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Pharmaceutics
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Multifunctional Bioinorganic Metal Ions in Pharmaceutical Applications
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Multifunctional Bioinorganic Metal Ions in Pharmaceutical Applications

A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Drug Targeting and Design".

Deadline for manuscript submissions: closed (20 December 2022) | Viewed by 15032

Special Issue Editors

Dr. Ciara M Murphy

E-Mail Website
Guest Editor
Tissue Engineering Research Group, Department of Anatomy and Regenerative Medicine, Royal College of Surgeons in Ireland, 123 St Stephens Green, Dublin 2, Ireland
Interests: bio-responsive biomaterials; bone regeneration; targeted therapeutic delivery systems; metabolic bone disease
Dr. Kulwinder Kaur

E-Mail Website
Guest Editor
Tissue Engineering Research Group, Department of Anatomy and Regenerative Medicine, Royal College of Surgeons in Ireland, 123 St Stephens Green, Dublin 2, Ireland
Interests: injectable hydrogels; mechanically robust biomaterials; materials Science; bone regeneration; metabolic bone disease

Special Issue Information

Dear Colleagues,

In this Special Issue entitled “Multifunctional Bioinorganic Metal Ions in Pharmaceutical Applications”, we aim to explore the potential and diversity of bioinorganic metal ions for the preparation of small molecule therapeutics, novel regenerative medicines, gene therapy, biological imaging and drug delivery agents. The growing field of bioinorganic metal ions has expanded the knowledge of their role in up-/down-regulating cellular functions and biological processes, as well as in the onset and progression of different pathologies. Due to the wide physical and biological properties of bioinorganic metal ions, their use in a wide variety of platforms has emerged as promising strategies in improving human health with important contributions in medical, regenerative and pharmaceutical science. This Special Issue aims to provide insight into the cutting-edge developments in the controlled and sustained therapeutic potential of bioinorganic metal ions for pharmaceutical/biological applications. Altogether, starting from a deep insight into basic aspects, this issue aims to highlight the new advances in “metals in pharmaceutical applications” in the form of original research papers and review articles.

Dr. Ciara M Murphy
Dr. Kulwinder Kaur
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. 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

  • bioinorganic metal ions
  • drug delivery
  • regenerative medicine
  • controlled release

Published Papers (5 papers)

