scholarly journals The Impact of Physicochemical Characteristics on Therapeutic Efficacy of Anticancer Nanomaterials: A Review

2019 ◽  
Vol 11 (02) ◽  
Author(s):  
Bo Wang ◽  
Mensura Sied Filli ◽  
Ahmed Abdalla Ibrahim ◽  
Md Aquib ◽  
Abdul Baset Abbas ◽  
...  
Keyword(s):  
Physicochemical Properties ◽  
Cancer Treatment ◽  
Anticancer Drug ◽  
Therapeutic Efficacy ◽  
Drug Carriers ◽  
Physicochemical Characteristics ◽  
The Body ◽  
Critical Parameters ◽  
The Impact

Cancer is a leading cause of death throughout the world which suffers from treatment failures mainly due to intensive toxicity and lack of effectiveness of conventional drugs. The application of nanotechnology in cancer treatment promises to overcome the drawbacks of conventional drugs/dosage forms and improve their therapeutic efficacy. Nanomaterials have novel properties that influence their in vivo performance. The biological behaviour of nanotechnology-based medicines in the body, which is different from the in vivo performance of conventional drug delivery systems, may provide benefits in pharmaceutical and/or clinical applications including, enhancements in solubility, stability, therapeutic efficacy, minimized side effects, and treatment of diseases. This paper discusses the unique characteristics and distinguished advantages of nanomaterials as anticancer drug carriers. Physicochemical properties of nanomaterials are critical parameters to their clinical translation. Hence, the impact of the main physicochemical properties on the efficacy of anticancer nanomaterials, which are found to effective for cancer treatment and/or diagnosis, are presented. It is important to have reliable and robust characterization techniques that could enable relate physicochemical properties of nanomaterials with their in vivo behaviour. Brief explanation of the different techniques that can be used for studying the various physicochemical characteristics of nanomaterials is given. An important consideration, to achieve fast and successful development of nanotechnology-based anticancer drug products, is assessment and optimization of physicochemical and biopharmaceutical properties at the early stage. Obviously this requires collaboration among the different discovery and development scientists.

scholarly journals A pH-Responsive Multifunctional Nanocarrier in the Application of Chemo-Photodynamic Therapy

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Xiaohong Hu ◽  
Ziyu Gao ◽  
Huaping Tan ◽  
Long Zhang
Keyword(s):  
Anticancer Drug ◽  
Ph Value ◽  
Water Solution ◽  
Drug Carriers ◽  
The Body ◽  
Ph Responsive ◽  
In Vivo Evaluation ◽  
Coarse Surface

In cancer therapy, combined utilization of anticancer drug and photosensitizer attracts increasing interest due to enhanced curative effects and reduced side effects. Since the drug delivery system is an effective method to enhance curative effects, drug carriers for codelivery of the two abovementioned molecules are essentially important for chemophotodynamic therapy. Based on the foundation, a nanocarrier with pH-responsive and targeted properties was designed, prepared, and researched in the work. A pH-sensitive nanoparticle was fabricated by acetylated β-cyclodextrin (Ac-β-CD) using oil-in-water (O/W) emulsion technique. During the fabrication processing, a functional emulgator (gelation-folic acid ester (G-FA)) with a biorecognition domain was absorbed onto the surface of the nanoparticle, which endowed a nanoparticle-targeted property. The nanoparticle exhibited a coarse surface, pH-responsive property, and similar fluorescence characteristic as G-FA. The cell endocytosis profile revealed that equilibrium endocytosis could be reached after being cocultured with 1.0 mg/mL nanoparticle for 8 h. Furthermore, camptothecin (CPT) as an anticancer drug and phthalocyanine (PcZn) as a photosensitizer were encapsulated into the nanoparticle during the fabrication processing. The nanoparticle enhanced the fluorescence effects of PcZn on water solution, and CPT encapsulation proportion was slightly influenced by initial CPT concentration. The pH value influenced the PcZn fluorescence behavior and CPT release behavior of the nanoparticle. In vitro cytoviability evaluation confirmed the therapeutic effect of the nanocarrier on HEP2 cells. Finally, the results of preliminary in vivo evaluation revealed that the reported nanocarrier in the research could inhibit cancer development with little effects on the body weight of mice.

