Special Issue Ionic Liquids in Pharmaceutical and Biomedical Applications, 2nd Edition)
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