Scientia Pharmaceutica

20 pages, 3501 KiB

Open AccessArticle

Development of a Comprehensive Approach to Quality Control of Dermorphin Derivative—Representative of Synthetic Opioid Peptides with Non-Narcotic Type of Analgesia

by Vasilisa A. Sukhanova, Elena V. Uspenskaya, Safdari Ainaz, Hoang Thi Ngoc Quynh and Aleksey A. Timofeev

Sci. Pharm. 2025, 93(1), 3; https://doi.org/10.3390/scipharm93010003 - 31 Dec 2024

Abstract

Peptides occupy a significant share of the pharmaceutical market and are among the top-200 selling drugs in the group of non-insulin drugs with analgesic, antibacterial and cardiovascular effects. The aim of this work is to develop a comprehensive analytical approach for quality control [...] Read more.

Peptides occupy a significant share of the pharmaceutical market and are among the top-200 selling drugs in the group of non-insulin drugs with analgesic, antibacterial and cardiovascular effects. The aim of this work is to develop a comprehensive analytical approach for quality control of novel synthetic peptides with non-narcotic types of analgesia and to provide docking simulations of dermorphin complex formation at the μ-opioid receptor (MOR) binding site. The materials and methods used include the pharmaceutical substance dermorphin tetrapeptide (DMTP) (tyrosyl-D-arginyl-phenylalanyl-glycinamide); Fourier transform infrared spectroscopy (FT-IR); static and dynamic laser light scattering (DLS, LALLS); scanning optical microscopy (SEM); X-ray fluorescence elements analysis; polarimetry for optical activity determining; and Spirotox method for sample biotesting. FT-IR-Spectra indicated specific amino acid chemical groups in the tetrapeptide sequence at 3300–2700 cm⁻¹, 1670 cm⁻¹. UV-absorption spectra of aqueous solutions of dermorphin tetrapeptide showed an absorption maximum at 275 nm, which is in good agreement with the presented spectrum of the bovine serum albumin (BSA) standard; the Pearson’s r of calibration line “A-C%” in 0.0125% to 0.0500% concentration range is 0.999; and the calculated specific extinction value

E_{1 c m}^{1 %}

= 18.38 ± 0.23. Of the 11 elements detected by X-rays, the elements copper (Cu) and cobalt (Co) have the highest X-ray intensity. Dispersion characteristics of dermorphin solutions were studied in the submicron and micron range. Conglomerates and druzes were detected by SEM, ranging in size from 2 µm to 100 µm. The specific optical activity index was calculated

{[α]}_{D}^{20}

= +36.18 ± 2.04 [°·mL·g⁻¹·dm⁻¹], according to Biot’s Law. Additionally, the orientation and conformation of the dermorphin molecule in the active binding site of the 8E0G receptor were predicted using molecular modeling, revealing that the contact area affects the key amino acid residue arginine (ARG 182). This comprehensive approach to analytical methods for qualitative and quantitative analysis of dermorphin tetrapeptide can be applied in pharmacies to enhance the understanding of its biological activity and aid in the development of regulatory documentation for a new, non-narcotic analgesic based on the dermorphin tetrapeptide. Full article

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21 pages, 6841 KiB

Open AccessArticle

Marine Origin vs. Synthesized Compounds: In Silico Screening for a Potential Drug Against SARS-CoV-2

by Amar Osmanović, Mirsada Salihović, Elma Veljović, Lamija Hindija, Mirha Pazalja, Maja Malenica, Aida Selmanagić and Selma Špirtović-Halilović

Sci. Pharm. 2025, 93(1), 2; https://doi.org/10.3390/scipharm93010002 - 26 Dec 2024

Abstract

Although COVID-19 is not a pandemic anymore, the virus frequently mutates, resulting in new strains and presenting global public health challenges. The lack of oral antiviral drugs makes it difficult to treat him, which makes the creation of broadly acting antivirals necessary to [...] Read more.

Although COVID-19 is not a pandemic anymore, the virus frequently mutates, resulting in new strains and presenting global public health challenges. The lack of oral antiviral drugs makes it difficult to treat him, which makes the creation of broadly acting antivirals necessary to fight current and next epidemics of viruses. Using the molecular docking approach, 118 compounds derived from marine organisms and 92 previously synthesized compounds were screened to assess their binding affinity for the main protease and papain-like protease enzymes of SARS-CoV-2. The best candidates from the xanthene, benzoxazole, and coumarin classes were identified. Marine-derived compounds showed slightly better potential as enzyme inhibitors, though the binding affinities of synthesized compounds were similar, with the best candidates displaying affinity values between 0.2 and 0.4 mM. Xanthenes, among both marine origin and synthesized compounds, emerged as the most promising scaffolds for further research as inhibitors. The papain-like protease was found to be more druggable than the main protease. Additionally, all top candidates met the criteria for various drug-likeness properties, indicating good oral bioavailability and low risk of adverse effects. This research provides valuable insights into the comparative affinities of marine origin and synthesized compounds from the xanthene, coumarin, and benzoxazole classes, highlighting promising candidates for further in vitro and in vivo studies. Full article