Nanostructured Ketorolac-Tromethamine/MCF: Synthesis, Characterization and Application in Drug Release System

2018 ◽  
Vol 14 (5) ◽  
pp. 432-439 ◽  
Author(s):  
Juliana M. Juarez ◽  
Jorgelina Cussa ◽  
Marcos B. Gomez Costa ◽  
Oscar A. Anunziata
Keyword(s):  
Drug Delivery ◽  
Drug Release ◽  
Therapeutic Efficacy ◽  
Drug Delivery Systems ◽  
Controlled Drug Release ◽  
Delivery Systems ◽  
The Body ◽  
Fickian Diffusion ◽  
Ketorolac Tromethamine

Background: Controlled drug delivery systems can maintain the concentration of drugs in the exact sites of the body within the optimum range and below the toxicity threshold, improving therapeutic efficacy and reducing toxicity. Mesostructured Cellular Foam (MCF) material is a new promising host for drug delivery systems due to high biocompatibility, in vivo biodegradability and low toxicity. Methods: Ketorolac-Tromethamine/MCF composite was synthesized. The material synthesis and loading of ketorolac-tromethamine into MCF pores were successful as shown by XRD, FTIR, TGA, TEM and textural analyses. Results: We obtained promising results for controlled drug release using the novel MCF material. The application of these materials in KETO release is innovative, achieving an initial high release rate and then maintaining a constant rate at high times. This allows keeping drug concentration within the range of therapeutic efficacy, being highly applicable for the treatment of diseases that need a rapid response. The release of KETO/MCF was compared with other containers of KETO (KETO/SBA-15) and commercial tablets. Conclusion: The best model to fit experimental data was Ritger-Peppas equation. Other models used in this work could not properly explain the controlled drug release of this material. The predominant release of KETO from MCF was non-Fickian diffusion.

ANTIMICROBIAL AND POWDER CHARACTERIZATION OF HERBAL DENTIFRICES

INDIAN DRUGS ◽  
2013 ◽  
Vol 50 (11) ◽  
pp. 39-47
Author(s):  
V. K Sharma ◽  
◽  
B. Mazumder ◽  
P. P. Sharma
Keyword(s):  
Oral Cavity ◽  
Physicochemical Properties ◽  
Antimicrobial Effect ◽  
Physicochemical Characteristics ◽  
Water Soluble ◽  
Particle Rearrangement ◽  
Bulk Volume ◽  
The Impact ◽  
Tapped Density

The consumption of edible products strongly recommends the regular hygiene of oral cavity. Various dental products of allopathic and herbal origin are used as dentifrices. The dentifrices are considered safe and effective in terms of cleansing effect of oral cavity and antimicrobial effect against microbes causing bad smell and diseases such as gingivitis, pyorrhea etc. These characteristics of preparations are basically related to physicochemical properties of ingredients present in their composition and some how on directions of their use. In the present study, the marketed allopathic dentifrices coded as Brand I and II and herbal tooth powders coded as Brand III and IV were selected to analyze the impact of physicochemical properties of incorporated ingredients on their cleansing efficiency. The physicochemical characteristics studied were pH, bulk volume, tapped volume, tapped density, bulk density, true density, porosity, flowability, compressibility, compactability, cohesiveness, dispersability, Carr’s index, Hausner’s ratio, water soluble content, alcohol soluble content, foaming index, particle rearrangement behaviour and particle rearrangement constant. The antimicrobial effect of these powders was studied against Staphylococcus sorbinus, Staphylococcus salivarius and Lactobacillus acidophilus. It was observed that some of the physicochemical properties of all powders were different from each other. Marked antimicrobial effect of tooth powders was observed against pathogens. In all preparations, remarkable foaming index was analyzed that was generally considered responsible for cleansing effect.

scholarly journals Alcohol Pattern Consumption Differently Affects the Efficiency of Macrophage Reverse Cholesterol Transport in Vivo

Nutrients ◽  
2018 ◽  
Vol 10 (12) ◽  
pp. 1885
Author(s):  
Daniela Greco ◽  
Simone Battista ◽  
Laura Mele ◽  
Antonio Piemontese ◽  
Bianca Papotti ◽  
...  
Keyword(s):  
Reverse Cholesterol Transport ◽  
Disease Risk ◽  
Cardiovascular Disease Risk ◽  
The Body ◽  
Cholesterol Transport ◽  
Drinking Patterns ◽  
Cardiovascular Morbidity And Mortality ◽  
Short Period ◽  
The Impact

