Hasil untuk "Pharmacy and materia medica"

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DOAJ Open Access 2026
Recent Advances in Nanoparticle-Based Drug Delivery Strategies to Cross the Blood–Brain Barrier in Targeted Treatment of Alzheimer’s Disease

Hoa Le, Giang T. T. Vu, Amos Abioye et al.

The blood–brain barrier (BBB) is a major obstacle to the development of brain-targeted drug delivery systems, restricting greater than 98% of small molecules (<500 Da) and virtually all large-molecule drugs from entering the brain tissues from the bloodstream, resulting in suboptimal drug doses and therapeutic failure in the treatment of Alzheimer’s disease (AD). However, the advent of nanotechnology has provided significant solutions to the BBB challenges, enabling particle size reduction, enhanced drug solubility, reduced premature drug degradation, extended and sustained drug release, enhanced drug transport across the BBB, increased drug target specificity and enhanced therapeutic efficacy. In corollary, a library of brain-targeted surface-functionalized nanotherapeutics has been widely reported in the current literature. These promising in vitro, in vivo and pre-clinical results from the existing literature provide quantitative evidence for the relative clinical utility of each of the techniques, indicating remarkable capacity for brain-targeted carrier systems; many of them are still being tested in human clinical trials. However, despite the recorded research successes in drug transport across the BBB, there are currently no clinically proven medications that can slow or reverse the progression of AD because most of the novel therapeutics have not been successful during the clinical trials. Therefore, the main option for the treatment of AD is symptomatic treatment using cholinesterase inhibitors and N-methyl-D-aspartate (NMDA) receptor antagonists. Although these therapies help to alleviate symptoms of AD and improve patients’ quality of life, they neither slow the progression of disease nor cure it. Thus, an effective disease-modifying therapy for the treatment of AD is an unmet clinical need. It is apparent that a deeper understanding of the structural complexity and controlling dynamic functions of the BBB in tandem with a comprehensive elucidation of AD pathogenesis are crucial to the development of novel nanocarriers for the effective treatment of AD. Therefore, this narrative review describes the contextual analysis of several promising strategies that enhance brain-targeted drug delivery across the BBB in AD treatment and recent research efforts on two major AD biomarkers that have revolutionized AD diagnosis, amyloid-beta plaques and phosphorylated tau protein tangle, as potential targets in AD drug development. This has led to the Food and Drug Administration (FDA)’s approval of two intravenous (IV) anti-amyloid monoclonal antibodies, Lecanemab (Leqembi<sup>®</sup>) and Donanemab (Kisunla<sup>®</sup>), which were developed based on the Aβ cascade hypothesis for the treatment of early AD. This review also discusses the recent shift in the Aβ cascade hypothesis to Aβ oligomer (conformer), a soluble intermediate of Aβ, which is the most toxic mediator of AD and could be the most potent drug target in the future for a more accurate and effective drug development model for the treatment of AD. Furthermore, various promising nanoparticle-based drug carriers (therapeutic nanoparticles) that were developed from intensive research are discussed, including their clinical utility, challenges and prospects in the treatment of AD. Overall, it suffices to state that the advent of nanotechnology provided several innovative techniques for overcoming the BBB and improving drug delivery to the brain; however, their long-term biosafety is a relevant concern.

Pharmacy and materia medica
arXiv Open Access 2025
Provably Small Portfolios for Multiobjective Optimization with Application to Subsidized Facility Location

Swati Gupta, Jai Moondra, Mohit Singh

Many multiobjective real-world problems, such as facility location and bus routing, become more complex when optimizing the priorities of multiple stakeholders. These are often modeled using infinite classes of objectives, e.g., $L_p$ norms over group distances induced by feasible solutions in a fixed domain. Traditionally, the literature has considered explicitly balancing `equity' (or min-max) and `efficiency' (or min-sum) objectives to capture this trade-off. However, the structure of solutions obtained by such modeling choices can be very different. Taking a solution-centric approach, we introduce the concept of provably small set of solutions $P$, called a {\it portfolio}, such that for every objective function $h(\cdot)$ in the given class $\mathbf{C}$, there exists some solution in $P$ which is an $α$-approximation for $h(\cdot)$. Constructing such portfolios can help decision-makers understand the impact of balancing across multiple objectives. Given a finite set of base objectives $h_1, \ldots, h_N$, we give provable algorithms for constructing portfolios for (1) the class of conic combinations $\mathbf{C} = \{\sum_{j \in [N]}λ_j h_j: λ\ge 0\}$ and for (2) any class $\mathbf{C}$ of functions that interpolates monotonically between the min-sum efficiency objective (i.e., $h_1 + \ldots + h_N$) and the min-max equity objective (i.e., $\max_{j \in [N]} h_j$). Examples of the latter are $L_p$ norms and top-$\ell$ norms. As an application, we study the Fair Subsidized Facility Location (FSFL) problem, motivated by the crisis of medical deserts caused due to pharmacy closures. FSFL allows subsidizing facilities in underserved areas using revenue from profitable locations. We develop a novel bicriteria approximation algorithm and show a significant reduction of medical deserts across states in the U.S.

