scholarly journals The Development of Novel Organotin Anti-Tumor Drugs: Structure and Activity

1998 ◽  
Vol 5 (4) ◽  
pp. 179-188 ◽  
Author(s):  
Dick de Vos ◽  
Rudolph Willem ◽  
Marcel Gielen ◽  
Kyra E. van Wingerden ◽  
Kees Nooter
Keyword(s):  
Water Solubility ◽  
Solubility In Water ◽  
In Vivo Testing ◽  
Polar Substituents ◽  
Tumor Drugs ◽  
Separate Class ◽  
Structure And Activity ◽  
Very High

An overview of the development of anti-tumor organotin derivatives in selected classes of compounds is presented and discussed. High to very high in vitro activity has been found, sometimes equaling that of doxorubicin. Solubility in water is an important issue, dominating the in vivo testing of compounds with promising in vitro properties. The cytotoxicity of the compounds was increased by the presence of a bulky group, an active substituent or one or more polar substituents. Polar substituents may also improve the water solubility. Although organotin derivatives constitute a separate class of compounds, the comparison with cisplatin is inevitable. Among the observed toxicities, neurotoxicity, known from platinum cytostatics, and gastrointestinal toxicity, typical for many oncology drugs, have been detected. Further research to develop novel, useful organotin anti-tumor compounds should be carried out.

scholarly journals Gallium-68-Labelled Indocyanine Green as a Potential Liver Reserve Imaging Agent

2019 ◽  
Vol 2019 ◽  
pp. 1-8
Author(s):  
Yuxiao Xia ◽  
Li Zhang ◽  
Yanhong Zhao ◽  
Xiangdong Liu ◽  
Liang Cai ◽  
...  
Keyword(s):  
Indocyanine Green ◽  
Protein Binding ◽  
Plasma Protein Binding ◽  
Plasma Protein ◽  
Water Solubility ◽  
Time Points ◽  
Binding Rate ◽  
Very High

Objective. This work evaluated the potential of 68Ga-labelledNOTA-ICG (1,4,7-triazacyclononane-1,4,7-triacetic acid indocyanine green) for liver reserve imaging. Methods. To determine the optimal conditions for generating 68Ga-NOTA-ICG, various reaction parameters were implemented. Quality control analysis was performed using different chromatography techniques. The in vitro and in vivo stability was also measured at specific time points. The radioactivity ratio between n-octanol and water was determined to evaluate the water solubility of 68Ga-NOTA-ICG. The plasma-protein binding rate of the labelled compound was determined by the methanol method. The biodistribution and imaging findings were evaluated in normal animals at different time points after injection. A preliminary imaging evaluation was performed using an animal model of hepatic ischaemia-reperfusion injury, which was confirmed by pathology. Results. 68Ga-NOTA-ICG was prepared with very high radiochemical purity (>98%) by reacting at 90°C for 10 min at pH = 3.5∼4.0, with excellent stability in vivo and in vitro (>95% 3 h postpreparation). The in vitro plasma-protein binding rate of 68Ga-NOTA-ICG was 13.01 ± 0.7%, and it showed strong water solubility log P=−2.01±0.04. We found that in addition to excretion through the biliary tract and intestines, 68Ga-NOTA-ICG can be excreted through the urinary tract. The image quality of 68Ga-NOTA-ICG was very high; imaging agent retained in the area of liver injury could clearly be observed. Conclusion. This is the first report on a 68Ga-labelled NOTA-ICG fragment for liver reserve function studies. This complex has promise as a candidate agent for liver reserve imaging.

scholarly journals γ-Cyclodextrin Metal-Organic Framework as a Carrier to Deliver Triptolide for the Treatment of Hepatocellular Carcinoma

2020 ◽  
Author(s):  
Zhe Li ◽  
Gang Yang ◽  
Rong Wang ◽  
Yuanyuan Wang ◽  
Jing Wang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Water Solubility ◽  
Metal Organic Framework ◽  
Cell Internalization ◽  
The Poor ◽  
Metal Organic ◽  
Tumor Drugs ◽  
Organic Framework

