scholarly journals P11.44 Conception of a promising future therapy: Drug loaded-microbubbles against glioblastoma

2019 ◽  
Vol 21 (Supplement_3) ◽  
pp. iii53-iii53
Author(s):  
E Schulz ◽  
V Mawamba ◽  
V Sturm ◽  
R Ernestus ◽  
U Schatzschneider ◽  
...  
Keyword(s):  
Real Time ◽  
Molecular Size ◽  
Chemotherapeutic Agents ◽  
New Drugs ◽  
Toxic Effects ◽  
Side Chains ◽  
Local Concentration ◽  
Tumor Site ◽  
Proliferation Assay ◽  
Reference Drug

Abstract BACKGROUND Major obstacles for an effective chemotherapy of glioblastomas (GBM) are the blood-brain-barrier (BBB) and serious systemic side effects of the cytotoxic drugs. A new promising strategy could be the delivery of microbubbles, encapsulating the chemotherapeutics, across the BBB to the tumor site. This will shield the drug from detrimental systemic effects. Low intensity focused ultrasound (LIFU) is able to open the BBB and triggers targeted release of the drugs within the tumor. First data on the synthesis of microbubbles, specifically designed new drugs and the targeted rupture of microbubbles by LIFU are presented. MATERIAL AND METHODS Thin-film hydration of lipids was utilized to prepare microbubbles, which were tested for toxicity on the GBM cell lines GaMG, U87, U138 and U343. In addition these cells were treated with 6 platinum(II) and palladium(II) complexes conjugated to lipophilic side chains of different length (C1, C8, C10) for 72h. To evaluate cell viability and calculate EC50 values MTT assays and a real-time proliferation assay using the impedance-based xCELLigence DP-System were executed. RESULTS Microbubbles ≤ 2µm in diameter were synthesized and could be disintegrated by applying LIFU. Neither the intact bubbles nor the lipids alone had any toxic effects on the GBM cells. In contrast, all six drugs were highly effective with EC50 values far below those of Temozolomide (67µM) and in the range of the reference drug cisplatin (3µM). Especially the palladium(II) compound with the C1-chain displayed a very low EC50 value (<10µM), while the longer chains and the platinum(II) compounds were less effective (EC50 10–40µM). An early and concentration-dependent onset of the cytotoxic effect of drugs with C1 and C8 side chains was revealed in the real time proliferation assay. CONCLUSION All components for a new microbubble-based therapeutic strategy are in place. Microbubbles were synthesized without having toxic effects in cell culture. New highly potent palladium(II) and platinum(II) compounds with low EC50 values were developed. The next step will be their encapsulation into the microbubbles via their lipophilic side chains to develop an effective drug-delivery system for the treatment of GBM in combination with LIFU. This will allow increasing the local concentration of chemotherapeutic agents at the tumor site, irrespectively of their molecular size and BBB penetration capacity.

scholarly journals Antimicrobial, Antioxidant, Anti-Acetylcholinesterase, Antidiabetic, and Pharmacokinetic Properties of Carum carvi L. and Coriandrum sativum L. Essential Oils Alone and in Combination

Molecules ◽  
2021 ◽  
Vol 26 (12) ◽  
pp. 3625
Author(s):  
Hafedh Hajlaoui ◽  
Soumaya Arraouadi ◽  
Emira Noumi ◽  
Kaïss Aouadi ◽  
Mohd Adnan ◽  
...  
Keyword(s):  
Essential Oils ◽  
Coriandrum Sativum ◽  
New Drugs ◽  
Antidiabetic Activity ◽  
Pharmacokinetic Analysis ◽  
Bacterial Strains ◽  
Standard Drug ◽  
Reference Drug ◽  
Antioxidant Power ◽  
Carum Carvi