en cs.DS
arXiv Open Access 2025
Analise de Desaprendizado de Maquina em Modelos de Classificacao de Imagens Medicas

Andreza M. C. Falcao, Filipe R. Cordeiro

Machine unlearning aims to remove private or sensitive data from a pre-trained model while preserving the model's robustness. Despite recent advances, this technique has not been explored in medical image classification. This work evaluates the SalUn unlearning model by conducting experiments on the PathMNIST, OrganAMNIST, and BloodMNIST datasets. We also analyse the impact of data augmentation on the quality of unlearning. Results show that SalUn achieves performance close to full retraining, indicating an efficient solution for use in medical applications.

en eess.IV, cs.AI
DOAJ Open Access 2024
Myrtucommulones and Related Acylphloroglucinols from Myrtaceae as a Promising Source of Multitarget SARS-CoV-2 Cycle Inhibitors

Simony Carvalho Mendonça, Brendo Araujo Gomes, Mariana Freire Campos et al.

The LABEXTRACT plant extract bank, featuring diverse members of the Myrtaceae family from Brazilian hot spot regions, provides a promising avenue for bioprospection. Given the pivotal roles of the Spike protein and 3CL<sup>pro</sup> and PL<sup>pro</sup> proteases in SARS-CoV-2 infection, this study delves into the correlations between the Myrtaceae species from the Atlantic Forest and these targets, as well as an antiviral activity through both <i>in vitro</i> and <i>in silico</i> analyses. The results uncovered notable inhibitory effects, with <i>Eugenia prasina</i> and <i>E. mosenii</i> standing out, while <i>E. mosenii</i> proved to be multitarget, presenting inhibition values above 72% in the three targets analyzed. All extracts inhibited viral replication in Calu-3 cells (EC<sub>50</sub> was lower than 8.3 µg·mL<sup>−1</sup>). Chemometric analyses, through LC-MS/MS, encompassing prediction models and molecular networking, identified potential active compounds, such as myrtucommulones, described in the literature for their antiviral activity. Docking analyses showed that one undescribed myrtucommulone (m/z 841 [M − H]<sup>−</sup>) had a higher fitness score when interacting with the targets of this study, including ACE2, Spike, PL<sup>pro</sup> and 3CL<sup>pro</sup> of SARS-CoV-2. Also, the study concludes that Myrtaceae extracts, particularly from <i>E. mosenii</i> and <i>E. prasina</i>, exhibit promising inhibitory effects against crucial stages in SARS-CoV-2 infection. Compounds like myrtucommulones emerge as potential anti-SARS-CoV-2 agents, warranting further exploration.

Medicine, Pharmacy and materia medica
DOAJ Open Access 2024
Assessing the osteoporotic risk markers in apparently healthy adults

Aakriti Chahal, Anjali Dhama, Abhishek Chahal

Background: Bone is a dynamic tissue undergoing continuous turnover. Proper bone remodeling and good bone health are crucial for the overall well-being of individuals. Among a numerous markers depicting bone health, Vitamin D, Vitamin D binding protein (VDBP) and bone-specific alkaline phosphatase (BALP) are the potential ones. Vitamin D exerts its principle actions by regulating the intestinal absorption of calcium, renal reabsorption of calcium and phosphate and mineralization of bones. VDBP may alter bone health by regulating vitamin D bioavailability (VDBP-bound vitamin is thought to be relatively unavailable to target tissues). BALP, synthesized by the osteoblasts play a major role in bone formation by hydrolysing inorganic pyrophosphate (which is a naturally occurring inhibitor of mineralization). Thus, being pivotal regulators of bone mineralization Vitamin D, VDBP, and BALP can be used as highly specific and vital indices for assessing the rate of overall bone turnover. Altered bone metabolism leads to an array of disorders including increased osteoporotic risk in future. Aims and Objectives: The present study was planned to assess these bone health parameters (Vitamin D, VDBP and BALP) in apparently healthy individuals. Materials and Methods: For this study, 40 male and 40 female healthy volunteers (of age group 25–45 years) were enrolled (n = 80). The Institutional Ethics Committee approval has been taken before the commencement of the study. After informed consent from patient, blood samples were collected and analyzed for routine biochemistry and special bone parameters. Data was analysed statistically using SPSS software. Results: The study groups showed low levels of serum vitamin D and VDBP and increased BALP levels. Furthermore, a significant correlation was observed among VDBP and BALP. Conclusion: From this study, we conclude that Vitamin D, VDBP, and BALP act as potential biomarkers for bone health. [Natl J Physiol Pharm Pharmacol 2024; 14(1.000): 21-26]

Therapeutics. Pharmacology, Pharmacy and materia medica
DOAJ Open Access 2024
Population Pharmacokinetic–Pharmacodynamic Analysis of a Reserpine-Induced Myalgia Model in Rats

Gloria M. Alfosea-Cuadrado, Javier Zarzoso-Foj, Albert Adell et al.