Abstract Triptolide (TPL) has been employed to treat hepatocellular carcinoma (HCC). However, the poor water-solubility of TPL restrict its applications. Therefore, we prepared TPL loaded cyclodextrin-based metal-organic framework (TPL@CD-MOF) to improve the solubility and bioavailability of TPL, thus enhancing the anti-tumor effect on HCC. The BET surface and the pore size of TPL@CD-MOF were 1134.5 m2·g−1 and 1.6 nm, respectively. The results of XRD indicated that TPL in TPL@CD-MOF was encapsuled. TPL@CD-MOF showed a slower release than free TPL in vitro. Moreover, the CD-MOF improved the cell internalization and bioavailability of TPL. TPL@CD-MOF also showed higher anti-tumor efficacy in vitro and in vivo compared to free TPL. As a carrier, CD-MOF improved the solubility and bioavailability of TPL. In addition, TPL@CD-MOF exhibited improved anti-tumor effects in vitro and in vivo, indicating great potential as a carrier for insoluble anti-tumor drugs.

scholarly journals Antimicrobial Activity of Pregnenolone in vitro

2021 ◽  
pp. 61-67
Author(s):  
Teodora P. Popova ◽  
Ignat Ignatov ◽  
Toshka Petrova ◽  
Georgi Dinkov
Keyword(s):  
Inhibitory Activity ◽  
Water Solubility ◽  
Antimicrobial Effect ◽  
Bacterial Strains ◽  
Intracellular Space ◽  
Solubility In Water ◽  
E Coli ◽  
Antimicrobial Substances

The antimicrobial effect of pregnenolone on clinical and reference strains of Escherichia coli and Staphylococcus aureus was tested. Pregnenolone was found to have inhibitory activity against all tested bacterial strains. Slightly higher sensitivity is shown by the strains of S. aureus. When applied directly, pregnenolone has a weak antimicrobial effect due to its very low water solubility, as it is in oleose state because the formulation studied in this experiment contains tocopherol (a fat-soluble vitamin) as a co-solvent. When emulsified with lecithin, as well as with methanol, its solubility in water increases and penetrates over a longer distance in the agar around the points of its application. Applied as an emulsion, it shows significantly higher inhibitory activity against E. coli and S. aureus. Even the non-emulsified version should still be useful in vivo due to the fact that intracellular environments are much more lipophilic than serum, the target of most antimicrobial substances is the intracellular space, and non-emulsified pregnenolone has been shown to have very high intracellular uptake.

Effects of Heparin Oligosaccharides with High Affinity for Antithrombin III in Experimental Venous Thrombosis

1982 ◽  
Vol 47 (03) ◽  
pp. 244-248 ◽  
Author(s):  
D P Thomas ◽  
Rosemary E Merton ◽  
T W Barrowcliffe ◽  
L Thunberg ◽  
U Lindahl
Keyword(s):  
Antithrombin Iii ◽  
Specific Activity ◽  
High Specific Activity ◽  
Factor Xa ◽  
Blood Levels ◽  
Thrombin Time ◽  
High Affinity ◽  
Very High

SummaryThe in vitro and in vivo characteristics of two oligosaccharide heparin fragments have been compared to those of unfractionated mucosal heparin. A decasaccharide fragment had essentially no activity by APTT or calcium thrombin time assays in vitro, but possessed very high specific activity by anti-Factor Xa assays. When injected into rabbits at doses of up to 80 ¼g/kg, this fragment was relatively ineffective in impairing stasis thrombosis despite producing high blood levels by anti-Xa assays. A 16-18 monosaccharide fragment had even higher specific activity (almost 2000 iu/mg) by chromogenic substrate anti-Xa assay, with minimal activity by APTT. When injected in vivo, this fragment gave low blood levels by APTT, very high anti-Xa levels, and was more effective in preventing thrombosis than the decasaccharide fragment. However, in comparison with unfractionated heparin, the 16-18 monosaccharide fragment was only partially effective in preventing thrombosis, despite producing much higher blood levels by anti-Xa assays.It is concluded that the high-affinity binding of a heparin fragment to antithrombin III does not by itself impair venous thrombogenesis, and that the anti-Factor Xa activity of heparin is only a partial expression of its therapeutic potential.

Aspiration Revisited: Prospective Evaluation of a Physiologically Pressurized Model With Animal Correlation and Broader Applicability to Filler Complications

2021 ◽  
Author(s):  
Hyoung-Jin Moon ◽  
Won Lee ◽  
Ji-Soo Kim ◽  
Eun-Jung Yang ◽  
Hema Sundaram
Keyword(s):  
Normal Saline ◽  
False Negative ◽  
Vascular Complications ◽  
Filler Injection ◽  
Negative Results ◽  
Needle Position ◽  
False Negative Results ◽  
In Vivo Testing

