Scientia Pharmaceutica

The main problem in creating anti-coronavirus vaccines that target mainly proteins of the outer membrane of the virus is the rapid variability in the RNA genome of the pathogen that encodes these proteins. In addition, the introduction of technologies that can affordably and quickly produce flexible vaccine formulas that easily adapt to the emergence of new subtypes of SARS-CoV-2 is required. Universal adjuvant oligonucleotide vaccines based on conserved regions of the SARS-CoV-2 genome can take into account the dynamics of rapid changes in the virus genome, as well as be easily synthesized on automatic DNA synthesizers in large quantities in a short time. In this brief report, the effectiveness of four phosphorothioate constructs of the La-S-so-type adjuvant oligonucleotide vaccine is evaluated on B6.Cg-Tg (K18-ACE2)2 transgenic mice for the first time. In our primary trials, the oligonucleotide vaccine increased the survival rate of animals infected with SARS-CoV-2 and also reduced the destructive effects of the virus on the lung tissue of mice, activating both their innate and adaptive immunity. The obtained results show that the development of adjuvant oligonucleotide vaccine constructs of the La-S-so type is an affordable and efficient platform for the prevention of coronavirus infections, including those caused by SARS-CoV-2. Full article

Many medicinal plants found in Africa, such as Dovyallis caffra, have been reported to contain various bioactive compounds, which have been found to reduce metal salts into their corresponding metal-based nanoparticles. In this paper, the evaluation of synthesis, characterization, and biological properties of Dovyallis caffra-mediated cassiterite (SnO₂) nanoparticles was carried out. The physicochemical properties of the synthesized material were investigated using X-ray diffraction (XRD), energy dispersive X-ray analysis (EDX), scanning electron microscopy (SEM), and transmission electron microscopy (TEM) techniques. The characterization studies revealed that the material possessed a single tetragonal cassiterite SnO₂ phase, having a cluster-like foam appearance and an irregular spherical morphology with diameters ranging from 6.57 to 34.03 nm. The biological screening revealed that the prepared cassiterite (SnO₂) nanoparticles exhibited cytotoxicity against the MCF-7 breast cancer cells, with an IC₅₀ value of 62.33 µg mL⁻¹, better than the standard drug 5-fluorouracil, with an IC₅₀ value of 71.21 µg mL⁻¹. The radical scavenging potential of the nanoparticles, using the DPPH assay, showed that it possessed a slightly better activity than ascorbic acid, a common antioxidant. These results suggest that the Dovyallis caffra-mediated cassiterite (SnO₂) nanoparticles possess the potential to simultaneously generate and scavenge excess ROS, which in turn results in the exhibition of good cytotoxicity and antioxidant properties. Full article

In the new antibiotic era, the exponential increase in multiresistant bacterial strains has become the main global health problem. Many researchers have focused their efforts on exploring novel or combined strategies for combating bacterial resistance. Good knowledge of the molecular mechanisms of resistance and bacterial virulence factors as key targets provides us with a good basis for resolving the problem. One particularly attractive and promising strategy is to attack the main regulatory “network” of bacterial virulence determinants known as quorum sensing (QS). The inhibition of QS signals will be a novel means of screening more effective quorum-sensing inhibitors (QSIs) and will play a key role in the use of next-generation antimicrobials in the battle against resistance. This motivated the present review to provide a comprehensive clarification of the regulatory mechanisms of quorum-sensing signaling pathways in Chromobacterium violaceum and the discovery of potential plant quorum-sensing inhibitors. Full article

Cancer is a genetic disorder and its treatment usually requires a long time and expensive diagnosis. While chemotherapy is the most conventional approach in treating most cancers, patients often suffer from undesired side effects due to various pharmacokinetic aspects. To address this issue, target-oriented drug-delivery systems (DDS) or pulsatile drug-delivery systems (PDDS) have recently been developed as an alternative tool that takes care of the entire pharmacodynamic activities of drug action. Hydroxyethyl starch (HES) has emerged as an effective clinical tool for delivering anticancer agents into target cells. These systems have demonstrated significant potential as anticancer drug carrier conjugates through their innate pharmacokinetic properties with their safety profile. This review focuses primarily on the structural aspect during the use of HES or HES-based polymers as carriers for delivering well-known anticancer drugs. This review also indicates a perspective on the long-term research needed for the sake of improving modern drug-delivery systems based on HES polymers and in the form of nanocarriers. Full article