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26 pages, 5193 KiB

Open AccessReview

Colon Cancer: Overview on Improved Therapeutic Potential of Plant-Based Compounds Using Nanotechnology

by Manuel López-Cabanillas Lomelí, Alexandra Tijerina-Sáenz, David Gilberto García-Hernández, Marcelo Hernández-Salazar, Rogelio Salas García, José Luis González-Llerena, María Julia Verde-Star, Anthonny Cordero-Díaz and Michel Stéphane Heya

Sci. Pharm. 2025, 93(1), 1; https://doi.org/10.3390/scipharm93010001 - 24 Dec 2024

Abstract

Colon cancer (CC) is the third most frequent neoplasm, with a considerably high mortality rate. Due to the side effects of conventional forms of CC treatment (surgery, chemotherapy, and radiotherapy), several studies have focused on the use of medicinal plant derivatives to provide [...] Read more.

Colon cancer (CC) is the third most frequent neoplasm, with a considerably high mortality rate. Due to the side effects of conventional forms of CC treatment (surgery, chemotherapy, and radiotherapy), several studies have focused on the use of medicinal plant derivatives to provide a green therapy for CC; although phytochemicals have shown promising results against CC, translating the results obtained in vitro and in vivo to the clinical setting remains a challenge. Indeed, like other orally applied medicines, medicinal plant derivatives have to cross different physiological barriers to reach the CC microenvironment, which considerably limits their dose-dependent therapeutic efficacy. On the other hand, phytocompounds are not free from biopharmaceutical drawbacks, so novel strategies using nanoparticles (NPs) have been proposed to overcome the physiological barriers of the body and provide controlled release of actives of interest. Accordingly, the current review provides an overview and discussion on the predisposing factors to CC and conventional treatment, the use of medicinal plants in CC treatment, and the advantages provided by NPs in the treatment of CC. Full article

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18 pages, 4289 KiB

Open AccessArticle

Antidiabetic Effect of Dihydrobetulonic Acid Derivatives as Pparα/γ Agonists

by Mikhail V. Khvostov, Mikhail E. Blokhin, Sergey A. Borisov, Vladislav V. Fomenko, Yulia V. Meshkova, Natalia A. Zhukova, Sophia V. Nikonova, Sophia V. Pavlova, Maria A. Pogosova, Sergey P. Medvedev, Olga A. Luzina and Nariman F. Salakhutdinov

Sci. Pharm. 2024, 92(4), 65; https://doi.org/10.3390/scipharm92040065 - 5 Dec 2024

Abstract

Dual PPARα/γ agonists can normalize both glucose and lipid metabolism in patients with type 2 diabetes mellitus. The development of such drugs faced the detection of various toxic effects in phase III clinical trials. However, two drugs of this class managed to pass [...] Read more.

Dual PPARα/γ agonists can normalize both glucose and lipid metabolism in patients with type 2 diabetes mellitus. The development of such drugs faced the detection of various toxic effects in phase III clinical trials. However, two drugs of this class managed to pass all stages of clinical trials, which makes the search for new dual PPARα/γ agonists promising. In the present study, a series of dihydrobetulonic acid amides differing in the length of the amino-alcohol linker and incorporating a pharmacophore fragment of (S)-2-ethoxy-3-phenylpropanoic acid were synthesized. The in vitro study showed that the length of the aminoalcohol linker dramatically affects the level of activation of PPAR-α and γ receptors. The synthesized compounds were tested for their ability to improve glycemic control and to counter lipid abnormalities in C57Bl/6 Ay/a mice at a dose of 30 mg/kg. Of all the compounds tested, the dihydrobetulonic acid derivative with an aminoethanol linker (15a) had the most pronounced effect in improving insulin sensitivity and glucose tolerance, and in reducing blood triglyceride levels. In addition, 15a dramatically counteracted the pathological changes in the liver, pancreas, kidney, and brown fat tissue that are characteristic of type 2 diabetes. Full article

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19 pages, 2052 KiB

Open AccessArticle

Model Adequacy in Assessing the Predictive Performance of Regression Models in Pharmaceutical Product Optimization: The Bedaquiline Solid Lipid Nanoparticle Example

by Chidi U. Uche, Mercy A. Okezue, Ibrahim Amidu and Stephen R. Byrn

Sci. Pharm. 2024, 92(4), 64; https://doi.org/10.3390/scipharm92040064 - 4 Dec 2024

Abstract

This study aimed to assess the predictive performance of first- and second-order regression models in optimizing bedaquiline (BQ) solid lipid nanoparticle (SLN) formulations. A three-step central composite design and graphical optimization process was employed. A design of experiments method was used to evaluate [...] Read more.