Abstract Background Aspiration testing before filler injection is controversial. Some believe that aspiration can help prevent inadvertent intravascular injection, while others cite false-negative results and question its value given that the needle position always changes somewhat during injection procedures. Objectives To test the relation of false-negative results to the viscosity of the material within the needle lumen and determine whether a less viscous material within the needle lumen could decrease the incidence of false-negative results. Methods In vitro aspiration tests were performed using 30-G and 27-G needle gauges, two cross-linked hyaluronic acid fillers, normal saline bags pressurized at 140 and 10 mmHg to mimic human arterial and venous pressures, and three needle lumen conditions (normal saline, air, and filler). Testing was repeated three times under each study condition (72 tests in total). For in vivo correlation, aspiration tests were performed on femoral arteries and central auricular veins in three rabbits (4–5 aspirations per site, 48 tests in total). Results In vitro and in vivo testing using 30-G needles containing filler both showed false-negative results on aspiration testing. In vitro and in vivo testing using needles containing saline or air showed positive findings. Conclusions False-negative results from aspiration testing may be reduced by pre-filling the needle lumen with saline rather than a filler. The pressurized system may help overcome challenges of animal models with intravascular pressures significantly different from those of humans. The adaptability of this system to mimic various vessel pressures may facilitate physiologically relevant studies of vascular complications.

scholarly journals Effective decellularisation of human saphenous veins for biocompatible arterial tissue engineering applications: Bench optimisation and feasibility in vivo testing

2021 ◽  
Vol 12 ◽  
pp. 204173142098752
Author(s):  
Nadiah S Sulaiman ◽  
Andrew R Bond ◽  
Vito D Bruno ◽  
John Joseph ◽  
Jason L Johnson ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Mechanical Strength ◽  
Vascular Tissue ◽  
Sodium Dodecyl ◽  
Host Cells ◽  
Replacement Model ◽  
In Vivo Testing ◽  
Vascular Scaffolds

Human saphenous vein (hSV) and synthetic grafts are commonly used conduits in vascular grafting, despite high failure rates. Decellularising hSVs (D-hSVs) to produce vascular scaffolds might be an effective alternative. We assessed the effectiveness of a detergent-based method using 0% to 1% sodium dodecyl sulphate (SDS) to decellularise hSV. Decellularisation effectiveness was measured in vitro by nuclear counting, DNA content, residual cell viability, extracellular matrix integrity and mechanical strength. Cytotoxicity was assessed on human and porcine cells. The most effective SDS concentration was used to prepare D-hSV grafts that underwent preliminary in vivo testing using a porcine carotid artery replacement model. Effective decellularisation was achieved with 0.01% SDS, and D-hSVs were biocompatible after seeding. In vivo xeno-transplantation confirmed excellent mechanical strength and biocompatibility with recruitment of host cells without mechanical failure, and a 50% patency rate at 4-weeks. We have developed a simple biocompatible methodology to effectively decellularise hSVs. This could enhance vascular tissue engineering toward future clinical applications.

scholarly journals DDEL-12. NANOPARTICLE DELIVERY OF DOXORUBICIN FOR THE TREATMENT OF DIFFUSE INTRINSIC PONTINE GLIOMA (DIPG)

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii286-iii286
Author(s):  
Caitlin Ung ◽  
Maria Tsoli ◽  
Jie Liu ◽  
Domenico Cassano ◽  
Dannielle Upton ◽  
...  
Keyword(s):  
Treatment Strategies ◽  
Pediatric Brain Tumors ◽  
Diffuse Intrinsic Pontine Glioma ◽  
Confocal Imaging ◽  
Cell Content ◽  
Potent Effect ◽  
Orthotopic Mouse Model ◽  
In Vivo Testing

Abstract DIPGs are the most aggressive pediatric brain tumors. Currently, the only treatment is irradiation but due to its palliative nature patients die within 12 months. Effective delivery of chemotherapy across the blood-brain barrier (BBB) has been a key challenge for the eradication of this disease. We have developed a novel gold nanoparticle functionalised with human serum albumin (Au-NP, 98.8 ±19 nm) for the delivery of doxorubicin. In this study, we evaluated the cytotoxic efficacy of doxorubicin delivered through gold nanoparticles (Au-NP-Dox). We found that DIPG neurospheres were equally sensitive to doxorubicin and Au-NP-Dox (at equimolar concentration) by alamar blue assay. Colony formation assays demonstrated a significantly more potent effect of Au-NP-Dox compared to doxorubicin alone, while the Au-NP had no effect. Furthermore, western blot analysis indicated increased apoptotic markers cleaved Parp, caspase 3/7 and phosphorylated H2AX in Au-NP-Dox treated DIPG neurospheres. Live cell content and confocal imaging demonstrated significantly higher uptake of Au-NP-Dox compared to doxorubicin alone. Treatment of a DIPG orthotopic mouse model with Au-NP-Dox showed no signs of toxicity with stable weights being maintained during treatment. However, in contrast to the above in vitro findings the in vivo study showed no anti-tumor effect possibly due to poor penetration of Au-NP-Dox into the brain. We are currently evaluating whether efficacy can be improved using measures to open the BBB transiently. This study highlights the need for rigorous in vivo testing of new treatment strategies before clinical translation to reduce the risk of administration of ineffective treatments.