Alterations in the biological activity of the molecules under stress conditions have not been documented as widely in the literature yet. This study was designed to reveal the functional impacts of various oxidation conditions on a model mAb, a commercial anti-VEGF IgG molecule. The responses to antigen binding, cell proliferation, FcRn receptors, and C1q binding, which rarely appear in the current literature, were investigated. The authors report peptide mapping data, post-translational modification (PTM) analysis, cell proliferation performance, and antigen (VEGF), C1q, and FcRn binding activities of the mAb under various stress conditions. The oxidation-prone site of the mAb was determined as Met252 in the DTLMISR peptide. The VEGF binding activity and anti-cell proliferation activity of the mAbs did not alter, while C1q and FcRn binding capacity significantly decreased under oxidative stress conditions. The full report is vital for many scientific and industrial processes about mAbs. The authors recommend performing functional analyses in addition to the structural studies while investigating the impacts of stress factors on therapeutic mAbs. Full article

This study aimed to prepare tablets of black pepper extract using the Design of Experiments (DOE) approach. The levels of three factors—compressional force, croscarmellose sodium (CCS), and microcrystalline cellulose (MCC)—were screened using the one-factor-at-a-time technique, followed by the DOE utilizing the Box–Behnken design. The respective variations for each factor were as follows: compressional force (1500–2500 psi), CCS (1–3%), and MCC (32–42%). The results indicated that compressional force significantly decreased tablet thickness and friability, while increasing hardness and prolonging disintegration time. CCS significantly shortened disintegration time but did not affect tablet thickness, hardness, and friability. MCC, on the other hand, significantly increased tablet thickness and hardness, while significantly decreasing friability. Furthermore, the study observed interactions among factors and quadratic effects of each factor, which significantly influenced tablet properties. The optimal tablet formulation consisted of 2.2% CCS, 37% MCC, and a compressional force of 2000 psi. These tablets had a weight of 198.39 ± 0.49 mg, a diameter of 9.67 ± 0.01 mm, a thickness of 1.98 ± 0.02 mm, a hardness of 7.36 ± 0.24 kP, a friability of 0.11 ± 0.02%, and a disintegration time of 5.59 ± 0.39 min. The actual values obtained using the optimal conditions closely matched the predicted values, with a low percent error (less than 5%). In conclusion, the application of the DOE approach successfully developed tablets of black pepper extract, which can be utilized as food supplement products. Full article

The actions of Eli Lilly-rDNA glucagon and Novo Nordisk-rDNA glucagon on glycogen catabolism and related parameters were investigated using the bivascularly perfused rat liver. The technique allows glucagon to be supplied to a selective portion of the hepatic periportal region (≈39%) when the former is infused into the hepatic artery in retrograde perfusion. Both glucagon preparations were equally effective in influencing metabolism (glucose output, glycolysis and O₂ uptake) when supplied to all cells along the liver sinusoids. When only a selective periportal region of the liver was supplied with the hormone, however, the action of Novo Nordisk-rDNA glucagon was proportional to the accessible cell space, whereas the action of Eli Lilly-rDNA glucagon greatly exceeded the action that was expected for the accessible space. Chromatographically, both rDNA preparations were not pure, but their impurities were not the same. The impurities in Eli Lilly-rDNA glucagon resembled those found in the similarly acting pancreatic Eli Lilly glucagon. It was concluded that the space-extrapolating action of Eli Lilly-rDNA glucagon is caused by a yet-to-be-identified impurity. The hypothesis was raised that an impurity in certain glucagon preparations can enhance cell-to-cell propagation of the glucagon signal, possibly via gap junctional communication. Full article

The modern world, swaddled in the benefits of civilization, has fostered the development of science and the introduction of products of technological progress. This has allowed serious individual health problems, including those associated with viral diseases, to become targets for prophylaxis, treatment, and even cure. Human immunodeficiency viruses, hepatitis viruses, coronaviruses, and influenza viruses are among the most disturbing infectious agents in the human experience. Influenza appears to be one of the oldest viruses known to man; these viruses were among the first to cause major epidemics and pandemics in human history, collectively causing up to 0.5 million deaths worldwide each year. The main problem in the fight against influenza viruses is that they mutate constantly, which leads to molecular changes in antigens, including outer membrane glycoproteins, which play a critical role in the creation of modern vaccines. Due to the constant microevolution of the virus, influenza vaccine formulas have to be reviewed and improved every year. Today, flu vaccines represent an eternal molecular race between a person and a virus, which neither entity seems likely to win. Full article