This study aimed to assess the predictive performance of first- and second-order regression models in optimizing bedaquiline (BQ) solid lipid nanoparticle (SLN) formulations. A three-step central composite design and graphical optimization process was employed. A design of experiments method was used to evaluate the impact of BQ, Tween 80 (T80), polyethylene glycol (PEG), and lecithin on the formulations’ response variables, including Z-average (PSD), polydispersibility index (PdI), and Zeta potential (ZP). Secondly, we quantified the relationship between experimental variables using the regression model coefficients. Lastly, we predicted the responses and verified the models’ adequacies to ensure accurate representation and effective optimization. The first-order polynomial showed poor model adequacy and required further refinement due to its lack of explanatory power and significant predictors. Conversely, the second-order models provided superior fitness, sensitivity to variability, complexity, and prediction consistency. The optimized formulation achieved a desirability value of 0.9998, indicating alignment with the desired criteria. Specifically, the levels of BQ (19.4 mg), T80 (25.2 mg), PEG (39.2 mg), and lecithin (200 mg) corresponded to PdI (0.41), PSD (250.99 nm), and ZP (−25.95 mV). Maintaining a BQ concentration between 10 and 20% and T80 between 15 and 18% is vital for maximizing ZP and minimizing PdI and PSD, ensuring stable SLN formulations. This study underscores the significance of precise model selection and statistical analysis in pharmaceutical formulation optimization for enhanced drug delivery systems. Full article

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19 pages, 7948 KiB

Open AccessArticle

New Approaches to Determining the D/H Ratio in Aqueous Media Based on Diffuse Laser Light Scattering for Promising Application in Deuterium-Depleted Water Analysis in Antitumor Therapy

by Anton V. Syroeshkin, Elena V. Uspenskaya, Olga V. Levitskaya, Ekaterina S. Kuzmina, Ilaha V. Kazimova, Hoang Thi Ngoc Quynh and Tatiana V. Pleteneva

Sci. Pharm. 2024, 92(4), 63; https://doi.org/10.3390/scipharm92040063 - 2 Dec 2024

Abstract

The development of affordable and reliable methods for quantitative determination of stable atomic nuclei in aqueous solutions and adjuvant agents used in tumor chemotherapy is an important task in modern pharmaceutical chemistry. This work quantified the deuterium/prothium isotope ratio in aqueous solutions through [...] Read more.

The development of affordable and reliable methods for quantitative determination of stable atomic nuclei in aqueous solutions and adjuvant agents used in tumor chemotherapy is an important task in modern pharmaceutical chemistry. This work quantified the deuterium/prothium isotope ratio in aqueous solutions through an original two-dimensional diffuse laser scattering (2D-DLS) software and hardware system based on chemometric processing of discrete interference patterns (dynamic speckle patterns). For this purpose, 10 mathematical descriptors (d_i), similar to QSAR descriptors, were used. Correlation analysis of bivariate “log d_i—D/H” plots shows an individual set of multi-descriptors for a given sample with a given D/H ratio (ppm). A diagnostic sign (DS) of differentiation was established: the samples were considered homeomorphic if 6 out of 10 descriptors differed by less than 15% (n ≥ 180). The analytical range (r = 0.987) between the upper (D/H ≤ 2 ppm) and lower (D/H = 180 ppm) limits for the quantification of stable hydrogen nuclei in water and aqueous solutions were established. Using the Spirotox method, a «safe zone» for protozoan survival was determined between 50 and 130 ppm D/H. Here, we discuss the dispersive (DLS, LALLS) and optical properties (refractive index, optical rotation angle) of the solutions with different D/H ratios that define the diffuse laser radiation due to surface density inhomogeneities. The obtained findings may pave the way for the future use of a portable, in situ diffuse laser light scattering instrument to determine deuterium in water and aqueous adjuvants. Full article

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9 pages, 965 KiB

Open AccessArticle

Avelumab in First Line Maintenance in Advanced Urothelial Carcinoma (aUC) in Elderly Patients: Efficacy, Tolerability, and Quality of Life in Real Life Setting

by Rossella De Luca, Pasquale Vitale, Alessio Pepe, Roberta Spedaliere, Alchiede Simonato, Raffaele Addeo and Giuseppe Cicero

Sci. Pharm. 2024, 92(4), 62; https://doi.org/10.3390/scipharm92040062 - 28 Nov 2024

Abstract

(1) Background Immune checkpoint inhibitors (ICIs) have recently become an important therapeutic option for patients with advanced urothelial carcinoma (aUC). Avelumab is an anti-PD-L1 (programmed cell death ligand 1) antibody that restores antitumor T-cell immune function by blocking the binding of PD-1 to [...] Read more.