It has been well established that moderate alcohol consumption inversely correlates with cardiovascular morbidity and mortality, whereas binge alcohol drinking increases cardiovascular disease risk. The aim of this study was to assess in vivo the impact of different drinking patterns on reverse cholesterol transport (RCT); the atheroprotective process leading to the removal of excess cholesterol from the body. RCT was measured with a standardized, radioisotope-based technique in three groups of atherosclerosis-prone apolipoprotein E knock out mice: Placebo group, receiving water, which would mimic the abstainers; moderate group, receiving 0.8 g/kg alcohol/day for 28 days, which would mimic a moderate intake; binge group, receiving 0.8 g/kg alcohol/day for 5 days/week, followed by the administration of 2.8 g/kg alcohol/day for 2 days/week, which would mimic a heavy intake in a short period. Mice in the binge drinking group displayed an increase in total cholesterol, high density lipoprotein cholesterol (HDL-c) and non-HDL-c (all p < 0.0001 vs. placebo), and a significantly reduced elimination of fecal cholesterol. The moderate consumption did not lead to any changes in circulating lipids, but slightly improved cholesterol mobilization along the RCT pathway. Overall, our data confirm the importance of considering not only the total amount, but also the different consumption patterns to define the impact of alcohol on cardiovascular risk.

scholarly journals Impact of Mucin on Drug Diffusion: Development of a Straightforward In Vitro Method for the Determination of Drug Diffusivity in the Presence of Mucin

Pharmaceutics ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 168 ◽  
Author(s):  
Margherita Falavigna ◽  
Paul Stein ◽  
Gøril Flaten ◽  
Massimiliano di Cagno
Keyword(s):  
Drug Interaction ◽  
Drug Absorption ◽  
Cost Effective ◽  
Physicochemical Characteristics ◽  
In Vivo Studies ◽  
Phospholipid Vesicle ◽  
Mucus Layer ◽  
The Impact

Mucosal drug delivery accounts for various administration routes (i.e., oral, vaginal, ocular, pulmonary, etc.) and offers a vast surface for the permeation of drugs. However, the mucus layer which shields and lubricates all mucosal tissues can compromise drugs from reaching the epithelial site, thus affecting their absorption and therapeutic effect. Therefore, the effect of the mucus layer on drug absorption has to be evaluated early in the drug-development phase, prior to in vivo studies. For this reason, we developed a simple, cost-effective and reproducible method employing UV-visible localized spectroscopy for the assessment of the interaction between mucin and drugs with different physicochemical characteristics. The mucin–drug interaction was investigated by measuring the drug relative diffusivity (Drel) in the presence of mucin, and the method was validated by fitting experimental and mathematical data. In vitro permeability studies were also performed using the mucus-covered artificial permeation barrier (mucus–PVPA, Phospholipid Vesicle-based Permeation Assay) for comparison. The obtained results showed that the diffusion of drugs was hampered by the presence of mucin, especially at higher concentrations. This novel method proved to be suitable for the investigation on the extent of mucin–drug interaction and can be successfully used to assess the impact that the mucus layer has on drug absorption.

Magneto-thermally responsive hydrogels for bladder cancer treatment: Therapeutic efficacy and in vivo biodistribution

2015 ◽  
Vol 136 ◽  
pp. 625-633 ◽  
Author(s):  
Manish K. Jaiswal ◽  
Lina Pradhan ◽  
Shaleen Vasavada ◽  
Mrinmoy De ◽  
H.D. Sarma ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cancer Treatment ◽  
Therapeutic Efficacy ◽  
Thermally Responsive ◽  
In Vivo Biodistribution ◽  
Responsive Hydrogels

scholarly journals Influens of mole rats burrow activity to restore the soils proteolytic activity in terms of their man-made pollution

2016 ◽  
Vol 17 (3-4) ◽  
pp. 107-111
Author(s):  
T. A. Zamesova
Keyword(s):  
Heavy Metals ◽  
Metal Concentration ◽  
Proteolytic Activity ◽  
The Body ◽  
Activity Level ◽  
Forming Process ◽  
Vital Functions ◽  
The Impact ◽  
Burrow Activity