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Research

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21 pages, 5961 KiB  
Article
A Degradable and Osteogenic Mg-Based MAO-MT-PLGA Drug/Ion Delivery System for Treating an Osteoporotic Fracture
by Changxin Liu, Wen Zhang, Ming Gao, Ke Yang, Lili Tan and Wei Zhao
Pharmaceutics 2022, 14(7), 1481; https://doi.org/10.3390/pharmaceutics14071481 - 16 Jul 2022
Cited by 3 | Viewed by 2044
Abstract
Osteoporotic fractures are a very common bone disease that is difficult to completely cure. A large number of people worldwide suffer from pain caused by osteoporotic fractures every year, which can even cause disability and death. The compromised skeletal strength, lower density, trabecular [...] Read more.
Osteoporotic fractures are a very common bone disease that is difficult to completely cure. A large number of people worldwide suffer from pain caused by osteoporotic fractures every year, which can even cause disability and death. The compromised skeletal strength, lower density, trabecular microstructure, and bone-forming ability caused by osteoporotic fractures make them difficult to treat relative to normal fractures. An ideal scheme for osteoporotic fractures is to select internal fixation materials with matched mechanical and biological properties and carry anti-osteoporosis drugs on the plant to achieve bio-fixation and improve the condition of osteoporosis simultaneously. We designed a Mg-based MAO-MT-PLGA drug/ion delivery system (DDS) compatible with bone-like mechanical properties, degradation properties, and drug therapy. In this research, we evaluated the degradation behavior of Mg-based MAO-MT-PLGA DDS using immersion tests and electrochemical tests aided by SEM, EDS, XPS, XRD, and FT-IR. The DDS showed better corrosion resistance over Mg alloy and could release more Mg2+ due to the degradation of PLGA. According to cell viability and cell adhesion, the DDS showed better osteogenic characteristics over control group I (Mg alloy) and control group II (Mg-based MAO alloy), especially in the cells co-cultured with the leaching solution for 72 h, in which the DDS group increased to about 15% cell viability compared with group I (p < 0.05). The mRNA relative expressions, including ALP, collagen I, OCN, OPG, and Runx-2, as well as extracellular matrix calcium deposits of the DDS, are 1.5~2 times over control group I and control group II (p < 0.05), demonstrating a better ability to promote bone formation and inhibit bone resorption. After the DDS was implanted into the castrated rat model for one month, the trabeculae in the treatment group were significantly denser and stronger than those in the control group, with a difference of about 1.5 times in bone volume fraction, bone density, and the number of trabeculae, as well as the magnesium content in the bone tissue (p < 0.05). The above results demonstrated that the Mg-based MAO-MT-PLGA drug/ion delivery system is a potential treatment for osteoporotic fractures. Full article
(This article belongs to the Special Issue Multifunctional Bioinorganic Metal Ions in Pharmaceutical Applications)
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13 pages, 4645 KiB  
Article
Hydroxychloroquine Does Not Function as a Direct Zinc Ionophore
by Oisín N. Kavanagh, Shayon Bhattacharya, Luke Marchetti, Robert Elmes, Finbarr O’Sullivan, John P. Farragher, Shane Robinson, Damien Thompson and Gavin M. Walker
Pharmaceutics 2022, 14(5), 899; https://doi.org/10.3390/pharmaceutics14050899 - 20 Apr 2022
Cited by 4 | Viewed by 3875
Abstract
Drug-mediated correction of abnormal biological zinc homeostasis could provide new routes to treating neurodegeneration, cancer, and viral infections. Designing therapeutics to facilitate zinc transport intracellularly is hampered by inadequate concentrations of endogenous zinc, which is often protein-bound in vivo. We found strong evidence [...] Read more.
Drug-mediated correction of abnormal biological zinc homeostasis could provide new routes to treating neurodegeneration, cancer, and viral infections. Designing therapeutics to facilitate zinc transport intracellularly is hampered by inadequate concentrations of endogenous zinc, which is often protein-bound in vivo. We found strong evidence that hydroxychloroquine, a drug used to treat malaria and employed as a potential treatment for COVID-19, does not bind and transport zinc across biological membranes through ionophoric mechanisms, contrary to recent claims. In vitro complexation studies and liposomal transport assays are correlated with cellular zinc assays in A549 lung epithelial cells to confirm the indirect mechanism of hydroxychloroquine-mediated elevation in intracellular zinc without ionophorism. Molecular simulations show hydroxychloroquine-triggered helix perturbation in zinc-finger protein without zinc chelation, a potential alternative non-ionophoric mechanism. Full article
(This article belongs to the Special Issue Multifunctional Bioinorganic Metal Ions in Pharmaceutical Applications)
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21 pages, 2820 KiB  
Article
Cyclooxygenase-Inhibiting Platinum(IV) Prodrugs with Potent Anticancer Activity
by Aleen Khoury, Jennette A. Sakoff, Jayne Gilbert, Kieran F. Scott, Shawan Karan, Christopher P. Gordon and Janice R. Aldrich-Wright
Pharmaceutics 2022, 14(4), 787; https://doi.org/10.3390/pharmaceutics14040787 - 3 Apr 2022
Cited by 16 | Viewed by 2895
Abstract
Platinum(IV) prodrugs of the [Pt(PL)(AL)(COXi)(OH)]2+ type scaffold (where PL is 1,10-phenanthroline or 5,6-dimethyl-1,10-phenanthroline, AL is 1S,2S-diaminocyclohexane, and COXi is a COX inhibitor, either indomethacin or aspirin) were synthesised and characterised, and their [...] Read more.
Platinum(IV) prodrugs of the [Pt(PL)(AL)(COXi)(OH)]2+ type scaffold (where PL is 1,10-phenanthroline or 5,6-dimethyl-1,10-phenanthroline, AL is 1S,2S-diaminocyclohexane, and COXi is a COX inhibitor, either indomethacin or aspirin) were synthesised and characterised, and their biological activity was explored. MTT assays showed that these complexes exhibit outstanding activity against a range of cancer cell lines, and nanomolar activities were observed. The most potent complex, 4, exhibited a GI50 of 3 nM in the Du145 prostate cancer cell line and was observed to display a 1614-fold increased activity against the HT29 colon cancer cell line relative to cisplatin. ICP-MS studies showed a linear correlation between increased cellular accumulation of the complexes and increased cytotoxicity, while an enzyme immunoassay showed that 1 and 2 inhibited COX-2 at 14 and 1.4 µM, respectively, which is comparable to the inhibition exhibited by indomethacin. These results suggest that while the cytotoxicity of prodrugs 1–4 was influenced by cellular uptake, it was not entirely dependent on either COX inhibition or lipophilicity. Full article
(This article belongs to the Special Issue Multifunctional Bioinorganic Metal Ions in Pharmaceutical Applications)
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15 pages, 3724 KiB  
Article
Facile Synthesis of Gallium (III)-Chitosan Complexes as Antibacterial Biomaterial
by Muhammad Asim Akhtar, Zoya Hadzhieva, Kanwal Ilyas, Muhammad Saad Ali, Wolfgang Peukert and Aldo R. Boccaccini
Pharmaceutics 2021, 13(10), 1702; https://doi.org/10.3390/pharmaceutics13101702 - 15 Oct 2021
Cited by 7 | Viewed by 2018
Abstract
Even though antibiotic treatment remains one of the most common tools to handle bacterial infections, the excessive antibiotic concentration at the target site may lead to undesired effects. Aiming at the fabrication of antibiotic-free biomaterials for antibacterial applications, in this work, we propose [...] Read more.
Even though antibiotic treatment remains one of the most common tools to handle bacterial infections, the excessive antibiotic concentration at the target site may lead to undesired effects. Aiming at the fabrication of antibiotic-free biomaterials for antibacterial applications, in this work, we propose the synthesis of gallium (III)—chitosan (Ga (III)-CS) complexes with six different gallium concentrations via an in situ precipitation method. Fourier Transform infrared spectroscopy indicated the chelation of chitosan with Ga (III) by peak shifts and changes in the relative absorbance of key spectral bands, while energy-dispersive X-ray spectroscopy indicated the homogenous distribution of the metal ions within the polymer matrix. Additionally, similar to CS, all Ga (III)-CS complexes showed hydrophobic behavior during static contact-angle measurements. The antibacterial property of the complexes against both Gram-negative and Gram-positive bacteria was positively correlated with the Ga (III) concentration. Moreover, cell studies confirmed the nontoxic behavior of the complexes against the human osteosarcoma cell line (MG-63 cells) and mouse embryonic fibroblasts cell line (MEFs). Based on the results of this study, new antibiotic-free antibacterial biomaterials based on Ga (III)-CS can be developed, expanding the scope of CS applications in the biomedical field. Full article
(This article belongs to the Special Issue Multifunctional Bioinorganic Metal Ions in Pharmaceutical Applications)
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Review

