Pharmaceuticals最新文献

The imbalance in the production of reactive oxygen species (ROS) with endogenous antioxidant capacity leads to oxidative stress, which drives many disorders, especially in the skin. In such conditions, supplementing exogenous antioxidants may help the body prevent the negative effect of ROS. However, the skin, as the outermost barrier of the body, provides a perfect barricade, making the antioxidant delivery complicated. Several strategies have been developed to enhance the penetration of antioxidants through the skin, one of which is nanotechnology. This review focuses on utilizing several nanocarrier systems, including nanoemulsions, liposomes, solid lipid nanoparticles (SLNs), nanostructured lipid carriers (NLCs), and polymeric nanoparticles, for transporting antioxidants into the skin. We also reveal ROS formation in the skin and the role of antioxidant therapy, as well as the natural sources of antioxidants. Furthermore, we discuss the clinical application of topical antioxidant therapy concomitantly with the current status of using nanotechnology to deliver topical antioxidants. This review will accelerate the advancement of topical antioxidant therapy.

Background: This study explores the potential for the synthesis of peptide nanosystems comprising spinorphin molecules (with rhodamine moiety: Rh-S, Rh-S5, and Rh-S6) conjugated with nanoparticles (AuNPs), specifically peptide Rh-S@AuNPs, peptide Rh-S5@AuNPs, and peptide Rh-S6@AuNPs, alongside a comparative analysis of the biological activities of free and conjugated peptides. The examination of the microstructural characteristics of the obtained peptide systems and their physicochemical properties constitutes a key focus of this study. Methods: Zeta (ζ) potential, Fourier transformation infrared (FTIR) spectroscopy, circular dichroism (CD), scanning electron microscopy (SEM-EDS), transmission electron microscopy (TEM), and UV-Vis spectrophotometry were employed to elucidate the structure-activity correlations of the peptide@nano AuNP systems. Results: The zeta potential values for all the Rh-S@AuNPs demonstrate that the samples are electrically stable and resistant to flocculation and coagulation. The absorption of energy quanta from UV-Vis radiation by the novel nanopeptide systems does not substantially influence the distinctive signal of AuNPs, which is situated at around 531 nm. The FTIR measurements indicate the signals associated with the unique functional groups of the peptides, whereas circular dichroism verifies the synthesis of the conjugated nanocomposites of the spinorphin@AuNP type. An analysis of the SEM and TEM data revealed that most AuNPs have a spherical morphology, with an average diameter of around 21.92 ± 6.89 nm. The results of the in vivo studies showed promising findings regarding the anticonvulsant properties of the nanocompounds, especially the Rh-S@AuNP formulation. Conclusions: All the nanocompounds tested demonstrated the ability to reduce generalized tonic-clonic seizures. This suggests that these formulations may effectively target the underlying neuronal hyperexcitability. In addition, the prepared Rh-S@AuNP formulations also showed anticonvulsant activity in the maximal electroshock test performed in mice, which was evident after systemic (intraperitoneal) administration. The study's findings indicate that conjugates can be synthesized via a straightforward process, rendering them potential therapeutic agents with biological activity.

Background/Objectives: DPP4 is an enzyme with multiple natural substrates and probable involvement in various mechanisms. It constitutes a drug target for the treatment of diabetes II, although, also related to other disorders. While a number of drugs with competitive inhibitory action and covalent binding capacity are available, undesired side effects exist partly attributed to drug kinetics, and research for finding novel, potent, and safer compounds continues. Despite the research, a low number of uncompetitive and non-competitive inhibitors, which could be of worth for pharmaceutical and mechanism studies, was mentioned. Methods: In the present study sixteen 3-(benzo[d]thiazol-2-yl)-2-aryl thiazolidin-4-ones were selected for evaluation, based on structural characteristics and docking analysis and were tested in vitro for DPP4 inhibitory action using H-Gly-Pro-amidomethyl coumarin substrate. Their mode of inhibition was also in vitro explored. Results: Twelve compounds exhibited IC₅₀ values at the nM range with the best showing IC₅₀ = 12 ± 0.5 nM, better than sitagliptin. Most compounds exhibited a competitive mode of inhibition. Inhibition modes of uncompetitive, non-competitive, and mixed type were also identified. Docking analysis was in accordance with the in vitro results, with a linear correlation of logIC₅₀ with a Probability of Binding Factor(PF) derived using docking analysis to a specific target box and to the whole enzyme. According to the docking results, two probable sites of binding for uncompetitive inhibitors were highlighted in the wider area of the active site and in the propeller loop. Conclusions: Potent inhibitors with IC₅₀ at the nM range and competitive, non-competitive, uncompetitive, and mixed modes of action, one better than sitagliptin, were found. Docking analysis was used to estimate probable sites and ways of binding. However, crystallographic or NMR studies are needed to elucidate the exact way of binding especially for uncompetitive and non-competitive inhibitors.