Herbs and spices have been used since antiquity for their nutritional and health properties, as well as in traditional remedies for the prevention and treatment of many diseases. Therefore, this study aims to perform a chemical analysis of both essential oils (EOs) from the seeds of Carum carvi (C. carvi) and Coriandrum sativum (C. sativum) and evaluate their antioxidant, antimicrobial, anti-acetylcholinesterase, and antidiabetic activities alone and in combination. Results showed that the EOs mainly constitute monoterpenes with γ-terpinene (31.03%), β-pinene (18.77%), p-cymene (17.16%), and carvone (12.20%) being the major components present in C. carvi EO and linalool (76.41%), γ-terpinene (5.35%), and α-pinene (4.44%) in C. sativum EO. In comparison to standards, statistical analysis revealed that C. carvi EO showed high and significantly different (p < 0.05) antioxidant activity than C. sativum EO, but lower than the mixture. Moreover, the mixture exhibited two-times greater ferric ion reducing antioxidant power (FRAP) (IC50 = 11.33 ± 1.53 mg/mL) and equipotent chelating power (IC50 = 31.33 ± 0.47 mg/mL) than the corresponding references, and also potent activity against 2,2-diphenyl-1-picrylhydrazyl (DPPH) (IC50 = 19.00 ± 1.00 mg/mL), β-carotene (IC50 = 11.16 ± 0.84 mg/mL), and superoxide anion (IC50 = 10.33 ± 0.58 mg/mL) assays. Antimicrobial data revealed that single and mixture EOs were active against a panel of pathogenic microorganisms, and the mixture had the ability to kill more bacterial strains than each EO alone. Additionally, the anti-acetylcholinesterase and α-glucosidase inhibitory effect have been studied for the first time, highlighting the high inhibition effect of AChE by C. carvi (IC50 = 0.82 ± 0.05 mg/mL), and especially by C. sativum (IC50 = 0.68 ± 0.03 mg/mL), as well as the mixture (IC50 = 0.63 ± 0.02 mg/mL) compared to the reference drug, which are insignificantly different (p > 0.05). A high and equipotent antidiabetic activity was observed for the mixture (IC50 = 0.75 ± 0.15 mg/mL) when compared to the standard drug, acarbose, which is about nine times higher than each EO alone. Furthermore, pharmacokinetic analysis provides some useful insights into designing new drugs with favorable drug likeness and safety profiles based on a C. carvi and C. sativum EO mixture. In summary, the results of this study revealed that the combination of these EOs may be recommended for further food, therapeutic, and pharmaceutical applications, and can be utilized as medicine to inhibit several diseases.

scholarly journals Recent Advances in Application of Biosensors in Tissue Engineering

2014 ◽  
Vol 2014 ◽  
pp. 1-18 ◽  
Author(s):  
Anwarul Hasan ◽  
Md Nurunnabi ◽  
Mahboob Morshed ◽  
Arghya Paul ◽  
Alessandro Polini ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Cell Culture ◽  
Small Molecules ◽  
Real Time ◽  
Inflammatory Cytokines ◽  
Serum Proteins ◽  
Molecular Size ◽  
Medical Diagnostics ◽  
Alpha Fetoprotein ◽  
Pharmaceutical Industries

Biosensors research is a fast growing field in which tens of thousands of papers have been published over the years, and the industry is now worth billions of dollars. The biosensor products have found their applications in numerous industries including food and beverages, agricultural, environmental, medical diagnostics, and pharmaceutical industries and many more. Even though numerous biosensors have been developed for detection of proteins, peptides, enzymes, and numerous other biomolecules for diverse applications, their applications in tissue engineering have remained limited. In recent years, there has been a growing interest in application of novel biosensors in cell culture and tissue engineering, for example, real-time detection of small molecules such as glucose, lactose, and H2O2as well as serum proteins of large molecular size, such as albumin and alpha-fetoprotein, and inflammatory cytokines, such as IFN-g and TNF-α. In this review, we provide an overview of the recent advancements in biosensors for tissue engineering applications.

scholarly journals The Effect of Antimicrobial Drugs Tylocolinum, Tetragold and Cidisept-o on Escherichia coli Ultrastructure

2013 ◽  
Vol 2 (3) ◽  
pp. 65
Author(s):  
A. G. Shakhov ◽  
D. V. Fedosov ◽  
L. Y. Sashnina ◽  
O. V. Kazimirov
Keyword(s):  
Escherichia Coli ◽  
Bacterial Infections ◽  
Antimicrobial Agents ◽  
Water Solution ◽  
Uranyl Acetate ◽  
Chemotherapeutic Agents ◽  
Control Culture ◽  
New Drugs ◽  
Ultrastructural Changes ◽  
The Impact

