RSC Advances Blog

We are very pleased to introduce Saurabh Das, the corresponding author of the paper ‘A Zn^II complex of ornidazole with decreased nitro radical anions that is still highly active on Entamoeba histolytica‘. His article has been very well received and handpicked by our reviewers and handling editors as one of our June HOT articles.  Saurabh was kind enough to tell us more about the work that went into this article and what he hopes to achieve in the future. You can find out more about the author and their article below and find more HOT articles in our online collection.

Meet the Author

Saurabh Das completed his bachelor’s degree with honours in Chemistry from Presidency College in 1990, then affiliated to University of Calcutta. His Master’s with specialization in Inorganic Chemistry was done at the University College of Science, University of Calcutta in 1992. He received his PhD from University of Calcutta in 2000 having worked at the Chemical Sciences Division of Saha Institute of Nuclear Physics (Ph D Supervisor: Prof. Parikshit C Mandal). After two years of teaching at the Calcutta International School, Kolkata (1998-2000), five and a half years of teaching at the Department of Chemistry, Bejoy Narayan Mahavidyalaya, Hooghly (under University of Burdwan) (2000-2006) he joined the Department of Chemistry, Jadavpur University in January, 2006.

He is now a Professor with research interests in modulating the generation of reactive intermediates of different drugs forming inorganic complexes to strike a balance between efficacy and adverse effects; and offshoots of that general theme. He has 66 publications in peer reviewed international journals.

The research team:

Ms Neha Banyal (left photo) and Professor Kasturi Mukhopadhyay (right photo)

Professor Saurabh Das and Ms Promita Nandy (left photo) and Professor Sanjay Kumar and Mr Soumen Singha (right photo)

Could you briefly explain the focus of your article to the non-specialist (in one or two sentences only) and why it is of current interest?
The molecule (Ornidazole) is a drug belonging to the 5-nitroimidazole family that is used to treat bacterial and/or parasitic infections. The performance of the drug depends on the generation of an intermediate (the nitro radical-anion) that kills disease causing microbes. The same intermediate is neurotoxic to the host (i.e. the system affected by disease causing microbes) upon prolonged use. Hence, controlling the generation of the nitro-radical anion is essential to strike a balance between efficacy and neurotoxic side effects.

How big an impact could your results potentially have?
The results should have a good impact since we worked with a compound that is already established as a drug and is part of a number of pharmaceutical formulations. The modified compound, i. e. the zinc complex needs to be tried in vivo, in living systems in order to identify the extent of difference between the work performed by in the laboratory (on model systems) and what the results would be on living systems. Experts would understand and realize here that a certain difference would exist which needs to be identified.

Could you explain the motivation behind this study?
The motivation of the study was to strike a balance between efficacy and neurotoxic side effects for this family of drugs. For most drugs, intermediates involved with the drug’s efficacy are its problems as well. If they can be separated, then one can either increase cure for an accepted level of complication or decrease complications for an accepted level of cure.

In your opinion, what are the key design considerations for your study?
Modification of Ornidazole (the drug) in a manner that generation of nitro-radical anion is controlled, i.e, modulated. For our study, this was achieved through complex formation with Zn(II).

Which part of the work towards this paper proved to be most challenging?
There were three aspects to the study i) preparation of the complex and its characterization,, ii) showing that generation of nitro-radical anion is less for the complex which we followed by an enzyme assay and iii) inspite of decrease in nitro-radical anion formation, the complex showed the same efficacy on amoeba, as that observed for Ornidazole. A combination of these three aspects performed through suitable experiments suggest decrease in the formation of the nitro radical-anion should decrease neurotoxicity on the host (although we did not verify this in our study) but it should happen since studies earlier to ours have linked neurotoxicity to nitro radical-anion formation. Simultaneously, bacteria or parasite killing should also be affected which in our case did not happen. The complex maintained its killing efficacy of amoeba even with decreased nitro radical-anion; being as good as Ornidazole. This we attributed to aspects related to complex formation. We showed one such attribute of the complex in our study, that of it being able to bind DNA better than Ornidazole. So it’s really a culmination of different experiments we performed.

What aspect of your work are you most excited about at the moment?
The fact modification of Ornidazole through complex formation with Zn(II) could increase its therapeutic index (T I) where T I = TD₅₀/ED₅₀; TD₅₀ implies toxic dose in 50% of subjects and ED₅₀ implies effective dose for 50% of population. The larger the T I, safer the drug. Besides, Zn being relatively non-toxic unlike other metal ions and since there is use for it in the bio-system, it should not be harmful if it goes into our bodies

What is the next step? What work is planned?
I have not really thought about it. Since the manuscript has been well received I will have to speak to one of my collaborators (Prof. Kasturi Mukhopadhyay of School of Environmental Sciences at the Jawaharlal Nehru University, New Delhi) in whose laboratory the biological experiments were performed, if she could take the Zn(II) complex forward and do few more studies with it that reveal its mechanism of action on bacteria and amoeba strains; may be try on different bacterial strains, while we perform more model studies to search for other attributes of complex formation. After these are done a sharing of data on biological experiments for mechanism of action and model studies performed (by us) could be useful to see for ourselves whether they correct to each other or establish a difference of opinion.