Artificial Intelligence (AI) has the disruptive potential to transform patients' lives via innovations in pharmaceutical sciences, drug development, clinical trials, and manufacturing. However, it presents significant challenges, ethical concerns, and risks across sectors and societies. AI's rapid advancement has revealed regulatory gaps as existing public policies struggle to keep pace with the challenges posed by these emerging technologies. The term AI itself has become commonplace to argue that greater "human oversight" for "machine intelligence" is needed to harness the power of this revolutionary technology for both potential and risk management, and hence to call for more practical regulatory guidelines, harmonized frameworks, and effective policies to ensure safety, scalability, data privacy, and governance, transparency, and equitable treatment. In this review paper, we employ a holistic multidisciplinary lens to survey the current regulatory landscape with a synopsis of the FDA workshop perspectives on the use of AI in drug and biological product development. We discuss the promises of responsible data-driven AI, challenges and related practices adopted to overcome limitations, and our practical reflections on regulatory oversight. Finally, the paper outlines a path forward and future opportunities for lawful ethical AI. This review highlights the importance of risk-based regulatory oversight, including diverging regulatory views in the field, in reaching a consensus.

Background/Objectives: Mirtazapine (MRZ) is a psychotropic drug prescribed to manage serious sorts of depression. By virtue of its extensive initial-pass metabolic process with poor water solubility, the ultimate bioavailability when taken orally is a mere 50%, necessitating repeated administration. The current inquiry intended to fabricate nose-to-brain chitosan-grafted cationic leciplexes of MRZ (CS-MRZ-LPX) to improve its pharmacokinetic weaknesses and boost the pharmacodynamics aspects. Methods: Primarily, MRZ-loaded leciplexes (MRZ-LPXs) were fabricated and tailored employing a central composite design (CCD). Vesicle diameter size (VS), entrapment efficiency (EE %), cumulative MRZ release percentage (CMRZR %), and total quantity penetrating after twenty-four hours (Q24) were the four parameters assessed. Then, the determined optimum formulation was coated with chitosan (CS-MRZ-LPX) and utilized in pharmacodynamics investigations and in vivo biologic distribution studies in Wistar male rats. Results: The customized MRZ-LPX formulation had a diameter size of 186.2 ± 3.5 nm and drug EE of 45.86 ± 0.76%. Also, the tailored MRZ-LPX formulation had a cumulative amount of MRZ released of 76.66 ± 3.06% and the total Q24 permeated was 383.23 ± 13.08 µg/cm². Intranasal delivery of the tailored CS-MRZ-LPX revealed notably superior pharmacokinetic attributes inside the brain and circulation compared to the orally administered MRZ suspension and the intranasal free drug suspension (p < 0.05); the relative bioavailability was 370.9% and 385.6% for plasma and brain, respectively. Pharmacodynamics' and immunohistopathological evaluations proved that optimum intranasal CS-MRZ-LPX boosted antidepressant activity compared to the oral and free nasal drug administration. Conclusions: CS-MRZ-LPX tailored formulation can potentially be regarded as a prospective nano platform to boost bioavailability and enhance pharmacodynamics efficacy. Ultimately, intranasal CS-MRZ-LPX can be considered a promising avenue for MRZ targeted brain delivery as an antidepressant.

Background/objectives: New drugs are required for the treatment of liver cancers and protozoal parasite infections. Analogs of the known anticancer active and antileishmanial 2',4',6'-trimethoxychalcone SU086 were prepared and investigated.

Methods: The chalcones were prepared according to the Claisen-Schmidt condensation protocol and analyzed. They were tested for activity against two liver cancer cell lines (HepG2 and HuH-7) and protozoal parasites (Toxoplasma gondii and Leishmania major). Unspecific toxicity and expression of Hsp90 and Hsp70 upon treatment were analyzed in liver cancer cells.

Results: A new chalcone, 2',4',6'-trimethoxy-3-pentafluorosulfanylchalcone (246TMP-3SF5), with a pentafluorosulfanyl (SF₅) substituent showed pronounced activities against liver cancer cells and T. gondii parasites which were superior to the activities of the parent chalcone SU086 in these models. In contrast, SU086 and its anthracene analog 2',4',6'-trimethoxy-9-anthracenylchalcone (246TMP-Anth) were most active against L. major promastigotes. The new SF₅-substituted chalcone behaved like the known Hsp90 inhibitor 17-AAG and upregulated Hsp70 expression in liver cancer cells.

Conclusions: The SF₅-substituted SU086 analog has potential to become a new drug for the therapy of hepatoma and toxoplasmosis.