(1) Background: Fibromyalgia syndrome (FMS) is a chronic pain condition with widespread pain and multiple comorbidities, for which conventional therapies offer limited benefits. The reserpine-induced myalgia (RIM) model is an efficient animal model of FMS in rodents. This study aimed to develop a pharmacokinetic–pharmacodynamic (PK–PD) model of reserpine in rats, linking to its impact on monoamines (MAs). (2) Methods: Reserpine was administered daily for three consecutive days at dose levels of 0.1, 0.5, and 1 mg/kg. A total of 120 rats were included, and 120 PK and 828 PD observations were collected from 48 to 96 h after the first dose of reserpine. Non-linear mixed-effect data analysis was applied for structural PK–PD model definition, variability characterization, and covariate analysis. (3) Results: A one-compartment model best described reserpine in rats (V = 1.3 mL/kg and CL = 4.5 × 10<sup>−1</sup> mL/h/kg). A precursor-pool PK–PD model (k<sub>in</sub> = 6.1 × 10<sup>−3</sup> mg/h, k<sub>p</sub> = 8.6 × 10<sup>−4</sup> h<sup>−1</sup> and k<sub>out</sub> = 2.7 × 10<sup>−2</sup> h<sup>−1</sup>) with a parallel transit chain (k<sub>0</sub> = 1.9 × 10<sup>−1</sup> h<sup>−1</sup>) characterized the longitudinal levels of MA in the prefrontal cortex, spinal cord, and amygdala in rats. Reserpine stimulates the degradation of MA from the pool compartment (Slope<sub>1</sub> = 1.1 × 10<sup>−1</sup> h) and the elimination of MA (Slope<sub>2</sub> = 1.25 h) through the transit chain. Regarding the reference dose (1 mg/kg) of the RIM model, the administration of 4 mg/kg would lead to a mean reduction of 65% (C<sub>max</sub>), 80% (C<sub>min</sub>), and 70% (AUC) of MA across the brain regions tested. (4) Conclusions: Regional brain variations in neurotransmitter depletion were identified, particularly in the amygdala, offering insights for therapeutic strategies and biomarker identification in FMS research.

Pharmacy and materia medica
DOAJ Open Access 2024
Investigation of cyclodextrin as potential carrier for lycopene

Kulawik Anna, Rosiak Natalia, Miklaszewski Andrzej et al.

Lycopene is a carotenoid with high antioxidant activity. Numerous studies show its positive effects in the prevention and amelioration of many diseases. However, due to its lack of water solubility, its use is very limited. Developing a formulation with lycopene with favorable therapeutic parameters will allow for a more effective use of this ingredient. The aim of this study was therefore to use supercritical phase extraction to obtain lycopene-containing preparations, and to obtain complexes of the extract with cyclodextrins to improve its solubility and increase its antioxidant potential. Lycopene-containing extracts were obtained by ultrasound-assisted acetone extraction and supercritical phase extraction. The supercritical extract was combined with g-cyclodextrin, b-cyclodextrin and 2-hydroxypropyl-b-cyclodextrin. Attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) and X-ray diffraction (XRD) analyses were performed for the obtained systems and extracts. A paddle apparatus was used to evaluate the in vitro dissolution, and the samples collected were analysed by HPLC. The antioxidant activity was assessed using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical method. The results show that cyclodextrins increase the dissolution of lycopene into an acidic environment and enhance the antioxidant potential of the compound. We conclude that the development of a formulation containing a combination of lycopene obtained by supercritical extraction and cyclodextrin will allow for a wider and more effective use of this ingredient.