(1) Background Immune checkpoint inhibitors (ICIs) have recently become an important therapeutic option for patients with advanced urothelial carcinoma (aUC). Avelumab is an anti-PD-L1 (programmed cell death ligand 1) antibody that restores antitumor T-cell immune function by blocking the binding of PD-1 to its ligand PD-L1. (2) Methods: Our study enrolled 60 elderly patients (≥70 years) diagnosed with aUC. The primary endpoints of this study were overall survival (OS), progression free survival (PFS), and objective response rate (ORR); the secondary endpoints were tolerability, pre- and post- treatment reduction in serum Ca 19.9, and quality of life (QoL). (3) Results: Our results showed no statistically significant or clinically relevant differences between the PD-L1-positive and negative groups. Avelumab was well tolerated and resulted in good disease control, with a moderate toxicity profile and significant clinical benefit. The median PFS was 3.6 months (95% CI: 2.3–6.8), and the median OS was 18.6 months (95% CI: 6.3–20.7), with an ORR of 20%. A significant correlation was observed between serum Ca 19.9 reduction and PFS of 0.59 (95% CI: 0.12–0.57), p = 0.007. (4) Conclusions: Avelumab is an immunotherapy treatment that has been shown to be an effective and well tolerated treatment option in elderly patients with aUC. Full article

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11 pages, 469 KiB

Open AccessReview

Corticosteroids and the Pharmacological Management of Autism—An Integrative Review

by Lillian Amanda Gabarrão de Jesus, Grasiela Piuvezam, Isac Davidson Santiago Fernandes Pimenta and Eduardo Borges de Melo

Sci. Pharm. 2024, 92(4), 61; https://doi.org/10.3390/scipharm92040061 - 22 Nov 2024

Abstract

Autism spectrum disorder (ASD), or autism, is a lifelong neurodevelopmental condition typically detected during early childhood, for which no specific and efficient pharmacological management is currently available. No drugs have been developed specifically for the pharmacological management of autism. Thus, this approach often [...] Read more.

Autism spectrum disorder (ASD), or autism, is a lifelong neurodevelopmental condition typically detected during early childhood, for which no specific and efficient pharmacological management is currently available. No drugs have been developed specifically for the pharmacological management of autism. Thus, this approach often relies on various conventional psychotropic medications and, depending on the condition, other medications may also be used. Some studies available in the literature indicate that the adjunctive use of corticosteroids can help improve the quality of life of individuals with autism. Therefore, we conducted an integrative review using four databases, which were PubMed, Scopus, Web of Science, and Google Scholar, focusing on clinical trials and animal model studies involving corticosteroids related to autism. We analyzed the effects of treatment on core and associated autism symptoms, as well as adverse effects. Eight studies were selected and analyzed, seven involving humans and one using an animal model. These studies focused on the drugs pregnenolone (3), prednisolone (3), hydrocortisone (1), and betamethasone (1) in trials either alone or in combination with other medications (such as risperidone). We observed that corticosteroids safely and effectively reduced several symptoms, including stereotypical and social behaviors, hyperactivity, and irritability. Furthermore, no serious adverse effects were observed, although all selected studies were of short duration. Thus, corticosteroids are promising options to be included in the pharmacological management of autism, whether or not in combination with other medications, and further studies are needed to evaluate their long-term effectiveness. Full article

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12 pages, 4647 KiB

Open AccessArticle

The Effect of Insulin-like Growth Factor-1 on the Quantitative and Qualitative Composition of Phosphoinositide Cycle Components During the Damage and Regeneration of Somatic Nerves

by Marina Parchaykina, Elena Chudaikina, Elvira Revina, Ivan Molchanov, Anastasia Zavarykina, Egor Popkov and Victor Revin

Sci. Pharm. 2024, 92(4), 60; https://doi.org/10.3390/scipharm92040060 - 14 Nov 2024

Abstract

One of the pressing issues in regenerative medicine is the restoration of somatic nerve function after injury. In this study, extraction methods were used to obtain lipids from nervous tissue, followed by chromatographic separation, quantitative analysis via densitometry, and qualitative and quantitative analyses [...] Read more.

One of the pressing issues in regenerative medicine is the restoration of somatic nerve function after injury. In this study, extraction methods were used to obtain lipids from nervous tissue, followed by chromatographic separation, quantitative analysis via densitometry, and qualitative and quantitative analyses of the fatty acid composition through gas chromatography. The results showed that nerve cutting results in the accumulation of all forms of phosphoinositides and a decrease in diacylglycerol (DAG) levels in both the proximal and distal segments of the nerve conductor. This phenomenon is likely attributable to the inactivation of phosphoinositide-specific phospholipase C and the activation of lipolytic enzymes, particularly phospholipases A₁ and A₂, resulting in an increase in the amount of free fatty acids (FFAs). The intramuscular administration of insulin-like growth factor-1 (IGF-1) was associated with enhanced phosphoinositide metabolism, increased DAG levels, reduced FFA levels, and a redistribution of fatty acids within the studied lipid fractions. The registration method of action potentials demonstrated the restoration of nerve conduction in the proximal segment of somatic nerves following the introduction of IGF-1. This correlates with our findings regarding alterations in the lipid fraction composition of damaged nerve conductors in response to the drug’s effects. Most likely, IGF-1 exerts its effects through activation of the phosphoinositide-specific phospholipase C and phosphatidylinositol-3 kinase signaling pathways, which are necessary for axonal regeneration and the restoration of functioning damaged nerve conductors. Full article