<p>As a result of wide antibiotics, sulfonamides and other antimicrobial agents usage for the therapy of the animals with the bacterial infections caused by various causative agents including <em>Escherichia coli</em>, many microorganisms gained resistance to the chemotherapeutic agents. New combined drugs are being worked out during recent years, the components of which have various influence mechanisms on the bacterial cell that helps to provide resistance forming control. The results of the researches of the new antimicrobial agents, containing antibiotics in their composition, and non-antibiotic agent influence on the ultrastructure of <em>Escherichia coli</em> are represented in this study.</p> <p>5-hour <em>Escherichia coli 866</em> culture was processed by the drugs of the minimum bactericidal (Tylocolinum-0.39 µg/ml, Tetragold-6.25 µg/ml, Cidisept-o-25 µg/ml) and 4-time concentrations during 3 hours. Samples and control culture (without drugs) were fixed by the 2.5% glutaricdialdehyde on the s-Collidine Buffer, dehydrated in the ethanol with rising concentration, filled in epoxies. Ultrathin slices were stained by 2% water solution of uranyl acetate and lead citrate for 10 minutes. Then they were examined with the use of the electron microscope JEM-100 CX II by JEOL.</p> <p>The research showed deep ultrastructural changes in <em>Escherichia coli</em> cells under the antimicrobial agent influence determined by synergistic effect of combined Tylocolinum and Tetragold drugs components, possessing various bacteria influencing mechanisms, and aldehyde that is a component of Cidisept-o.</p> The electron microscopy usage allows to get unique information about the impact consequences of the traditional improved drugs and new drugs with antimicrobial activity on the bacterial infectious agents.

scholarly journals Recent Applications of Retro-Inverso Peptides

2021 ◽  
Vol 22 (16) ◽  
pp. 8677
Author(s):  
Nunzianna Doti ◽  
Mario Mardirossian ◽  
Annamaria Sandomenico ◽  
Menotti Ruvo ◽  
Andrea Caporale
Keyword(s):  
Amino Acids ◽  
Neurodegenerative Diseases ◽  
De Novo ◽  
3D Structure ◽  
New Drugs ◽  
Side Chains ◽  
Pros And Cons ◽  
Endogenous Proteases ◽  
Natural Amino Acids ◽  
Poor Stability

Natural and de novo designed peptides are gaining an ever-growing interest as drugs against several diseases. Their use is however limited by the intrinsic low bioavailability and poor stability. To overcome these issues retro-inverso analogues have been investigated for decades as more stable surrogates of peptides composed of natural amino acids. Retro-inverso peptides possess reversed sequences and chirality compared to the parent molecules maintaining at the same time an identical array of side chains and in some cases similar structure. The inverted chirality renders them less prone to degradation by endogenous proteases conferring enhanced half-lives and an increased potential as new drugs. However, given their general incapability to adopt the 3D structure of the parent peptides their application should be careful evaluated and investigated case by case. Here, we review the application of retro-inverso peptides in anticancer therapies, in immunology, in neurodegenerative diseases, and as antimicrobials, analyzing pros and cons of this interesting subclass of molecules.

scholarly journals Chemotherapy-Associated Pulmonary Toxicity—Case Series from a Single Center

2021 ◽  
Author(s):  
Tilak TVSVGK ◽  
Ajay Handa ◽  
Kishore Kumar ◽  
Deepti Mutreja ◽  
Shankar Subramanian
Keyword(s):  
Observational Study ◽  
Pulmonary Toxicity ◽  
Imaging Finding ◽  
Tertiary Care ◽  
Case Series ◽  
Fiberoptic Bronchoscopy ◽  
Chemotherapeutic Agents ◽  
New Drugs ◽  
Care Hospital ◽  
Persistent Symptoms