Pharmacy and materia medica
arXiv Open Access 2024
Optical detection of bacterial cells on stainless-steel surface with a low-magnification light microscope

Yuzhen Zhang, Zili Gao, Lili He

A Rapid and cost-effective method for detecting bacterial cells on surfaces is critical to protect public health from various aspects, including food safety, clinical hygiene, and pharmacy quality. Herein, we first established an optical detection method based on a gold chip coating with 3-mercaptophenylboronic acid (3-MPBA) to capture bacterial cells, which allows for the detection and quantification of bacterial cells with a standard light microscope under low-magnification (10 fold) objective lens. Then, integrating the developed optical detection method with swab sampling to achieve to detect bacterial cells loading on stainless-steel surfaces. Using Salmonella enterica (SE1045) and Escherichia coli as model bacterial cells, we achieved a capture efficiency of up to 76.0 % for SE1045 cells and 81.1 % for E. coli cells at Log 3 CFU/mL upon the optimized conditions. Our assay showed good linear relationship between the concentrations of bacterial cells with the cell counting in images with the limit of detection (LOD) of Log 3 CFU/mL for both SE1045 and E. coli cells. A further increase in sensitivity in detecting E. coli cells was achieved through a heat treatment, enabling the LOD to be pushed as low as Log 2 CFU/mL. Furthermore, successful application was observed in assessing bacterial contamination on stainless-steel surface following integrating with swab collection, achieving a recovery rate of approximately 70 % suggests future prospects for evaluating the cleanliness of surfaces. The entire process was completed within around 2 hours, with a cost of merely 2 dollars per sample. Given a standard light microscope cost around 250 dollars, our developed method has shown great potential in practical industrial applications for bacterial contamination control on surfaces in low-resource settings.

en q-bio.QM
DOAJ Open Access 2023
Aktivitas Antiradikal Krim Ekstrak Tanaman Gonda (Sphenoclea zeylanica Gaertn) dengan Metode DPPH (1,1-diphenyl-2-picrylhydrazyl)

Ni Kadek Vinka Lionita, Ni Putu Wintariani, Dewi Puspita Apsari

Radikal bebas adalah suatu senyawa yang memicu proses penuaan dini. Dilakukan pengembangan sediaan krim ekstrak tanaman Gonda (Sphenoclea zeylanica Gaertn) yang mengandung zat aktif antioksidan yang mampu melawan radikal bebas. Tujuan dari penelitian ini adalah untuk mengetahui senyawa fitokimia ekstrak etanol 96% tanaman Gonda (Sphenoclea zeylanica Gaertn), melihat sifat fisika kimia krim ekstrak tanaman Gonda (Sphenoclea zeylanica Gaertn), serta potensinya sebagai antioksidan melalui uji antiradikal dengan metode DPPH. Penelitian ini merupakan penelitian eksperimental dengan empat formula sediaan krim dan variasi konsentrasi ekstrak yang terdiri dari 0% (F0), 5% (F1), 10% (F2), 15% (F3). Evaluasi sifat fisika kimia yang dilakukan adalah uji organoleptis, uji homogenitas, uji daya sebar, uji viskositas, uji daya lekat, dan uji pH, serta aktivitas antiradikal yang diuji dengan menggunakan metode DPPH. Hasil penelitian menunjukkan ekstrak etanol 96% tanaman Gonda (Sphenoclea zeylanica Gaertn) positif mengandung flavonoid, saponin, tanin, steroid, dan alkaloid. Krim ekstrak tanaman Gonda (Sphenoclea zeylanica Gaertn) memiliki sifat fisika kimia yang baik berdasarkan uji evaluasi krim serta menunjukkan aktivitas antiradikal rata-rata F0 yaitu 596,08 dengan kategori sangat lemah, F1 (5%) yaitu 95,32 dengan kategori kuat, F2 (10%) yaitu 64,58 dengan kategori kuat, F3 (15%) yaitu 40,96 dengan kategori sangat kuat, dan rata-rata kontrol positif yaitu 22,74 dengan kategori sangat kuat. Ekstrak etanol 96% tanaman gonda sebagai bahan aktif dalam sediaan krim berpotensi dikembangkan menjadi antioksidan topikal dan perlu diteliti lebih lanjut aktivitas antioksidannya secara in vitro maupun in vivo.

Pharmacy and materia medica
arXiv Open Access 2023
Exploring contrast generalisation in deep learning-based brain MRI-to-CT synthesis

Lotte Nijskens, Cornelis, AT van den Berg et al.

Background: Synthetic computed tomography (sCT) has been proposed and increasingly clinically adopted to enable magnetic resonance imaging (MRI)-based radiotherapy. Deep learning (DL) has recently demonstrated the ability to generate accurate sCT from fixed MRI acquisitions. However, MRI protocols may change over time or differ between centres resulting in low-quality sCT due to poor model generalisation. Purpose: investigating domain randomisation (DR) to increase the generalisation of a DL model for brain sCT generation. Methods: CT and corresponding T1-weighted MRI with/without contrast, T2-weighted, and FLAIR MRI from 95 patients undergoing RT were collected, considering FLAIR the unseen sequence where to investigate generalisation. A ``Baseline'' generative adversarial network was trained with/without the FLAIR sequence to test how a model performs without DR. Image similarity and accuracy of sCT-based dose plans were assessed against CT to select the best-performing DR approach against the Baseline. Results: The Baseline model had the poorest performance on FLAIR, with mean absolute error (MAE)=106$\pm$20.7 HU (mean$\pmσ$). Performance on FLAIR significantly improved for the DR model with MAE=99.0$\pm$14.9 HU, but still inferior to the performance of the Baseline+FLAIR model (MAE=72.6$\pm$10.1 HU). Similarly, an improvement in $γ$-pass rate was obtained for DR vs Baseline. Conclusions: DR improved image similarity and dose accuracy on the unseen sequence compared to training only on acquired MRI. DR makes the model more robust, reducing the need for re-training when applying a model on sequences unseen and unavailable for retraining.