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14 pages, 808 KiB

Open AccessReview

Resveratrol: Extraction Techniques, Bioactivity, and Therapeutic Potential in Ocular Diseases

by Giulia Accomasso, Flavia Turku, Simona Sapino, Daniela Chirio, Elena Peira and Marina Gallarate

Sci. Pharm. 2024, 92(4), 59; https://doi.org/10.3390/scipharm92040059 - 14 Nov 2024

Abstract

Resveratrol (RV), a natural polyphenol found in various plants, exhibits a wide range of bioactive properties and mechanisms of action. Its potential therapeutic benefits in several diseases and, more specifically, in ocular diseases have garnered significant attention, with studies exploring RV properties at [...] Read more.

Resveratrol (RV), a natural polyphenol found in various plants, exhibits a wide range of bioactive properties and mechanisms of action. Its potential therapeutic benefits in several diseases and, more specifically, in ocular diseases have garnered significant attention, with studies exploring RV properties at cellular, molecular, and physiological levels. Like many natural derivatives, RV can be obtained through various extraction methods from plant sources, with a growing interest in sustainable techniques that align with recent trends in sustainability, circular economy, and green chemistry. This review begins by describing the most efficient and sustainable extraction techniques of RV from natural sources and then delves into its numerous bioactive properties and its synergistic effects with other active substances and drugs. Furthermore, an overview of the scientific literature on RV as a therapeutic agent for ocular diseases, both in its pure form and entrapped in nanoparticulate systems, is provided. Full article

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13 pages, 1001 KiB

Open AccessReview

ChatGPT in Pharmacy Practice: Disruptive or Destructive Innovation? A Scoping Review

by Tácio de Mendonça Lima, Michelle Bonafé, André Rolim Baby and Marília Berlofa Visacri

Sci. Pharm. 2024, 92(4), 58; https://doi.org/10.3390/scipharm92040058 - 21 Oct 2024

Abstract

ChatGPT has emerged as a promising tool for enhancing clinical practice. However, its implementation raises critical questions about its impact on this field. In this scoping review, we explored the utility of ChatGPT in pharmacy practice. A search was conducted in five databases [...] Read more.

ChatGPT has emerged as a promising tool for enhancing clinical practice. However, its implementation raises critical questions about its impact on this field. In this scoping review, we explored the utility of ChatGPT in pharmacy practice. A search was conducted in five databases up to 23 May 2024. Studies analyzing the use of ChatGPT with direct or potential applications in pharmacy practice were included. A total of 839 records were identified, of which 14 studies were included: six tested ChatGPT version 3.5, three tested version 4.0, three tested both versions, one used version 3.0, and one did not specify the version. Only half of the studies evaluated ChatGPT in real-world scenarios. A reasonable number of papers analyzed the use of ChatGPT in pharmacy practice, highlighting both benefits and limitations. The studies indicated that ChatGPT is not fully prepared for use in pharmacy practice due to significant limitations. However, there is great potential for its application in this context in the near future, following further improvements to the tool. Further exploration of its use in pharmacy practice is required, along with proposing its conscious and appropriate utilization. Full article

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25 pages, 1074 KiB

Open AccessReview

Passiflora By-Products: Chemical Profile and Potential Use as Cosmetic Ingredients

by Manuela Victoria Pardo Solórzano, Geison Modesti Costa and Leonardo Castellanos

Sci. Pharm. 2024, 92(4), 57; https://doi.org/10.3390/scipharm92040057 - 18 Oct 2024

Abstract

The cosmetics industry is constantly growing and occupies an important place in South American countries’ economies. Formulations increasingly incorporate ingredients from natural sources to promote sustainable and innovative productions, as well as to gain greater consumer acceptance. According to FAO, waste from post-harvest [...] Read more.

The cosmetics industry is constantly growing and occupies an important place in South American countries’ economies. Formulations increasingly incorporate ingredients from natural sources to promote sustainable and innovative productions, as well as to gain greater consumer acceptance. According to FAO, waste from post-harvest and food processing in developing countries exceeds 40%, generating significant environmental impacts and stimulating interest in adding value to these wastes, particularly in the fruit and vegetable sector in South American countries, thus contributing to the achievement of the UN Sustainable Development Goals (SDGs). By-products from harvesting and fruit processing of Passiflora species such as leaves, stems, peel, and seeds are a source of bioactive compounds; however, most of them are wasted. This study aims to compile reports on the chemical composition of cultivated Passiflora species, find evidence of the cosmetic activity of their extracts, and estimate their potential for inclusion in cosmetic formulations. Full article