In vitro and in vivo testing and correlation for oral controlled/ modified release dosage forms. report of the 2nd workshop held December 1988, Washington, DC. U.S.A.

1990 ◽  
Vol 14 (1) ◽  
pp. 95-106 ◽  
Author(s):  
Jerome P. Skelly ◽  
Gordon L. Amidon ◽  
William H. Barr ◽  
Leslie Z. Benet ◽  
James E. Carter ◽  
...  
Keyword(s):  
Dosage Forms ◽  
Washington Dc ◽  
Modified Release ◽  
In Vivo Testing

scholarly journals The Topical Nanodelivery of Vismodegib Enhances Its Skin Penetration and Performance In Vitro While Reducing Its Toxicity In Vivo

Pharmaceutics ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 186
Author(s):  
Maria Natalia Calienni ◽  
Daniela Maza Vega ◽  
C. Facundo Temprana ◽  
María Cecilia Izquierdo ◽  
David E. Ybarra ◽  
...  
Keyword(s):  
Side Effects ◽  
Water Solubility ◽  
Polymeric Micelles ◽  
Skin Penetration ◽  
Distribution Volume ◽  
And Performance ◽  
Oral Doses ◽  
Advanced Basal Cell Carcinoma

Vismodegib is a first-in-class inhibitor for advanced basal cell carcinoma treatment. Its daily oral doses present a high distribution volume and several side effects. We evaluated its skin penetration loaded in diverse nanosystems as potential strategies to reduce side effects and drug quantities. Ultradeformable liposomes, ethosomes, colloidal liquid crystals, and dendrimers were able to transport Vismodegib to deep skin layers, while polymeric micelles failed at this. As lipidic systems were the most effective, we assessed the in vitro and in vivo toxicity of Vismodegib-loaded ultradeformable liposomes, apoptosis, and cellular uptake. Vismodegib emerges as a versatile drug that can be loaded in several delivery systems for topical application. These findings may be also useful for the consideration of topical delivery of other drugs with a low water solubility.

scholarly journals Expression and Characterization of the Flocculin Flo11/Muc1, a Saccharomyces cerevisiae Mannoprotein with Homotypic Properties of Adhesion

2007 ◽  
Vol 6 (12) ◽  
pp. 2214-2221 ◽  
Author(s):  
Lois M. Douglas ◽  
Li Li ◽  
Yang Yang ◽  
A. M. Dranginis
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Biofilm Formation ◽  
In Vitro System ◽  
Glycosylphosphatidylinositol Anchor ◽  
Fungal Adhesion ◽  
Very High ◽  
Molecular Weight Form

ABSTRACT The Flo11/Muc1 flocculin has diverse phenotypic effects. Saccharomyces cerevisiae cells of strain background Σ1278b require Flo11p to form pseudohyphae, invade agar, adhere to plastic, and develop biofilms, but they do not flocculate. We show that S. cerevisiae var. diastaticus strains, on the other hand, exhibit Flo11-dependent flocculation and biofilm formation but do not invade agar or form pseudohyphae. In order to study the nature of the Flo11p proteins produced by these two types of strains, we examined secreted Flo11p, encoded by a plasmid-borne gene, in which the glycosylphosphatidylinositol anchor sequences had been replaced by a histidine tag. A protein of approximately 196 kDa was secreted from both strains, which upon purification and concentration, aggregated into a form with a very high molecular mass. When secreted Flo11p was covalently attached to microscopic beads, it conferred the ability to specifically bind to S. cerevisiae var. diastaticus cells, which flocculate, but not to Σ1278b cells, which do not flocculate. This was true for the 196-kDa form as well as the high-molecular-weight form of Flo11p, regardless of the strain source. The coated beads bound to S. cerevisiae var. diastaticus cells expressing FLO11 and failed to bind to cells with a deletion of FLO11, demonstrating a homotypic adhesive mechanism. Flo11p was shown to be a mannoprotein. Bead-to-cell adhesion was inhibited by mannose, which also inhibits Flo11-dependent flocculation in vivo, further suggesting that this in vitro system is a useful model for the study of fungal adhesion.

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