en physics.med-ph, cs.AI
arXiv Open Access 2023
The 4D Camera: an 87 kHz direct electron detector for scanning/transmission electron microscopy

Peter Ercius, Ian J. Johnson, Philipp Pelz et al.

We describe the development, operation, and application of the 4D Camera -- a 576 by 576 pixel active pixel sensor for scanning/transmission electron microscopy which operates at 87,000 Hz. The detector generates data at approximately 480 Gbit/s which is captured by dedicated receiver computers with a parallelized software infrastructure that has been implemented to process the resulting 10 - 700 Gigabyte-sized raw datasets. The back illuminated detector provides the ability to detect single electron events at accelerating voltages from 30 - 300 keV. Through electron counting, the resulting sparse data sets are reduced in size by 10 - 300x compared to the raw data, and open-source sparsity-based processing algorithms offer rapid data analysis. The high frame rate allows for large and complex 4D-STEM experiments to be accomplished with typical STEM scanning parameters.

en physics.ins-det, cond-mat.mtrl-sci
DOAJ Open Access 2022
In Vitro and In Vivo Effect of pH-Sensitive PLGA-TPGS-Based Hybrid Nanoparticles Loaded with Doxorubicin for Breast Cancer Therapy

Renata S. Fernandes, Raquel Gregório Arribada, Juliana O. Silva et al.

Doxorubicin (DOX) is an antineoplastic agent clinically employed for treating breast cancer patients. Despite its effectiveness, its inherent adverse toxic side effects often limit its clinical application. To overcome these drawbacks, lipid–polymer hybrid nanoparticles (LPNP) arise as promising nanoplatforms that combine the advantages of both liposomes and polymeric nanoparticles into a single delivery system. Alpha-tocopherol succinate (TS) is a derivative of vitamin E that shows potent anticancer mechanisms, and it is an interesting approach as adjuvant. In this study, we designed a pH-sensitive PLGA-polymer-core/TPGS-lipid-shell hybrid nanoparticle, loaded with DOX and TS (LPNP_TS-DOX). Nanoparticles were physicochemically and morphologically characterized. Cytotoxicity studies, migration assay, and cellular uptake were performed in 4T1, MCF-7, and MDA-MB-231 cell lines. Antitumor activity in vivo was evaluated in 4T1 breast tumor-bearing mice. In vitro studies showed a significant reduction in cell viability, cell migration, and an increase in cellular uptake for the 4T1 cell line compared to free DOX. In vivo antitumor activity showed that LPNP-TS-DOX was more effective in controlling tumor growth than other treatments. The high cellular internalization and the pH-triggered payload release of DOX lead to the increased accumulation of the drugs in the tumor area, along with the synergic combination with TS, culminating in greater antitumor efficacy. These data support LPNP-TS-DOX as a promising drug delivery system for breast cancer treatment.

Pharmacy and materia medica
arXiv Open Access 2022
Reconfigurable Reservoir Computing in a Magnetic Metamaterial

Ian Vidamour, Charles Swindells, Guru Venkat et al.

In-materia reservoir computing (RC) leverages the intrinsic physical responses of functional materials to perform complex computational tasks. Magnetic metamaterials are exciting candidates for RC due to their huge state space, nonlinear emergent dynamics, and non-volatile memory. However, to be suitable for a broad range of tasks, the material system is required to exhibit a broad range of properties, and isolating these behaviours experimentally can often prove difficult. By using an electrically accessible device consisting of an array of interconnected magnetic nanorings -- a system shown to exhibit complex emergent dynamics -- here we show how reconfiguring the reservoir architecture allows exploitation of different aspects the system's dynamical behaviours. This is evidenced through state-of-the-art performance in diverse benchmark tasks with very different computational requirements, highlighting the additional computational configurability that can be obtained by altering the input/output architecture around the material system.

en cond-mat.mes-hall
S2 Open Access 2021
Standardization of Homoeopathic Mother Tincture of Strychnous nux vomica with the help of High-Performance Thin Layer Chromatography and correlation of its alkaloid markers with its Toxicological action