Microneedles are gaining popularity as a new paradigm in the area of transdermal drug delivery for biomedical and healthcare applications. Efficient drug delivery with minimal invasion is the prime advantage of microneedles. The concept of the microneedle array provides an extensive surface area for efficient drug delivery. Various types of inorganics (silicon, ceramic, metal, etc.) and polymeric materials are used for the fabrication of microneedles. The polymeric microneedles have various advantages over other microneedles fabricated using inorganic material, such as biocompatibility, biodegradation, and non-toxicity. The wide variety of polymers used in microneedle fabrication can provide a broad scope for drug delivery and other biomedical applications. Multiple metallic and polymeric microneedles can be functionalized by polymer coatings for various biomedical applications. The fabrication of polymeric microneedles is shifting from conventional to advanced 3D and 4D printing technology. The multifaceted biomedical applications of polymeric microneedles include drug delivery, vaccine delivery, biosensing, and diagnostic applications. Here, we provide the overview of the current and advanced information on polymers used for fabrication, the selection criteria for polymers, biomedical applications, and the regulatory perspective of polymer-based and polymer-coated microneedles, along with a patent scenario. Full article

Non-steroidal anti-inflammatory drugs (NSAIDs) are one of the oldest and most widely used groups of drugs nowadays. However, the problem of searching for and creating new NSAIDs remains open, primarily due to the risks owing to their short- and long-term use. In this context, triazole-azepine hybrid molecules are attractive and prospective objects for the rational design of novel potential NSAIDs. In the present work studies of 3-aryl-6,7,8,9-tetrahydro-5H-[1,2,4]triazolo[4,3-a]azepines as potential non-steroidal anti-inflammatory agents are reported. Evaluation of drug-like properties for all tested triazole-azepine hybrids was performed in silico using SwissADME. The screening of analgesic and anti-inflammatory activities was performed in vivo using acid-induced writhing and carrageenin-induced hind paw oedema models in mice. Derivatives with activity levels more potent compared with reference drugs ketorolac and diclofenac sodium were identified. Preliminary SAR was performed based on the screening results. Full article

Etifoxine is an anxiolytic drug with a dual mechanism of action. In contrast to conventional benzodiazepine anxiolytics, which induce cognitive dysfunction and myorelaxation, no memory impairment nor a decrease in motor activity is observed with etifoxine. This study aims to evaluate the effects of etifoxine on locomotor activity and passive learning in rats with diazepam-induced memory deficit. Male Wistar rats were treated intraperitoneally for 7 days with: (1) saline; (2) diazepam 2.5 mg/kg bw or (3) diazepam 2.5 mg/kg bw and etifoxine in a dose of 50 mg/kg bw. Activity cage test was used for evaluation of locomotor activity, and step-through and step-down tests were performed to study the passive learning. Etifoxine increased the number of horizontal movements on the 7th and 14th days of the experiment. The drug exhibits anti-amnesic effect in a model of diazepam-induced anterograde amnesia by enhancing long-term memory in passive learning tests. The data obtained suggest that etifoxine can reduce the benzodiazepine-induced cognitive deficit. Moreover, such a combination can alleviate the negative influence of benzodiazepines on locomotor activity. However, additional studies are necessary to translate these results into clinical practice. Full article

The Zingiber montanum herbal compress remedy is a type of herbal medicine that can be used as an alternative treatment for improving pain symptoms. This study aimed to evaluate the clinical efficacy of a Z. montanum herbal compress remedy for pain relief. PubMed, Scopus, ScienceDirect, and Thai databases were systematically searched for relevant articles published from inception to December 2022. Only randomized clinical trials (RCTs) wherein the efficacy of the Z. montanum remedy was compared to that of a placebo or non-steroidal anti-inflammatory drugs (NSAIDs) were included. Six RCTs with a total of 812 patients were included in the analysis. The efficacy of the Z. montanum remedy had a significantly decreased pain score compared to the placebo (SMD = −0.63; 95% CI = −1.20, −0.06; I² = 90%), but there was no significant difference when compared to NSAIDs (SMD = −0.61; 95% CI = −1.41, 0.81; I² = 73%). Moreover, the efficacy of the Z. montanum remedy in terms of the flexibility score (SMD = 0.59; 95% CI −0.56, 1.74; I² = 86.0%) and quality of life (SMD = 0.34; 95% CI −0.38, 1.05; I² = 81.0%) was similar to that of the placebo. This meta-analysis demonstrates that the use of the Z. montanum herbal compress remedy significantly reduces the pain scores reported by patients. Full article