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7 pages, 1069 KiB

Open AccessArticle

Evaluation of the Efficacy of Methylene Blue Administration in SARS-CoV-2-Affected Patients: A Proof-of-Concept Phase 2, Randomized, Placebo-Controlled, Single-Blind Clinical Trial

by Beatrice Barda, Bruno Di Mari, Emiliano Soldini, Claudia Di Bartolomeo, Maurizia Bissig, Adriana Baserga, Antonella Robatto, Lorenzo Magenta, Rossella Forlenza and Andreas Cerny

Sci. Pharm. 2024, 92(4), 56; https://doi.org/10.3390/scipharm92040056 - 14 Oct 2024

Abstract

The SARS-CoV-2 pandemic has revolutionized the scientific and medical world in recent years. Methylene blue (MB) is a well-known molecule. The aim of our study was to assess the efficacy of MB against early-phase SARS-CoV-2 infections. All patients with a positive swab for [...] Read more.

The SARS-CoV-2 pandemic has revolutionized the scientific and medical world in recent years. Methylene blue (MB) is a well-known molecule. The aim of our study was to assess the efficacy of MB against early-phase SARS-CoV-2 infections. All patients with a positive swab for SARS-CoV-2 were eligible for the trial. The intervention was a starting dose of 200 mg MB or placebo in the morning and 100 mg in the evening on the first day and afterwards the standard daily dose of 200 mg. Patients were followed up for safety and efficacy until day 84. We analyzed 21 patients for the safety profile and 19 for the efficacy objective: of these, there were 11 in the MB group and 8 in the placebo one. In both groups, patients had undetectable RNA from day 3 and 10 out of 11 subjects in the MB group were virus free by day 12 vs. 6 out of 8 in the placebo one. None of the patients experienced serious adverse events. MB has proved to be a safe and well-tolerated drug. We did not find superiority of efficacy or viral clearance of MB compared to the placebo. Given the good in vitro efficacy, larger studies are needed to assess MB efficacy against COVID-19 in vivo. Full article

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24 pages, 6993 KiB

Open AccessArticle

Human Target Proteins for Benzo(a)pyrene and Acetaminophen (And Its Metabolites): Insights from Inverse Molecular Docking and Molecular Dynamics Simulations

by Yina Montero-Pérez, Nerlis Pájaro-Castro, Nadia Coronado-Posada, Maicol Ahumedo-Monterrosa and Jesus Olivero-Verbel

Sci. Pharm. 2024, 92(4), 55; https://doi.org/10.3390/scipharm92040055 - 8 Oct 2024

Abstract

Acetaminophen (APAP) is a widely used analgesic and antipyretic, whereas benzo(a)pyrene (B[a]P) is a carcinogen with significant global health risks due to environmental exposure. While APAP is generally safe at therapeutic doses, co-exposure to B[a]P can exacerbate its toxicity. This study aimed to [...] Read more.

Acetaminophen (APAP) is a widely used analgesic and antipyretic, whereas benzo(a)pyrene (B[a]P) is a carcinogen with significant global health risks due to environmental exposure. While APAP is generally safe at therapeutic doses, co-exposure to B[a]P can exacerbate its toxicity. This study aimed to identify potential human target proteins for B[a]P and APAP through inverse molecular docking and molecular dynamics simulations. We performed inverse docking with B[a]P, APAP, and three APAP metabolites against 689 human proteins involved in various biological processes. Five proteins were selected based on high docking affinity and their involvement in multiple pathways. Molecular dynamics simulations revealed that B[a]P primarily interacted via hydrophobic and π-stacking interactions with proteins like LXR-β, HSP90α, HSP90β, and AKT1, while AM404 formed hydrogen bonds and hydrophobic interactions. The simulations confirmed that the complexes had high conformational stability, except for protein AKT1. These results provide insights into the potential impacts of B[a]P and AM404 on protein functions and their implications for understanding the toxic effects of combined exposure. Full article

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19 pages, 4020 KiB

Open AccessArticle

Position Matters: Effect of Nitro Group in Chalcones on Biological Activities and Correlation via Molecular Docking

by Alam Yair Hidalgo, Nancy Romero-Ceronio, Carlos Ernesto Lobato-García, Maribel Herrera-Ruiz, Romario Vázquez-Cancino, Omar Aristeo Peña-Morán, Miguel Ángel Vilchis-Reyes, Ammy Joana Gallegos-García, Eric Jaziel Medrano-Sánchez, Oswaldo Hernández-Abreu and Abraham Gómez-Rivera

Sci. Pharm. 2024, 92(4), 54; https://doi.org/10.3390/scipharm92040054 - 8 Oct 2024

Abstract

A series of nine nitro group-containing chalcones were synthesized to investigate their anti-inflammatory and vasorelaxant activities via in vivo, ex vivo, and in silico studies. The anti-inflammatory effects of the compounds were evaluated via a TPA-induced mouse ear edema model, and the vasorelaxant [...] Read more.