D. Sharma, P. Aphale, Vineet Sinnarkar et al.

Background: Chromatography is one of the important laboratory technique in which the components of a mixture are separated on an adsorbent in order to analyze, identify, purify and quantify a mixture. Thin Layer Chromatography (TLC)is used to support the identity of a compound in a mixture when the Rf of a compound is compared with the Rf of a known compound. High Performance Thin Layer Chromatography is a sophisticated and automated form of Thin Layer Chromatography (TLC). The procedure simultaneously processes the sample and standard that results in better analytical precision and accuracy at a faster pace. Pharmacological/ Toxicological action of Nux Vomica is because of its active principles present in the seeds namely strychnine, brucine etc. This research paper aims to corelate the active principles present in Nux Vomica with the toxicological action of the same. Materials and Methods: 1. Standard Nux Vomica mother tincture was tested for its alkaloid markers and its correlation with the toxicological action was studied. 2. Analysis of the mother tincture was done using High Performance Thin Layer Chromatography. 3. Stationary phase consisted of TLC Aluminium sheets with silica gel 60 F253 pre-coated layer (20cm x 10cm), thickness-0.2mm, no. of tracks-18, band length-6mm. 4. Mobile Phase consisted of Chloroform: Methanol (9.5:0.5). 5. The plate was developed in developing chamber and observed under U.V. Light. Results: Colours seen on the HPTLC Plates of samples are greenwhich corresponds to strychnine, dark blue which corresponds to brucine, orange to alkaloids fluorescent green to sterols and pink to fatty acids which are evident on the chromatogram. Conclusion: Therapeutic action of Nux Vomica as noted in Homoeopathic Materia Medica is because of the active principles like strychnine, brucine, alkaloids, sterols, fatty acids present in it which is evident from the chromatogram.

2 sitasi en Chemistry
DOAJ Open Access 2021
Repurposing of the ALK Inhibitor Crizotinib for Acute Leukemia and Multiple Myeloma Cells

Joelle C. Boulos, Mohamed E. M. Saeed, Manik Chatterjee et al.

Crizotinib was a first generation of ALK tyrosine kinase inhibitor approved for the treatment of <i>ALK</i>-positive non-small-cell lung carcinoma (NSCLC) patients. COMPARE and cluster analyses of transcriptomic data of the NCI cell line panel indicated that genes with different cellular functions regulated the sensitivity or resistance of cancer cells to crizotinib. Transcription factor binding motif analyses in gene promoters divulged two transcription factors possibly regulating the expression of these genes, i.e., RXRA and GATA1, which are important for leukemia and erythroid development, respectively. COMPARE analyses also implied that cell lines of various cancer types displayed varying degrees of sensitivity to crizotinib. Unexpectedly, leukemia but not lung cancer cells were the most sensitive cells among the different types of NCI cancer cell lines. Re-examining this result in another panel of cell lines indeed revealed that crizotinib exhibited potent cytotoxicity towards acute myeloid leukemia and multiple myeloma cells. P-glycoprotein-overexpressing CEM/ADR5000 leukemia cells were cross-resistant to crizotinib. NCI-H929 multiple myeloma cells were the most sensitive cells. Hence, we evaluated the mode of action of crizotinib on these cells. Although crizotinib is a TKI, it showed highest correlation rates with DNA topoisomerase II inhibitors and tubulin inhibitors. The altered gene expression profiles after crizotinib treatment predicted several networks, where <i>TOP2A</i> and genes related to cell cycle were downregulated. Cell cycle analyses showed that cells incubated with crizotinib for 24 h accumulated in the G<sub>2</sub>M phase. Crizotinib also increased the number of p-H3(Ser10)-positive NCI-H929 cells illustrating crizotinib’s ability to prevent mitotic exit. However, cells accumulated in the sub-G<sub>0</sub>G<sub>1</sub> fraction with longer incubation periods, indicating apoptosis induction. Additionally, crizotinib disassembled the tubulin network of U2OS cells expressing an α-tubulin-GFP fusion protein, preventing migration of cancer cells. This result was verified by in vitro tubulin polymerization assays. In silico molecular docking also revealed a strong binding affinity of crizotinib to the colchicine and <i>Vinca</i> alkaloid binding sites. Taken together, these results demonstrate that crizotinib destabilized microtubules. Additionally, the decatenation assay showed that crizotinib partwise inhibited the catalytic activity of DNA topoisomerase II. In conclusion, crizotinib exerted kinase-independent cytotoxic effects through the dual inhibition of tubulin polymerization and topoisomerase II and might be used to treat not only NSCLC but also multiple myeloma.

Medicine, Pharmacy and materia medica
arXiv Open Access 2021
The Evolution of Materials Acceleration Platforms -- Towards the Laboratory of the Future with AMANDA

Jerrit Wagner, Christian G. Berger, Xiaoyan Du et al.