The aim of this study is to compare three different dissolution methods to assess the drug release from oral lyophilisates, based on interpolyelectrolyte complexes (IPECs). IPECs were prepared by mixing solutions of a linear polymer, Eudragit^® EPO, with a polymer with a cross-linked structure, Noveon^® AA-1 or Carbopol^® 10 Ultrez (in ratios of 1:2 and 1:1, respectively). Metformin or metronidazole were used as model drugs to achieve a systemic or local effect. A comparative assessment of the drug release kinetics was carried out using artificial saliva and three different set-ups: a paddle stirrer (USP apparatus 2), a flow cell (USP apparatus 4) and a Franz diffusion cell. The results demonstrated that oral lyophilisates disintegrated within 1 min. In the case of metformin, the drug release was completed in about 90 min independently of the set-up. The static conditions in the Franz diffusion cell and USP apparatus 2 permitted the aggregation of the IPEC; therefore, the release profiles show a significant difference compared to the USP apparatus 4. Full article

Yerba-mate contains in its composition a high concentration of phenolic compounds. This class of secondary metabolites exhibits strong values of molar absorptivity on ultraviolet and visible wavelengths. This study evaluated the effect of yerba-mate extracts on the in vitro solar protection factor (SPF) value of sunscreen formulations. The sunscreen formulations were prepared to have non-ionic lotion as a basis and yerba-mate extract and/or avobenzone as active agents. The SPF and resveratrol protective effect of the formulations were determined by UV-vis spectrometry. A synergic effect between the yerba-mate extract and avobenzone on the SPF was found. Yerba-mate extract at 5% improved the SPF of the avobenzone 5% formulation from 28.46 ± 5.45 to 40.48 ± 0.84. Yerba-mate extract at 5% avoided resveratrol degradation by ultraviolet radiation. At this same concentration, avobenzone produced a smaller effect than yerba-mate extracts in resveratrol protection. The formulations with yerba-mate + avobenzone presented smaller changes in pH values during 12 days of storage. The spreadability profile of yerba-mate and avobenzone formulations was similar to the profile of avobenzone formulations. The results reported here show the suitability of the yerba-mate extract use in photoprotective formulations, highlighting their in vitro effect and opening possibilities for new investigations exploring this property. Full article

Our main target was to develop methods for the quality control of the tablet «ramipril» according to the indicators of «Quantitative determination», «Impurities» and «Dissolution». New, precise, accurate and green HPLC methods were developed for the determination of ramipril and its impurities in tablets. The separation was accomplished using a diode array detector at 210 nm with an isocratic and gradient mobile phase consisting of a 0.2 g/L solution of sodium hexanesulfonate (pH 2.7) and the acetonitrile and chromatographic columns Acclaim 120 C18 and Inertsil ODS-3. The developed method was validated in accordance with ICH guidelines. The analysis of impurities was performed within a run duration of less than 25 min, which is about a two times shorter than that of the official Ph. Eur. method. The analysis of ramipril in tablets was performed with a run duration of less than 4.5 min, which is about three times shorter than that of the official USP method. The developed methods were successfully applied for the quality control of the tablet «ramipril» according to the indicators of «Quantitative determination», «Impurities» and «Dissolution». In addition, they proved its superiority over the reported methods in terms of greenness using different assessment tools. Full article