A Zn^II complex of ornidazole with decreased nitro radical anions that is still highly active on Entamoeba histolytica
Promita Nandy, Soumen Singha, Neha Banyal, Sanjay Kumar, Kasturi Mukhopadhyay and Saurabh Das
RSC Adv., 2020,10, 23286-23296
DOI: 10.1039/D0RA02597F, Paper

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We are very pleased to introduce Shine (Xu) Zhang, the corresponding author of the paper ‘A simple and cost-effective approach to fabricate tunable length polymeric microneedle patches for controllable transdermal drug delivery‘. His article has been very well received and handpicked by our reviewers and handling editors as one of our May HOT articles.  Shine was kind enough to tell us more about the work that went into this article and what he hopes to achieve in the future. You can find out more about the author and their article below and find more HOT articles in our online collection.

Meet the Author

Dr. Shine (Xu) Zhang holds the Canada Research Chair (Tier II) in Healthy Environments and Communities in the Department of Chemistry and Department of Health Sciences at Cape Breton University, Pearl River Scholar Guest Chair Professor of Pharmacy at Shenzhen Polytechnic, and an active member of Beatrice Hunter Cancer Research Institute. His research aims at exploiting nanotechnology for health and environmental applications with focus on cancer diagnostics and treatment with precision nanomedicine. He is developing theranostic nanosystems for targeted combinatory therapy with his expertise in DNA aptamer technology, nanocomposite materials, polymeric microneedles, surface chemistry, surface-enhanced Raman spectroscopy, and reactive oxygen species chemistry (Fenton chemistry). Since 2015, Dr. Zhang has trained >50 postdoctoral fellows and research students, who obtained >25 prestigious scholarships and awards.

Dr. Zhang graduated with a PhD (Analytical Chemistry) from the University of Waterloo, followed with postdoctoral training at the University of Waterloo and Harvard University funded by fellowships from the Ontario Ministry of Research and Innovation and the Canadian Institutes of Health Research.

Team picture

Could you briefly explain the focus of your article to the non-specialist (in one or two sentences only) and why it is of current interest?
Dissolvable polymeric microneedles are micron-sized needles for delivering drugs through the outermost layer of skin for either rapid or prolonged release. This method is painless, can be self-administered, and does not require stringent storage conditions, which increases the availability and distribution of sensitive drug molecules. We simplified the microneedle manufacturing process by modifying widely available tattoo needle cartridges as master templates, reducing manufacturing time and cost and enabling researchers to develop microneedles of various formulations for proof-of-concept studies.

How big an impact could your results potentially have?
Microneedles can be manufactured in many ways that are generally costly, and most moulding techniques only generate a single array morphology. We demonstrated that simple and inexpensive tattoo cartridges can be modified for manufacturing microneedles of desired length by applying a simple silicone spacer. This simplifies the procedure and enables low cost construction of these devices, which facilitates research and development in this field.

Could you explain the motivation behind this study?
Transdermal drug delivery is an attractive alternative to traditional subcutaneous, intramuscular, and intravenous injection; however, the outer layer skin is an effective barrier towards macromolecular and hydrophilic drugs. Microneedles penetrate the skin barrier, stabilize embedded drug molecules toward thermal and hydrolytic degradation, and facilitate distribution in remote and resource limited areas. They reduce burdens on healthcare systems and enable effective drug distribution to remote communities.

In your opinion, what are the key design considerations for your study?
The key design considerations in this work were maintaining the morphological stability of the microneedles to ensure they remained rigid enough to penetrate the skin while also dissolving quickly within the skin tissue and delivering its drug cargo.

Which part of the work towards this paper proved to be most challenging?
High uniformity in morphology and geometry is required to ensure accurate and precise drug delivery. This was a challenge when preparing microneedles from different master templates and batches, including varying microneedle length using the same master template.

What aspect of your work are you most excited about at the moment?
The most exciting aspect of this work is its general applicability. Many modifications can be made, including incorporation of photothermal nanomaterials to enable precisely controlled drug release through controlled dissolution of the structural polymers.

What is the next step? What work is planned?
Our goal is the large-scale microneedle fabrication for the delivery of active biologics, e.g., proteins, vaccines, and siRNA. This technology may facilitate disease treatment and prevention, especially in areas with limited resources and healthcare availability.

A simple and cost-effective approach to fabricate tunable length polymeric microneedle patches for controllable transdermal drug delivery
Yongli Chen, Yiwen Xian, Andrew J. Carrier, Brian Youden, Mark Servos, Shufen Cui, Tiangang Luan, Sujing Lin and Xu Zhang
RSC Adv., 2020,10, 15541-15546
DOI: 10.1039/D0RA01382J, Paper

Submit to RSC Advances today! Check out our author guidelines for information on our article types or find out more about the advantages of publishing in a Royal Society of Chemistry journal.