Abstract Background Pulmonary toxicity due to chemotherapeutic agents can occur with many established and new drugs. Strong clinical suspicion is important as the clinical presentation is usually with nonspecific symptoms like cough, dyspnea, fever, and pulmonary infiltrates. Timely discontinuation of the offending agent alone can improve the condition. Methods A prospective observational study on patients receiving chemotherapy at an 800-bedded tertiary care hospital was performed from 2014 to 2016. Consecutive patients on chemotherapy, presenting with nonresolving respiratory symptoms were evaluated with contrast-enhanced computerized tomography of chest, diffusion lung capacity for carbon monoxide (DLCO), fiberoptic bronchoscopy with lavage, and biopsy, after excluding all causes for pulmonary infections. Descriptive data has been depicted. Results A total of 18 patients were evaluated for persistent symptoms of dry cough, dyspnea, and fever among 624 who received chemotherapy during the study period. Ground-glass opacities on high-resolution CT was the most common imaging finding, others being patchy subpleural consolidation and pleural effusion. Lymphocyte-predominant bronchoalveolar lavage was detected in nine. Eight of the 15 patients who underwent DLCO, had abnormal results. Seven had significant histopathological findings on bronchoscopic lung biopsy, which revealed organizing pneumonia as the most common pattern. Paclitaxel, fluorouracil, gemcitabine, and tyrosine kinase inhibitors were the common culprit drugs. Discontinuation alone of the culprit drug was effective in 15 and 3 needed oral corticosteroids for relief of symptoms. None of the patients died due to the toxicity. Conclusion An incidence of 2.8% for chemotherapy-induced lung injury was seen in our observational study of 3 years, with parenchymal, interstitial, and pleural involvement due to various chemotherapeutic agents. Oral steroids maybe required in a subset of patients not responding to discontinuation of the culprit agent.

Minimal Residual Disease in Hematologic Disorders

1999 ◽  
Vol 123 (11) ◽  
pp. 1030-1034
Author(s):  
Stefan Faderl ◽  
Razelle Kurzrock ◽  
Zeev Estrov
Keyword(s):  
Minimal Residual Disease ◽  
Residual Disease ◽  
Chemotherapeutic Agents ◽  
New Drugs ◽  
Myelogenous Leukemia ◽  
Therapeutic Success ◽  
Acute Leukemias ◽  
Hematologic Disorders ◽  
Kinetics Of ◽  
Minimal Residual

Abstract In almost no other area of medical oncology has the introduction of new drugs, combinations of chemotherapeutic agents, and novel biologic treatments caused such dramatic responses as it has in the treatment of malignant hematologic disorders. However, despite some therapeutic success, many patients relapse and die from recurrence of their disease. The implications of minimal residual disease (MRD), a term referring to disease that is undetectable by conventional morphologic methods, have therefore attracted increasing attention in recent years. New and powerful laboratory tools such as polymerase chain reaction assays have extraordinary sensitivity and provide exciting new insights into the detection, nature, quantification, and kinetics of MRD. This article summarizes methods used in the identification of MRD and its importance as exemplified in the case of acute leukemias and chronic myelogenous leukemia.

scholarly journals Applications of Nanomaterials for Theranostics of Melanoma

2020 ◽  
Vol 1 (1) ◽  
pp. 39-55
Author(s):  
Guanqiao Jin ◽  
Pohlee Cheah ◽  
Jing Qu ◽  
Lijuan Liu ◽  
Yongfeng Zhao
Keyword(s):  
Drug Delivery ◽  
Molecular Imaging ◽  
Early Diagnosis ◽  
Real Time ◽  
Treatment Plan ◽  
Chemotherapeutic Agents ◽  
The Body ◽  
Diagnostic Methods ◽  
Therapeutic Drug

Melanoma is an aggressive form of skin cancer with a very high mortality rate. Early diagnosis of the disease, the utilization of more potent pharmacological agents, and more effective drug delivery systems are essential to achieve an optimal treatment plan. The applications of nanotechnology to improve therapeutic efficacy and early diagnosis for melanoma treatment have received great interest among researchers and clinicians. In this review, we summarize the recent progress of utilizing various nanomaterials for theranostics of melanoma. The key importance of using nanomaterials for theranostics of melanoma is to improve efficacy and reduce side effects, ensuring safe implementation in clinical use. As opposed to conventional in vitro diagnostic methods, in vivo medical imaging technologies have the advantages of being a type of non-invasive, real-time monitoring. Several common nanoparticles, including ultrasmall superparamagnetic iron oxide nanoparticles, silica nanoparticles, and carbon-based nanoparticles, have been applied to deliver chemotherapeutic agents for the theranostics of melanoma. The application of nanomaterials for theranostics in molecular imaging (MRI, PET, US, OI, etc.) plays an important role in targeting drug delivery of melanoma, by monitoring the distribution site of the molecular imaging probe and the therapeutic drug in the body in real-time. Hence, it is worthwhile to anticipate the approval of these nanomaterials for theranostics in molecular imaging by the US Food and Drug Administration in clinical trials.