A series of nine nitro group-containing chalcones were synthesized to investigate their anti-inflammatory and vasorelaxant activities via in vivo, ex vivo, and in silico studies. The anti-inflammatory effects of the compounds were evaluated via a TPA-induced mouse ear edema model, and the vasorelaxant effects were evaluated via an isolated organ model in addition to molecular docking studies. The compounds with the highest anti-inflammatory activity were 2 (71.17 ± 1.66%), 5 (80.77 ± 2.82%), and 9 (61.08 ± 2.06%), where the nitro group is located at the ortho position in both rings, as confirmed by molecular docking with COX-1 and COX-2. The compounds with the highest vasorelaxant activity were 1 (81.16 ± 7.55%), lacking a nitro group, and 7 (81.94 ± 2.50%), where the nitro group is in the para position of the B ring; both of these compounds interact with the eNOS enzyme during molecular docking. These results indicate that the position of the nitro group in the chalcone plays an important role in these anti-inflammatory and vasorelaxant activities. Full article

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18 pages, 2428 KiB

Open AccessArticle

Cannabigerol Reduces Acute and Chronic Hypernociception in Animals Exposed to Prenatal Hypoxia-Ischemia

by Bismarck Rezende, Kethely Lima Marques, Filipe Eloi Alves de Carvalho, Vitória Macario de Simas Gonçalves, Barbara Conceição Costa Azeredo de Oliveira, Gabriela Guedes Nascimento, Yure Bazilio dos Santos, Fernanda Antunes, Penha Cristina Barradas, Fabrícia Lima Fontes-Dantas and Guilherme Carneiro Montes

Sci. Pharm. 2024, 92(3), 53; https://doi.org/10.3390/scipharm92030053 - 23 Sep 2024

Abstract

Cannabigerol (CBG), a phytocannabinoid, has shown promise in pain management. Previous studies by our research group identified an increase in pain sensitivity as a consequence of prenatal hypoxia-ischemia (HI) in an animal model. This study aimed to investigate the efficacy of CBG in [...] Read more.

Cannabigerol (CBG), a phytocannabinoid, has shown promise in pain management. Previous studies by our research group identified an increase in pain sensitivity as a consequence of prenatal hypoxia-ischemia (HI) in an animal model. This study aimed to investigate the efficacy of CBG in acute and chronic hyperalgesia induced by prenatal HI. A pharmacological screening was first conducted using hot plate and open-field tests to evaluate the antinociceptive and locomotor activities of animals administered with a 50 mg/kg oral dose of cannabis extract with a high CBG content. Prenatal HI was induced in pregnant rats, and the offspring were used to evaluate the acute antinociceptive effect of CBG in the formalin-induced peripheral pain model, while chronic antinociceptive effects were observed through spinal nerve ligation (SNL) surgery, a model used to induce neuropathic pain. Our results show that CBG exhibited an antinociceptive effect in the hot plate test without affecting the animals’ motor function in the open-field test. CBG significantly reduced formalin-induced reactivity in HI offspring during both the neurogenic and inflammatory phases. CBG treatment alleviated thermal and mechanical hypernociception induced by SNL. Biomolecular analysis revealed CBG’s ability to modulate expression, particularly reducing TNFα and Nav1.7 in HI male and female rats, respectively. These results highlight CBG as a potential antinociceptive agent in acute and chronic pain models, suggesting it as a promising therapeutic option without inducing motor impairment. Further research is needed to fully elucidate its mechanisms and clinical applications in pain management. Full article

(This article belongs to the Topic Cannabis, Cannabinoids and Its Derivatives)

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13 pages, 3538 KiB

Open AccessArticle

Natural Antioxidants from Acmella oleracea Extract as Dermatocosmetic Actives

by Claudia Maxim, Alexandra Cristina Blaga, Ramona Cimpoeșu, Inga Zinicovscaia, Alexandra Peshkova, Maricel Danu, Ana Simona Barna and Daniela Suteu

Sci. Pharm. 2024, 92(3), 52; https://doi.org/10.3390/scipharm92030052 - 19 Sep 2024

Abstract

Compounds from plant extracts make dermatocosmetic products more effective as they avoid the adaptation and resistance of the organism and achieve a synergistic effect of the molecular properties of interest. Acmella oleracea extract is considered to have great potential in preventing oxidative damage [...] Read more.