Heavy metals, especially their large concentration, is toxic for all living creatures because they are accumulating in the living things tissues. Theirs excessive levels evoke coagulation of proteins that cause immediate death of cells. Heavy metals get into the ground by different ways: directly because of using, precipitation, industrial pollution. Their impacts may be either time limited and have low toxicity or, alternatively, it may be long-termed and expressing the pollutants' ability to accumulate them in the body and supply chains. In the edaphotop block of land biogeocenosis most of the transformation processes begin with soil degradation ones. This leads to disruption of soil-forming process cycle of matter and biological productivity of systems. Optimization of a particular system or a block is possible only by acting on their biological relations, which is responsible for managing the system. Distortion or optimization of relations occurs with the animals environmental-forming, the component of which is animals burrow activity. As a result of it, water and chemicals are being reallocated in soil depths, thermal and aeration modes are changed, formed typical zoogenous micro relief with specific physical and chemical properties of the soil. This improves the living conditions of soil micro-organisms. Last ones are involved in soil enzyme activity forming. Enzymes involved in important biochemical processes: synthesis and humus decomposition, hydrolysis of organic compounds, the schedule remains of plants and microorganisms and converted them available to fixation, fix loose items, are actively involved in the cycling of essential elements for plants, in oxidation renewable reactions, etc. It is possible to determine the extent of microorganism’s activity by means of indexes of soil proteolytic activity. Conducted studies of the impact for animals burrow activity on the soils proteolytic activity for artificial forest under conditions of heavy metal pollution. Control plots were contaminated by lead with concentrations of 32; 160; 320 mg/kg of soil, which correspond to the maximum permissible concentration of 1; 5; 10 MAC. Samples were taken at 1st, 3rd and 15th months after contamination; proteolytic activity was determined by the Mishustin application method. Current proteolytic activity of soil is determined in vivo. It is the result of microorganism’s vital functions. And in turn can be an indicator of microbial activity. Contamination of lead depressing vital functions for soil microorganisms. This effect is more noticeable in the first month after contamination. The characteristic dependence of the soil proteolytic activity on metal concentration was observed also, the higher the MPC, the lower proteolytic activity level. The characteristics' dependence of soil proteolytic activity on metal concentration were also observed: the higher MPC, the lower the activity level. It was shown that on the mole rats burrows-dug with lead contaminated the medium proteolytic activity level exceeded control 1.9; 1.76 and 1.53 times respectively, at 1st; 3rd and 15th months after contamination. Based on this we can say that burrowing activity of animals inhibits inhibitory effect of heavy metals and plays an important role in the self-cleaning environment.

scholarly journals Hemoglobin stimulates vigorous growth of Streptococcus pneumoniae and shapes the pathogen's global transcriptome

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Fahmina Akhter ◽  
Edroyal Womack ◽  
Jorge E. Vidal ◽  
Yoann Le Breton ◽  
Kevin S. McIver ◽  
...  
Keyword(s):  
Streptococcus Pneumoniae ◽  
Positive Influence ◽  
The Body ◽  
Host Proteins ◽  
Vigorous Growth ◽  
Cultivation In Vitro ◽  
The Impact ◽  
Heme Binding Protein

Abstract Streptococcus pneumoniae (Spn) must acquire iron from the host to establish infection. We examined the impact of hemoglobin, the largest iron reservoir in the body, on pneumococcal physiology. Supplementation with hemoglobin allowed Spn to resume growth in an iron-deplete medium. Pneumococcal growth with hemoglobin was unusually robust, exhibiting a prolonged logarithmic growth, higher biomass, and extended viability in both iron-deplete and standard medium. We observed the hemoglobin-dependent response in multiple serotypes, but not with other host proteins, free iron, or heme. Remarkably, hemoglobin induced a sizable transcriptome remodeling, effecting virulence and metabolism in particular genes facilitating host glycoconjugates use. Accordingly, Spn was more adapted to grow on the human α − 1 acid glycoprotein as a sugar source with hemoglobin. A mutant in the hemoglobin/heme-binding protein Spbhp-37 was impaired for growth on heme and hemoglobin iron. The mutant exhibited reduced growth and iron content when grown in THYB and hemoglobin. In summary, the data show that hemoglobin is highly beneficial for Spn cultivation in vitro and suggest that hemoglobin might drive the pathogen adaptation in vivo. The hemoglobin receptor, Spbhp-37, plays a role in mediating the positive influence of hemoglobin. These novel findings provide intriguing insights into pneumococcal interactions with its obligate human host.

Developments in the Application of 1,2,3-Triazoles in Cancer Treatment

2020 ◽  
Vol 15 (2) ◽  
pp. 92-112 ◽  
Author(s):  
Katerina I. Slavova ◽  
Lozan T. Todorov ◽  
Nataliya P. Belskaya ◽  
Mauricio A. Palafox ◽  
Irena P. Kostova
Keyword(s):  
Drug Discovery ◽  
Cancer Treatment ◽  
Anticancer Activity ◽  
Medical Science ◽  
Modern Society ◽  
Cancer Drug ◽  
Vast Number ◽  
The Impact