scholarly journals Novel and Stable Dual-Color IL-6 and IL-10 Reporters Derived from RAW 264.7 for Anti-Inflammation Screening of Natural Products

2019 ◽  
Vol 20 (18) ◽  
pp. 4620
Author(s):  
Papawee Saiki ◽  
Yasuhiro Kawano ◽  
Yoshihiro Nakajima ◽  
Leo J. L. D. Van Griensven ◽  
Koyomi Miyazaki
Keyword(s):  
Natural Products ◽  
Real Time ◽  
Inflammatory Disease ◽  
Chronic Inflammatory Disease ◽  
New Drugs ◽  
Raw 264.7 Cells ◽  
Raw 264.7 ◽  
Screening Assay ◽  
Dual Color ◽  
Ethanol Extracts

Our previous study suggested that the interleukin (IL)-6 and IL-10 could serve as good biomarkers for chronic inflammatory disease. We previously established an IL-6 and IL-10 reporters assay that could examine reporter activity along with the reference gene in LPS-induced RAW 264.7 cells. In this study, we described new and stable RAW 264.7 derived dual-color IL-6/gapdh and IL-10/gapdh reporters. This assay allowed us to easily determine relative IL-6 and IL-10 levels with 96-well plate within one step. We evaluated the relative IL-6 and IL-10 levels in the LPS-induced stable cells testing 52 natural products by real-time bioluminescence monitoring and time-point determination using a microplate luminometer. The relative IL-6 and IL-6/IL-10 values decreased by the crude ethanol extracts from nutmeg and by 1′S-1′-acetoxychavicol from greater galangal using real-time bioluminescence monitoring. At the same time, the relative IL-10 was induced. The relative IL-6 and IL-6/IL-10 decreased by crude ethanol extracts from nutmeg and 1′S-1′-acetoxychavicol acetate at 6 h. Only crude ethanol extract from nutmeg induced IL-10 at 6 h. We suggested that the use of these stable cells by real-time monitoring could serve as a screening assay for anti-inflammatory activity and may be used to discover new drugs against chronic inflammatory disease.

scholarly journals Zinc-binding structure of a catalytic amyloid from solid-state NMR

2017 ◽  
Vol 114 (24) ◽  
pp. 6191-6196 ◽  
Author(s):  
Myungwoon Lee ◽  
Tuo Wang ◽  
Olga V. Makhlynets ◽  
Yibing Wu ◽  
Nicholas F. Polizzi ◽  
...  
Keyword(s):  
Solid State ◽  
Solid State Nmr ◽  
Protein Misfolding ◽  
Molecular Size ◽  
Advanced Materials ◽  
Side Chains ◽  
Evolution Of Life ◽  
Water Activation ◽  
Catalytic Reactivity ◽  
Molecular Bases

Throughout biology, amyloids are key structures in both functional proteins and the end product of pathologic protein misfolding. Amyloids might also represent an early precursor in the evolution of life because of their small molecular size and their ability to self-purify and catalyze chemical reactions. They also provide attractive backbones for advanced materials. When β-strands of an amyloid are arranged parallel and in register, side chains from the same position of each chain align, facilitating metal chelation when the residues are good ligands such as histidine. High-resolution structures of metalloamyloids are needed to understand the molecular bases of metal–amyloid interactions. Here we combine solid-state NMR and structural bioinformatics to determine the structure of a zinc-bound metalloamyloid that catalyzes ester hydrolysis. The peptide forms amphiphilic parallel β-sheets that assemble into stacked bilayers with alternating hydrophobic and polar interfaces. The hydrophobic interface is stabilized by apolar side chains from adjacent sheets, whereas the hydrated polar interface houses the Zn2+-binding histidines with binding geometries unusual in proteins. Each Zn2+ has two bis-coordinated histidine ligands, which bridge adjacent strands to form an infinite metal–ligand chain along the fibril axis. A third histidine completes the protein ligand environment, leaving a free site on the Zn2+ for water activation. This structure defines a class of materials, which we call metal–peptide frameworks. The structure reveals a delicate interplay through which metal ions stabilize the amyloid structure, which in turn shapes the ligand geometry and catalytic reactivity of Zn2+.

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