The complexity of our life experiences and the rapid progress in science and technology clearly necessitate reflections from the humanities. The ever-growing intersection between science and society fosters the emergence of novel interdisciplinary fields of research. During the past decade, Medical Humanities arose to meet the need to unravel hidden information beyond technology-driven and fact-based medicine. In the present paper, we put forward the hypothesis that there is a similar requirement to develop Pharmaceutical Humanities as an academic discipline within pharmacy and pharmaceutical biology. Based on Thomas Kuhn's epistemological theory on the structure of scientific revolutions, one may argue that a paradigm change for Pharmaceutical Humanities might open new levels of insight. Many complex diseases (e.g., cancer, neurological diseases, and mental disorders) remain uncurable for many patients by current pharmacotherapies, and the old beaten paths in our therapeutic thinking may at least partly have to be left behind. By taking examples from Pharmaceutical Biology, we attempt to illustrate that the transdisciplinary dialogue with the humanities is fertile ground not only for enlarging our understanding of disease-related conditions but also for exploring new ways of combatting diseases. In this context, we discuss aspects related to traditional herbal medicine, fair access and benefit sharing of indigenous knowledge about medicinal plants, post-traumatic stress syndrome, the opioid crisis, stress myocardiopathy (broken heart syndrome), and global environmental pollution with microplastics. We also explore possibilities for a narrative turn in pharmacy. The urgent need for inter- and transdisciplinary solutions to pressing health-related problems in our society may create a scholarly atmosphere for the establishment of Pharmaceutical Humanities as a fruitful terrain to respond to the current demands of both science and society.

Background/Objectives:Argemone platyceras Link & Otto, an endemic plant of Mexico, is widely distributed in the central area of the country, mainly in the states of Tlaxcala, Puebla, and the State of Mexico. Ethnobotanical studies in different communities of these states have demonstrated that it is primarily used to treat diabetes and mental illnesses, such as "los nervios" (nerves) and "el ansia" (anxiety); these terms are used in traditional medicine, but it is accepted that they refer to anxiety disorders. This study aimed to validate the traditional use of aerial parts of A. platyceras Link & Otto in treating these illnesses. Methods: a standardized acidic method to obtain alkaloids was used to obtain an extract (AlkExt), which was tested in adult male Swiss Webster mice in the tail suspension (TST) and forced swimming (FST) tests. Results: AlkExt was analyzed using mass spectrometry techniques (DI-ESI and UHPLC-MS) to detect 2,3',4,5'-Tetramethoxystilbene (m/z 301.14, 3%), scoulerine (m/z 328.16, 19.8%), tetrahydro-columbamine (m/z 342.17, 28.8%), 8-(hydroxymethyl)-2,10-dimethoxy-6,8,13,13a-tetrahydro-5H-isoquinolino[2,1-b]isoquinoline-1,11-diol (m/z 358.17, 22.8%), and glaucine (m/z 356.19, 11.1%); these were assayed in a single oral administration of AlkExt, which caused robust anxiolytic- and antidepressant-like effects without affecting the spontaneous ambulatory activity of the mice. Conclusions: The easy and standardized AlkExt analyzed in pharmaceuticals assays in this study strongly suggest its therapeutic potential to treat the comorbidity of anxiety and depression disorders and support further investigations in people with these diseases.

Background: Osteoporosis is characterized by the microstructural depletion of bone tissue and decreased bone density, leading to an increased risk of fractures. Cotoneaster wilsonii Nakai, an endemic species of the Korean Peninsula, grows wild in Ulleungdo. In this study, we aimed to investigate the effects of C. wilsonii and its components on osteoporosis.

Methods and results: The alkaline phosphatase (ALP) activity of C. wilsonii extracts and fractions was evaluated in MC3T3-E1 pre-osteoblasts, and the n-hexane fraction (CWH) showed the best properties for ALP activity. The effects of the CWH on bone formation were assessed in MC3T3-E1 cells and ovariectomized mice. Biochemical assays and histological analyses focused on the signaling activation of osteoblast differentiation and osteogenic markers, such as ALP, collagen, and osterix. The CWH significantly activated TGF-β and Wnt signaling, enhancing osteoblast differentiation and bone matrix formation. Notably, CWH treatment improved micro-CT indices, such as femoral bone density, and restored serum osteocalcin levels compared to OVX controls.

Conclusions: These results highlight the potential of the C. wilsonii Nakai n-hexane fraction as a promising therapeutic agent for managing osteoporosis.

Background: Camellia oleifera Abel (C. oleifera) is widely cultivated and serves as an important source of edible oil. Yet, during oil production, pruned branches generate significant waste and contribute to environmental pollution.

Objectives: In this work, we obtain a natural polysaccharide from the branches of C. oleifera and optimize its extraction using Box-Behnken design (BBD), which is a statistical method commonly used in response surface methodology. Additionally, we study its properties, such as monosaccharide composition, structural features, antioxidant, and anti-inflammatory abilities.

Results: BBD was employed to optimize polysaccharide extraction (solid-liquid ratio = 1:40; 90 °C; 130 min) for a higher yield. After purification, the major monosaccharides of branches of C. oleifera's polysaccharide (CBP) were disclosed as glucose and galactose. Subsequent structural features of CBP were measured. The antioxidant and anti-inflammatory abilities were measured. The highly scavenging rates of the 2,2-diphenyl-1-picrylhydrazyl and hydroxyl radicals, with the chelating capacity of Fe²⁺, indicate potent antioxidant activity of CBP.

Conclusions: In general, CBP demonstrated significant anti-inflammatory activity with down-regulating the expression of IL-6 and IL-1β in the LPS-induced macrophage RAW264.7 model. This bioactive polysaccharide adds value to waste branches by offering a novel approach to waste recycling and the development of C. oleifera.