Background: The impact of cancer on modern society cannot be emphasized enough in terms of both economic and human costs. Cancer treatments are known, unfortunately, for their side effects – frequently numerous and severe. Drug resistance is another issue medical professionals have to tackle when dealing with neoplastic illnesses. Cancer rates are rising worldwide due to various factors - low-quality nutrition, air and water pollution, tobacco use, etc. For those and many other reasons, drug discovery in the field of oncology is a top priority in modern medical science. Objective: To present the reader with the latest in cancer drug discovery with regard to 1,2,3-triazole- containing molecules in a clear, concise way so as to make the present review a useful tool for researchers. Methods: Available information present on the role of 1,2,3-triazoles in cancer treatment was collected. Data was collected from scientific literature, as well as from patents. Results: A vast number of triazole-containing molecules with antiproliferative properties have been proposed, synthesized and tested for anticancer activity both in vitro and in vivo. The substances vary greatly when considering molecular structure, proposed mechanisms of action and affected cancer cell types. Conclusion: Triazole-containing molecules with anticancer activity are being widely synthesized and extensively tested. They vary significantly in terms of both structure and mechanism of action. The methods for their preparation and administration are well established and with proven reproducibility. These facts suggest that triazoles may play an important role in the discovery of novel antiproliferative medications with improved effectiveness and safety profile.

Quantitative Assessment of the Impact of Ex Vivo Manipulation on the In Vivo Functionality of Human T Cells in RAG2−/− γc−/− mice.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 450-450
Author(s):  
Rozemarijn S. van Rijn ◽  
Elles R. Simonetti ◽  
Gert Storm ◽  
Mark Bonyhadi ◽  
Anton Hagenbeek ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Ex Vivo ◽  
T Cell Subsets ◽  
Critical Parameters ◽  
In Vivo Evaluation ◽  
Human T Cells ◽  
The Impact

Abstract T cells retrovirally modified to express therapeutic genes encoding cytokines, exogenous TCRs or suicide molecules represent a novel class of immune therapeutics of great potency. However, recent clinical trials using retrovirally-modified T cells have indicated that T cells exhibit a diminished reactivity upon ex vivo manipulation. In addition, virus-specific memory T cells seem to be lost during gene transfer. In a BNML rat model we have shown that the culture procedure is one of the critical parameters. To preserve T cell reactivity, reliable models are required which permit readout of human T cell activity. We recently developed a huPBMC-RAG2−/−γc−/− mouse model for xenogeneic graft-versus-host disease (xGVHD), in which iv injection of 15 x 106 human T cells into RAG2−/−γc−/− mice consistently leads to high level engraftment and lethal xGVHD within 3 weeks in 80% of mice (van Rijn et al, Blood 2003). We have now used this model to analyze in vivo functionality of human T cells following different ex vivo culture procedures. For this, we cultured human T cells for 7 days with either of the two currently available clinically applicable stimulation conditions: 1) via CD3 and 2) via CD3/CD28. In addition, we included CD3/CD28/4-1BB stimulation to explore the effect of extensive costimulation. Mice were injected with escalating doses T cells. HuCD45+ cells in peripheral blood were measured by FACS. Lethal xGVHD occurred at only 6 times (90.106) the dose of fresh cells for CD3-stimulated T cells and 3 times for CD3/28- or CD3/28/4-1BB-stimulated cells. About 20% of surviving mice developed chronic xGVHD, independent of culture method. While lethal xGVHD was always associated with very high levels of engraftment (up to 95%) engraftment levels in chronic mice ranged from 1–75%. To compare the impact of the different culture conditions on in vivo T cell function, we analyzed engraftment potential. The fraction of huCD45+ cells was plotted against the time and the areas under the curves were compared. Based on a total of 68 mice, statistical analysis showed a 2-fold improvement of engraftment potential for C28-costimulated human T cells compared to CD3-stimulated cells (P&lt;0.0001). Additional ligation of 4-1BB did not increase engraftment potential. In addition, different T cell subsets (naïve, memory, effector) were monitored based on the combined expression of CD45RA, CD27 and CCR7. For all primary T cells and variably cultured T cells, a strikingly similar pattern was observed in vivo. After 3 weeks mainly effector and memory effector T cells (both CD4+ and CD8+) could be detected, suggesting a (xeno-)antigen-driven survival and expansion. This was a very consistent observation independent of donor, culture condition, engraftment level or severity of disease. In conclusion, in vitro costimulation preserves in vivo functionality of human T cells and should therefore be included in future clinical protocols for ex vivo manipulation of T cells. These data show the feasibility to use the huPBMC-RAG2−/−γc−/− model for in vivo evaluation of in vitro effects on human T cells. This model is the most sensitive to date for in vivo evaluation of human T cells and will be a promising new tool for the study of human T cells in, for instance, autoimmune disease, cancer and infectious diseases like AIDS.

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