Skin inflammation occurs as an immune response to various stimuli such as ultraviolet light, irritants, or any type of skin barrier injury. Finding safe and effective drugs to combat skin inflammation remains a research challenge. Ethical and legal considerations in animal testing encourage the development of in vitro and ex vivo models for the detection of skin inflammation. This report presents an updated review of non-animal study models available for screening drugs with anti-inflammatory potential. It includes a description of the basic methods used to inhibit protein denaturation and red blood cell membrane stability. Three in vitro inhibition assay methods for enzymes relevant to the skin inflammatory process are then described. The development of cell culture models is described: relatively simple and easy-to-produce two-dimensional (2D) skin cell cultures that allow assessment of response to a given stimulus, three-dimensional (3D) cell cultures that better mimic human skin physiology by more accurately replicating mechanical and chemical signals, and vascularized 3D skin models with dynamic perfusion and microfluidic devices known as skin on a chip. Finally, ex vivo skin models are presented that could more accurately represent human skin in terms of structure, cell signaling mechanisms, and absorption effects. Although the current development of models without the use of animals is promising, improvements and refinements are needed to make the models more suitable as screening platforms for topical anti-inflammatory drugs. Full article

Carnosol is a natural diterpene present in Rosmarinus officinalis L. (rosemary) with anti-tumor and anti-inflammatory properties. Despite its importance, the pharmacological mechanisms underlying the interactions between carnosol and human targets are still unclear. The goal was to identify plausible human target for carnosol and the network pharmacology. Rosemary was analyzed using HPLC-QTOF-MS/MS. Potential carnosol targets were identified using docking and a public database (CTD). Carnosol was screened against 708 human proteins using AutoDock Vina, and affinity values were used as prioritization criteria. The targets set was uploaded to WebGestalt to obtain Gene Ontology (GO) and KEGG pathway enrichment analysis. HPLC-QTOF-MS/MS analyses allowed the tentative annotation of nine chemicals, with carnosol being the most ionized. There were 53 plausible targets for carnosol, with 20 identified using virtual screening, including Hsp90α (−10.9 kcal/mol), AKR1C3 (−10.4 kcal/mol), and Hsp90β (−10.4 kcal/mol), and 33 identified from CTD. The potential targets for carnosol identified with PPI and molecular docking were HSP90AA1, MAPK1, MAPK3, CAT, JUN, AHR, and CASP3. GO terms and KEGG pathways analysis found that carnosol is closely related to infection (Chagas, influenza A, toxoplasmosis, and pertussis) and inflammation (IL-17 and TNF signaling pathway and Th-17 cell differentiation). These results demonstrated that carnosol may induce an immuno-inflammatory response. Full article

Cancer is a large group of diseases that can affect any organ or body tissue due to the abnormal cellular growth with the unknown reasons. Many of the existing chemotherapeutic agents are highly toxic with a low level of selectivity. Additionally, they lead to development of therapeutic resistance. Hence, the development of targeted chemotherapeutic agents with low side effects and high selectivity is required for cancer treatment. Quinazoline is a vital scaffold well-known to be linked with several biological activities. The anticancer activity is one of the prominent biological activities of this scaffold. Several established anticancer quinazolines work by different mechanisms on the various molecular targets. The aim of this review is to present different features of medicinal chemistry as drug design, structure activity relationship, and mode of action of some targeted anticancer quinazoline derivatives. It gives comprehensive attention on the chemotherapeutic activity of quinazolines in the viewpoint of drug discovery and its development. This review provides panoramic view to the medicinal chemists for supporting their efforts to design and synthesize novel quinazolines as targeted chemotherapeutic agents. Full article

This research sought to optimize the microwave-assisted extraction of Chatuphalathika as an herbal recipe maximizing the active compounds and the antioxidant activity by the Box–Behnken design. Three factors—microwave power, time, and cycle—were varied. Eight responses—extraction yield, total phenolic content, gallic acid content, corilagin content, chebulagic acid, chebulinic acid, IC₅₀ from DPPH assay, and IC₅₀ from FRAP assay—were monitored. Furthermore, cytotoxicity was evaluated to ensure the safety of the extract. After that, the optimized extract was compressed into tablets. The results showed that the optimal condition of the microwave-assisted extraction gave the simultaneous maximum extraction yield, total phenolic content, and antioxidant activity with a microwave power of 450 W for 30 s and 3 cycles. The extract obtained from the optimal condition exhibited a good safety profile although a concentration of 5 mg/mL was used. The optimized tablets were achieved when a compression force of 1500 psi and magnesium stearate of 1% were applied, and no sodium starch glycolate was added. In conclusion, the optimal green extraction method could be used for the extraction of the Chatuphalathika. Furthermore, the fabrication of Chatuphalathika tablets was successful, as the tablets had low friability with a short disintegration time. Full article