Compounds from plant extracts make dermatocosmetic products more effective as they avoid the adaptation and resistance of the organism and achieve a synergistic effect of the molecular properties of interest. Acmella oleracea extract is considered to have great potential in preventing oxidative damage and improving the appearance of the skin. The purpose of this article is to support the product formulated by preliminary studies of two types of O/W emulsions with 3% and 5% concentrations of Acmella oleracea extract. Physico-chemical methods were performed to evaluate the stability, microbiological control, rheological behavior and diffusion through the membrane. Good homogeneity, structural strength and flexibility, adequate skin diffusion, and high physico-chemical and microbiological stability were confirmed. The conclusions lead to the idea that these results require further in vivo studies as well as studies of toxicity and cytotoxicity to obtain the necessary data to place this product on the market. Full article

(This article belongs to the Topic New Compounds Discovery and Development in Medicine — Advances in Research on Potential Therapeutic Agents and Drug Candidates, 2nd Edition)

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18 pages, 2964 KiB

Open AccessArticle

Targeted Gene Delivery to Muscle Cells In Vitro and In Vivo Using Electrostatically Stabilized DNA—Peptide Complexes

by Anna Egorova, Sergei Chepanov, Sergei Selkov, Igor Kogan and Anton Kiselev

Sci. Pharm. 2024, 92(3), 51; https://doi.org/10.3390/scipharm92030051 - 14 Sep 2024

Abstract

Genetic constructs must be delivered selectively to target tissues and intracellular compartments at the necessary concentrations in order to achieve the maximum therapeutic effect in gene therapy. Development of targeted carriers for non-viral delivery of nucleic acids into cells, including those in muscle, [...] Read more.

Genetic constructs must be delivered selectively to target tissues and intracellular compartments at the necessary concentrations in order to achieve the maximum therapeutic effect in gene therapy. Development of targeted carriers for non-viral delivery of nucleic acids into cells, including those in muscle, which is one of the most challenging tissues to transfect in vivo, remains a topical issue. We have studied ternary complexes of plasmid DNA and an arginine–histidine-rich peptide-based carrier coated with a glutamate–histidine-rich polymer bearing skeletal muscle targeting peptide (SMTP) for the gene delivery to muscle tissue. The relaxation of the ternary complexes after polyanion treatment was assessed using the ethidium bromide displacement assay. The developed polyplexes were used to transfect C2C12 myoblasts in full-media conditions, followed by analysis of their toxic properties using the Alamar Blue assay and expression analysis of lacZ and GFP reporter genes. After delivering plasmids containing the GFP and lacZ genes into the femoral muscles of mdx mice, which are model of Duchenne muscular dystrophy, GFP fluorescence and β-galactosidase activity were detected. We observed that the modification of ternary polyplexes with 10 mol% of SMTP ligand resulted in a 2.3-fold increase in lacZ gene expression when compared to unmodified control polyplexes in vivo. Thus, we have demonstrated that the developed DNA/carrier complexes and SMTP-modified coating are nontoxic, are stable against polyanion-induced relaxation, and can provide targeted gene delivery to muscle cells and tissues. The results of this study are useful for a range of therapeutic applications, from immunization to amelioration of inherited neuromuscular diseases. Full article

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25 pages, 4244 KiB

Open AccessArticle

Back to Nature: Development and Optimization of Bioinspired Nanocarriers for Potential Breast Cancer Treatment

by Sally Safwat, Rania M. Hathout, Rania A. H. Ishak and Nahed D. Mortada

Sci. Pharm. 2024, 92(3), 50; https://doi.org/10.3390/scipharm92030050 - 2 Sep 2024

Abstract

This study focuses on the preparation and optimization of caffeic acid (CA)-loaded casein nanoparticles (CS NPs) via the Box–Behnken design (BBD) for potential applications in cancer treatment. CS NPs were loaded with CA as a promising anti-cancer molecule. Non-hazardous green materials were exploited [...] Read more.

This study focuses on the preparation and optimization of caffeic acid (CA)-loaded casein nanoparticles (CS NPs) via the Box–Behnken design (BBD) for potential applications in cancer treatment. CS NPs were loaded with CA as a promising anti-cancer molecule. Non-hazardous green materials were exploited for nanoparticle fabrication. The BBD was used, followed by a desirability function to select the optimum formulation. The BBD was adopted as it avoids the runs implemented in extreme conditions, hence making it suitable for proteins. CS NPs were characterized regarding particle size (PS), size distribution (PDI), zeta potential (ZP), drug entrapment, morphology using TEM, differential scanning calorimetry, molecular docking, in vitro release, and cytotoxicity studies. PS, PDI, and ZP had significant responses, while EE% was insignificant. The suggested models were quadratic with high fitting. Optimized NPs showed PS = 110.31 ± 1.02 nm, PDI = 0.331 ± 0.029, ZP = −23.94 ± 1.64 mV, and EE% = 95.4 ± 2.56%. Molecular modeling indicated hydrophobic and electrostatic interactions between CA and CS, accounting for the high EE%. Almost spherical particles were realized with a sustained CA release pattern. Optimized NPs effectively suppressed the growth of MCF-7 cell lines by scoring the lowest IC50 = 78.45 ± 1.7 µg/mL. A novel combination of bioinspired-derived materials was developed for use in breast cancer treatment. Full article

(This article belongs to the Topic Complementary Strategies in Drug Delivery: From Particle Engineering to System Optimization)

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