The development of complex functional materials poses a multi-objective optimization problem in a large multidimensional parameter space. Solving it requires reproducible, user independent laboratory work and intelligent preselection of experiments. However, experimental materials science is a field where manual routines are still predominant, although other domains like pharmacy or chemistry have long used robotics and automation. As the number of publications on Materials Acceleration Platforms (MAPs) increases steadily, we review selected systems and fit them into the stages of a general material development process to examine the evolution of MAPs. Subsequently we present our approach to laboratory automation in materials science. We introduce AMANDA (Autonomous Materials and Device Application Platform), a generic platform for distributed materials research comprising a self-developed software backbone and several MAPs. One of them, LineOne (L1), is specifically designed to produce and characterize solution processed thin-film devices like organic solar cells (OSC). It is designed to perform precise closed-loop screenings of up to 272 device variations per day yet allows further upscaling. Each individual solar cell is fully characterized and all process steps are comprehensively documented. We want to demonstrate the capabilities of AMANDA L1 with OSCs based on PM6:Y6 with 13.7% efficiency when processed in air. Further we discuss challenges and opportunities of highly automated research platforms and elaborate on the future integration of additional techniques, methods and algorithms in order to advance to fully autonomous self-optimizing systems - a paradigm shift in functional materials development leading to the laboratory of the future.

en cond-mat.mtrl-sci, physics.app-ph
DOAJ Open Access 2020
In Vitro Performance and Chemical Stability of Lipid-Based Formulations Encapsulated in a Mesoporous Magnesium Carbonate Carrier

Caroline Alvebratt, Tahnee J. Dening, Michelle Åhlén et al.

Lipid-based formulations can circumvent the low aqueous solubility of problematic drug compounds and increase their oral absorption. As these formulations are often physically unstable and costly to manufacture, solidification has been suggested as a way to minimize these issues. This study evaluated the physicochemical stability and in vitro performance of lipid-loaded mesoporous magnesium carbonate (MMC) particles with an average pore size of 20 nm. A medium chain lipid was loaded onto the MMC carrier via physical adsorption. A modified in vitro lipolysis setup was then used to study lipid release and digestion with <sup>1</sup>H nuclear magnetic resonance spectroscopy. The lipid loading efficiency with different solidification techniques was also evaluated. The MMC, unlike more commonly used porous silicate carriers, dissolved during the lipolysis assay, providing a rapid release of encapsulated lipids into solution. The digestion of the dispersed lipid-loaded MMC therefore resembled that of a coarse dispersion of the lipid. The stability data demonstrated minor degradation of the lipid within the pores of the MMC particles, but storage for three months did not reveal extensive degradation. To conclude, lipids can be adsorbed onto MMC, creating a solid powder from which the lipid is readily released into the solution during in vitro digestion. The chemical stability of the formulation does however merit further attention.

Pharmacy and materia medica
S2 Open Access 2020
Special Issue: Nanomedicine: Therapeutic Applications

Xue Xue, Xing-jie Liang

Nanomedicine is considered to be one of the most promising technologies of the 21st century and has broadly developed as the application of nanotechnology to medicine. The therapeutic applications of nanomedicine have increased exponentially to offer impressive options for various health and medicinal issues in recent years. Many different systems and strategies of considerable potential for enabling more effective and less toxic therapeutic interventions have been investigated in the nanomedicine field with significant efforts and progress. In this issue of Advanced Therapeutics, we are proud to present these distinguish articles, which integrate the strengths of scientists from life science, chemistry, medicine, and pharmacy fields, to comprehensively introduce the development of compositions, syntheses, and biomedical applications of nanomaterials for disease therapy. We are deeply appreciative of the opportunity afforded by Advanced Therapeutics to organize this special issue. The special issue, featuring 5 reviews, 2 full papers, 1 communication, and 1 progress report, convers a broad spectrum of the therapeutic nanomaterials including biological materials, catalytical materials, photonic/optical materials, as well as the advanced applications of modern organic/inorganic hybrid materials. The guest editors of this special issue are honored by the support given by the contributors, with particular acknowledgement to Prof. Alfonso E. Garcia-Bennett fromMacquarie University, Prof. Yaping Li and Zhiwen Zhang from Shanghai Institute of Materia Medica, Chinese Academy of Sciences the, Prof. Xiaogang Qu from Changchun Institute of Applied Chemistry, Chinese Academy

en Engineering
S2 Open Access 2019
Ethnopharmacological study of Sephardic remedies in the 19th century: The "Livro de Milizinas".

