A trustful concentration range was established in which the active agent was effective against the cancer cells but remained non-toxic to the normal cells.
Melanoma is a fast-progressing skin cancer characterized by a high mortality rate after metastasis. Local chemotherapy could be considered a therapeutic approach only in stage 0 of progression (in situ melanoma) and in the postoperative phase after surgical removal of suspected skin lesions. For this purpose, drugs such as Imiquimod, 5-Fluorouracil, Dacarbazine, and Doxorubicin have been tested and shown positive effects. Recently, metal nanoparticles as separate therapeutic units or drug carriers have also fallen into the research focus.
Silver nanoparticles (AgNPs), in particular, are widely recognized as multifunctional tools in nanomedicine, drug delivery, and theranostics. They exert wide-spectrum antimicrobial and anti-tumor properties but their pharmacological effects are in a tight bond with the so-called “surface functionality”. For example, negatively charged and spherical particles are proven less toxic than positively charged particles, especially irregularly shaped (e.g., rods, wires, etc.). Still, because of this, the former are less potent anti-cancer agents.
Contemporary pharmaceutical development relies very much on eco-friendly technologies (often referred to as “green” technologies) that avoid the use of toxic solvents and reagents. This research has implemented one such method based on Camellia sinensis (green tea leaves) as a natural reducer of silver ions. To achieve enhanced antimicrobial and anti-tumor activity, the thus obtained AgNPs were further conjugated to chlorhexidine (Cx+) — a broad-spectrum antimicrobial agent and a cationic surfactant. Indeed, the AgNP-Cx+ complexes have shown highly increased antimicrobial properties, about 18-fold stronger anti-melanoma activity, and 3 times better tumor selectivity compared to the non-functionalized AgNPs.
Anti-tumor activity of silver nanoparticles (AgNPs) and chlorhexidine-silver nanoparticles conjugates (AgNP-Cx+) against melanoma. Legend: ζ-zeta potential – characterizes the charge of the silver nanoparticles; dH hydrodynamic diameter – the size that the particles acquire in an aqueous dispersion; HaCaT – normal cells, human keratinocytes; SH-4 – tumor cells, human melanoma; IC50 – the concentration that inhibits cell proliferation at 50%; SD – standard deviation of the values based on six repetitions of the experiment; ppm – part per million; Selectivity Index – an index that is calculated as the quotient of IC50 on normal cells and IC50 on tumor cells; the greater its value, the more selective the agent against the cancer cells; p-value – statistical indicator; the lower the value the greater the statistical significance between the results obtained with the different samples; a borderline for significance is normally set at p<0.05; n/a – not applicable.
The most valuable outcome of this new study, published in the journal Pharmacia, was the establishment of an adhesive patch prototype as a topical dosage form for the AgNP-Cx+ complex. The used polymers, Hydroxypropyl methylcellulose and Eudragit® RS, demonstrated a lack of negative interference with the antiproliferative action of the active agent but also ensured twice as high activity and even better selectivity against the tumor cells.
Bulgarian Pharmaceutical Scientific Society’s journal join the high-tech ARPHA platform and the fast-expanding portfolio of scholarly titles by Pensoft.Bulgarian Pharmaceutical Scientific Society’s journal join the high-tech ARPHA platform and the fast-expanding portfolio of scholarly titles by Pensoft.
The established Pharmacia demonstrates a complete makeover in its new issue after signing with scientific publisher and technology provider Pensoft and its signature open-access platform
Launched by the Bulgarian Pharmaceutical Scientific Society in 1954, the open-access, peer-reviewed Pharmacia has been available online as full text since 2007. As of 2019, the journal moves to the fast-expanding portfolio of scholarly publisher and technology provider Pensoft. The journal’s 2019 inaugural issue and the first since the realisation of the new partnership is already live on the journal’s new website.
Homepage of Pharmacia‘s new website, https://pharmacia.pensoft.net
Thanks to the Pensoft’s signature open-access scholarly publishing platform ARPHA, Pharmacia demonstrates a complete makeover, including a modern and user-friendly interface in addition to a long list of high-tech perks, meant to ensure that published articles are easy to discover, access, cite and reuse by both humans and machines all over the world.
Furthermore, all users of the journal’s system: authors, editors and reviewers alike, are to greatly benefit of ARPHA’s integrated approach to the publication process. This means that once submitted each manuscript goes through the whole cycle: from review and copy/layout editing to publication, dissemination and archiving without leaving ARPHA’s collaboration-focused online environment.
One of the interesting features now available in Pharmacia is the article-level metrics available thanks to the partnership between ARPHA and the revolutionary discovery and analytics tools Dimensions and Altmetric. By searching through millions of research articles, grant applications, clinical trials, as well as policy documents, news stories, blogs and social media posts, they allow for each article’s references and citations in both the academic and the public sphere to be monitored in real time.
Continuing its tradition, the journal welcomes original research and review articles, preliminary and short communications (notes) on a wide range of topics within the pharmaceutical and related sciences. In addition, the journal also publishes conference reports, biographies and book reviews. Articles in Pharmacia are published in English and subjected to single-blind peer review.
