Scientia Pharmaceutica

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

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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

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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

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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

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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

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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

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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

Viewed by 1277

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

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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

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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

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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

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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

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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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Sci. Pharm., Volume 92, Issue 4 (December 2024) – 12 articles

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