D. Rivera, Mauricio López Acosta, A. Verde et al.

ETHNOPHARMACOLOGICAL RELEVANCE The Sephardic or Judeo-Spanish communities kept a cultural heritage extremely relevant which is recognizable through the peculiar form of their language and practices. Medicine was one of the main professional activities among Jews of Spain before their expulsion in 1492. We expected to find ingredients and recipes in the Sephardic traditional medicine related to classical medicine and to modern ethnopharmacology of Spain, but also influenced by the host countries. Recipes for specific diseases could be compared with modern ethnopharmacology. Although the basic language of the recipes is Judeo-Spanish, it presents local variants and names which are not only dialectal Spanish, but also Turkish, Hebrew or Bosnian. METHODS The main source of information for Sephardic folk medicine are the specimens of the "Livro de Milizinas" printed in Thessaloniki and Smyrna (Izmir) during the 19th century. Others are some documents on pharmacy conserved in Bosnia associated to the Papo family of Sephardic Aktars or Attars (Ottoman herbalists) and the oral tradition in the Sephardic communities of Asia, Europe and the Americas. In order to analyze these formularies, we have studied the recipes in eleven different sources systematized in an Excel® 2010 book. We focused on formulas that are not merely rituals instead contain specific ingredients and pathologies. Specific dictionaries were generated in Excel® 2010, to standardize names of ingredients and pathologies. RESULTS In the 502 complete recipes and variants studied, 107 pathologies and 154 different ingredients appear. Among ingredients, 93 are plants, 38 animals and 23 mineral substances. The most common pathologies in the recipes correspond to infectious diseases, headache, epistaxis, parasites and the "espanto". These ingredients received 397 different vernacular names, being prevalent those in Spanish (303) followed by those in Turkish. Preparations recorded are simple, easily made at home, not requiring special tools or hardware. In studies dated 1845 in Bulgaria the forms of preparation and administration are similar. Topic preparations externally applied are prevalent in numbers doubling the oral administration on the contrary of modern ethnopharmacology studies in Thessaloniki where dominate internal uses over external ones. The books of medicines of Smyrna and Thessaloniki are very similar, if not almost identical. The "Livro de Milizinas" constitute a peculiar Sephardic text within the Ottoman style of medicine. The proximity in the analyses with Ottoman sources (Ottoman pharmacopoeias, Turkish Aktar shops and Medieval Cairo Jewish pharmacopoeia) is due to the high proportion of ingredients in common. After excluding animal and mineral ingredients of the analyses, modern ethnobotanical records from Greece and Turkey appear closer to the Sephardic main sources. The rest of Sephardic sources with notably smaller lists of ingredients represent fragments of mostly oral transmitted tradition and treat pathologies such as evil eye or "espanto". The recipes of the Sephardic of Bosnia comprise pathologies such as plague, cholera, typhus or gastroenteritis. Ingredients, largely of plant origin, to 93, are still in use in phytotherapy and/or local medical-pharmaceutical ethnobotany in Turkey or Greece. CONCLUSIONS The Sephardic materia medica presented in the "Livro de Milizinas" is eclectic, adapted to an urban environment and to the prevalent pathologies of the second half of the 19th century, within the main cultural framework of the Ottoman Empire but with peculiarities characteristic of Sephardic Culture. These can be traced back to the period immediately after the expulsion of Sephardic from Spain. Their relationships with other modern sources are scarce, even in terms of pathologies.

3 sitasi en Medicine, History
DOAJ Open Access 2019
Uso do omeprazol: estudo descritivo de pacientes idosos de uma Unidade de Saúde da Família (USF) de Ribeirão Preto, SP, Brasil

Jean Mozart de LIMA, Amaury Lelis DAL FABBRO, André Rodrigues FUNAYAMA

O primeiro inibidor da bomba de prótons (IBP) comercializado no mundo foi o omeprazol. É hoje amplamente prescrito na Atenção Básica brasileira. Estudos indicam que o uso a longo prazo pode estar relacionado a efeitos adversos importantes na qualidade de vida do paciente. Assim, o objetivo foi avaliar a prevalência e o perfil clínico de pacientes idosos em uso de omeprazol em uma Unidade de Saúde da Família (USF). Foi realizado um estudo transversal descritivo em que foram avaliados pacientes idosos, usuários de uma USF. Foram incluídos no estudo 100 pacientes idosos. Desses, 35 faziam uso do omeprazol, sendo 10 do sexo masculino e 25 do sexo feminino. A dose de 20 mg diária foi encontrada em 68,6% dos usuários, 91,4% tem prescrição por mais de doze meses e 51,4% não possuíam registro do motivo de uso do omeprazol, 17,1% tinham descrito epigastralgia como justificativa de uso. O omeprazol pode estar sendo prescrito sem uma clara indicação de uso e por tempo de tratamento prolongado, colaborando para o uso inadequado desse medicamento.

Medicine, Pharmacy and materia medica

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