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22 pages, 17488 KiB  
Review
Advantageous Reactivity of Unstable Metal Complexes: Potential Applications of Metal-Based Anticancer Drugs for Intratumoral Injections
by Aviva Levina, Debbie C. Crans and Peter A. Lay
Pharmaceutics 2022, 14(4), 790; https://doi.org/10.3390/pharmaceutics14040790 - 4 Apr 2022
Cited by 16 | Viewed by 2948
Abstract
Injections of highly cytotoxic or immunomodulating drugs directly into the inoperable tumor is a procedure that is increasingly applied in the clinic and uses established Pt-based drugs. It is advantageous for less stable anticancer metal complexes that fail administration by the standard intravenous [...] Read more.
Injections of highly cytotoxic or immunomodulating drugs directly into the inoperable tumor is a procedure that is increasingly applied in the clinic and uses established Pt-based drugs. It is advantageous for less stable anticancer metal complexes that fail administration by the standard intravenous route. Such hydrophobic metal-containing complexes are rapidly taken up into cancer cells and cause cell death, while the release of their relatively non-toxic decomposition products into the blood has low systemic toxicity and, in some cases, may even be beneficial. This concept was recently proposed for V(V) complexes with hydrophobic organic ligands, but it can potentially be applied to other metal complexes, such as Ti(IV), Ga(III) and Ru(III) complexes, some of which were previously unsuccessful in human clinical trials when administered via intravenous injections. The potential beneficial effects include antidiabetic, neuroprotective and tissue-regenerating activities for V(V/IV); antimicrobial activities for Ga(III); and antimetastatic and potentially immunogenic activities for Ru(III). Utilizing organic ligands with limited stability under biological conditions, such as Schiff bases, further enhances the tuning of the reactivities of the metal complexes under the conditions of intratumoral injections. However, nanocarrier formulations are likely to be required for the delivery of unstable metal complexes into the tumor. Full article
(This article belongs to the Special Issue Multifunctional Bioinorganic Metal Ions in Pharmaceutical Applications)
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