Keep up to date with our latest HOT articles, Reviews, Collections & more by following us on Twitter. You can also keep informed by signing up to our E-Alerts.

We are very pleased to introduce Irene Maier, the corresponding author of the paper ‘Mannosylated hemagglutinin peptides bind cyanovirin-N independent of disulfide-bonds in complementary binding sites‘. Her article has been very well received and handpicked by our reviewers and handling editors as one of our May HOT articles. Irene was kind enough to tell us more about the work that went into this article and what she hopes to achieve in the future. You can find out more about the author and their article below and find more HOT articles in our online collection.

Meet the Author

Irene is working as a researcher at the University of California, Los Angeles (UCLA). She graduated from the University of Vienna and was awarded an international L’Oréal-UNESCO fellowship for her work on the development of an optical immunochip biosensor for rapid allergen detection in complex food matrices and allergy diagnosis. She is interested in the molecular understanding of immune diseases and emphasizes studies on the interactions between immunoglobulin-like protein structures and antigens.

Irene did a postdoc at Caltech before she changed to UCLA. In her postdoctoral work with the National Aeronautics and Space Administration (NASA) Agency, she started broad cancer research projects with a team of collaborators committed to high-level space biology. As a biochemist by training, Irene designed and organized radiation experiments in preclinical studies to be performed at the NASA Space Research Laboratory, a high-tech synchrotron service institution for basic and applied science in Upton, NY.  Her science has been aiming at establishing networks to implement new microbiota-related biomarkers for the assessment of side-effects and adverse events in radiation therapy. She recently returned to the Medical University of Vienna, where she is continuing research on radiation-induced intestinal microbiota-compositions that alter bone loss.

Could you briefly explain the focus of your article to the non-specialist (in one or two sentences only) and why it is of current interest?
We chemically synthesized mono- and di-mannosylated influenza glycoprotein peptides, mimicking naturally found N (asparagine)-linked N-acetyl glucosamine and high-mannose oligosaccharides on the surface of viruses that cause life-threatening viral infections. A comparison of predicted N-glycosylation sites on spike glycoproteins of Wuhan-Hu-1–2019 novel coronavirus (2019-nCoV) and severe acute respiratory syndrome coronavirus-2003 (SARS-CoV) strains has been reported these days.

How big an impact could your results potentially have?
Binding studies of cyanobacterial Cyanovirin-N to mannose-containing moieties are designed.
Broadly neutralizing antiviral agents can be tested for tight binding to viruses based on computational protein design and the number of glycosylation sites involved.

Could you explain the motivation behind this study?
Cyanovirin has been shown to reveal broad neutralizing activity against human immunodeficiency virus (HIV) and to specifically bind Manα(1→2)Manα units exposed on various glycoproteins of enveloped viruses, such as influenza hemagglutinin and Ebola glycoprotein.

In your opinion, what are the key design considerations for your study?
Binding studies of computationally designed binding-site variants of pseudo-antibody Cyanovirin were performed. We show that this protein dimer is cross-linking two carbohydrate binding sites to achieve neutralization ability. It constitutes a domain-swapped naturally stabilized molecule with a single disulfide-bridge linker.

Which part of the work towards this paper proved to be most challenging?
Bound peptides were used as mimicry to a direct complementary binding site of Cyanovirin-N for binding studies. Variants of Cyanovirin-N were mutated to replace native cysteine residues by either charged or nonpolar amino-acids and tested for high-affinity and low-affinity binding to hemagglutinin and mannosylated peptides.

What aspect of your work are you most excited about at the moment?
Finding lectin molecules that allow for the measurement of binding constants to glycoproteins exposed at the surface of immune-stimulating cells.

What is the next step? What work is planned?
The study was pursued by Irene Maier in collaboration with scientists from the University of California, Los Angeles, the Max Perutz Labs, and the University of Vienna, Christian Becker and Philipp Schilling. We aim to investigate the stability of antiviral agents and molecules upon exposure to high-energy and cosmic radiation on Earth and in Space.

We acknowledge the support given by the City of Vienna and the Fulbright U.S. Scholarship Program to I.M.

Mannosylated hemagglutinin peptides bind cyanovirin-N independent of disulfide-bonds in complementary binding sites
Philipp E. Schilling, Georg Kontaxis, Martin Dragosits, Robert H. Schiestl, Christian F. W. Becker and Irene Maier
RSC Adv., 2020,10, 11079-11087
DOI: 10.1039/D0RA01128B, Paper

Submit to RSC Advances today! Check out our author guidelines for information on our article types or find out more about the advantages of publishing in a Royal Society of Chemistry journal.

Keep up to date with our latest HOT articles, Reviews, Collections & more by following us on Twitter. You can also keep informed by signing up to our E-Alerts.