“We have been looking forward to our collaboration with Pensoft and ARPHA, as it is certainly going to not only help modernise Pharmacia on the outside, but also make it more appealing to our authors and readers by building on the journal’s accessibility and global outreach. I believe that this nice step forward is already clearly evident in Pharmacia‘s latest issue.”
ARPHA’s and Pensoft’s founder and CEO Prof Lyubomir Penev says:
“I’m delighted to see this particular journal joining the Pensoft’s and ARPHA’s family,” says ARPHA’s and Pensoft’s founder and CEO Prof. Lyubomir Penev. “With our strong background in scholarly publishing, technology development and open science practices, I am certain that we are able to provide the right venue for a high-quality and enterprising journal like Pharmacia.”
What’s on in the new issue?
The creeping cinquefoil – a perennial plant from the Northern hemisphere – has its status as a traditional medicine for treating diarrhoea, haemorrhoids and bleeding gums confirmed in a collaborative ethnobotanical study by researchers at the Bulgarian Academy of Sciences and the Medical University of Sofia (Bulgaria). Further, the team, led by Irena Mincheva, seek to explore the suggested use of the plant against mastitis: a relatively common disease and a major cause for milk reduction in both people and dairy cows.
Another paper, authored by Dr Illya Podolsky and Sergiy Shtrygol from the National University of Pharmacy in Ukraine, adds new information about “the pharmacological nature” of a molecule already known as a promising antidepressant with a unique spectrum of additional properties. By conducting an experiment in rats, using the preferred Morris water maze assessment method, the scientists study the effects of Atristamine on spatial memory and learning.
Pharmacia‘s latest issue is available on the new website. Available in HTML, XML and PDF formats, the articles are easy to find, access, mine, reuse and cite by both humans and computers. Check out the issue at: https://pharmacia.pensoft.net/issue/1757/.
About the Bulgarian Pharmaceutical Scientific Society:
The Bulgarian Pharmaceutical Scientific Society was registered in 2003 with the aim to organise national and international science forums, support education and publish academic literature. Its main objectives are to organise and encourage pharmacological research and support collaboration between pharmacology professionals and related organisations on both national and global level.
The pharmacological agent outperforms current drugs in most of cases, show multiple experiments
A new pharmacological agent demonstrates promising results for the prevention of a wide range of heart rhythm disorders, including both cardiac and brain injury-induced arrhythmias. Furthermore, the compound (SS-68) demonstrates significant activity in conditions of reduced blood flow to the heart caused by obstructed arteries.
Each year, more than 17 million people from around the globe (mostly Europe and the USA) die of cardiovascular diseases and related complications, according to the World Health Organization. In Russia, about 3 out of 1,000 people suffer from the most common and malignant heart rhythm disorder: atrial fibrillation (AF), where the count is expected to at least double in the next 30 years. While sometimes lacking symptoms, atrial fibrillation could generally be recognised by a racing, irregular heartbeat, dizziness, fatigue, shortness of breath and chest pain, thereby largely compromising the quality of one’s life. The disorder could also lead to various complications, including dementia, stroke and heart failure.
Currently, the drugs administered to AF patients have major deficiencies, including narrow therapeutic windows, which means that even minimal imprecision in the dosage could result in unacceptable toxicity. Hence, patients need to be closely monitored and have their doses adjusted on a regular basis.
In their study, the team turned to the aminoindole derivatives to look for an alternative compound. This chemical group has already shown a significant potential in terms of cardio-pharmacological activity.
Having tested the SS-68 compound on multiple occasions in different animals, the researchers report that it has a pronounced antiarrhythmic effect and is able to bring the electrical activity of the heart back to normal and, in most cases, outperforming the reference drugs used in clinical practice: amiodarone, lidocaine, aymaline, ethacizine, etmozine and quinidine anaprilin.
Further, in brain injury-induced arrhythmias, the compound was found to reduce the episodes of epilepsy. It was also observed to have a positive effect in clogged blood vessels where it is reported to have successfully increased the coronary blood flow. In addition, the compound managed to decrease the area of necrosis in the heart tissue caused by a heart attack.
“To date, there have been significant achievements of Russian and foreign pharmacologists, chemists and clinicians in creating and introducing into the practical medicine a number of antiarrhythmic drugs different by their chemical structure, nature, spectrum, activity and mechanism of action; nevertheless, one of the most important tasks of modern pharmacology is searching for and developing new highly active substances of the corresponding action,” explain the scientists.
“Special attention should be paid to an in-depth study of the molecular mechanisms of action of this compound,” they conclude.
A paper looking further into the molecular mechanisms of the antiarrhythmic action of SS-68 prepared by the same research team is currently in press with Research Results in Pharmacology.
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Original source:
Bogus SK, Galenko-Yaroshevsky PA, Suzdalev KF, Sukoyan GV, Abushkevich VG (2018) 2-phenyl-1-(3-pyrrolidin-1-il-propyl)-1 H-indole hydrochloride (SS-68): Antiarrhythmic and cardioprotective activity and its molecular mechanisms of action (Part I). Research Results in Pharmacology 4(2): 133-150. https://doi.org/10.3897/rrpharmacology.4.2859
