scholarly journals In Vitro and In Vivo Response to Low-Modulus PMMA-Based Bone Cement

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Elin Carlsson ◽  
Gemma Mestres ◽  
Kiatnida Treerattrakoon ◽  
Alejandro López ◽  
Marjam Karlsson Ott ◽  
...  
Keyword(s):  
Linoleic Acid ◽  
Immune Cells ◽  
Castor Oil ◽  
In Vitro Cytotoxicity ◽  
Bone Cements ◽  
Human Osteoblast ◽  
Flow Cytometry Analysis ◽  
Low Modulus

The high stiffness of acrylic bone cements has been hypothesized to contribute to the increased number of fractures encountered after vertebroplasty, which has led to the development of low-modulus cements. However, there is no data available on the in vivo biocompatibility of any low-modulus cement. In this study, the in vitro cytotoxicity and in vivo biocompatibility of two types of low-modulus acrylic cements, one modified with castor oil and one with linoleic acid, were evaluated using human osteoblast-like cells and a rodent model, respectively. While the in vitro cytotoxicity appeared somewhat affected by the castor oil and linoleic acid additions, no difference could be found in the in vivo response to these cements in comparison to the base, commercially available cement, in terms of histology and flow cytometry analysis of the presence of immune cells. Furthermore, the in vivo radiopacity of the cements appeared unaltered. While these results are promising, the mechanical behavior of these cements in vivo remains to be investigated.

scholarly journals Direct Comparison of Two Kinds of Linoleic Acid-docetaxel Derivatives: in Vitro Cytotoxicity and in Vivo Antitumor Activity

2021 ◽  
Author(s):  
Lirui Jia ◽  
Ying Liu ◽  
Meng Li ◽  
Yongjun Wang ◽  
Zhonggui He
Keyword(s):  
Linoleic Acid ◽  
Structural Integrity ◽  
In Vitro Cytotoxicity ◽  
Anticancer Efficacy ◽  
Distribution Study ◽  
In Vivo Antitumor Activity ◽  
Target Effect ◽  
Highly Hydrophobic

Abstract Rational designed lipid-drug derivatives provide a favorable approach to improve the druggability of highly hydrophobic prototypes. It has been regarded as common sense that good cytotoxicity is the guarantee of superior anticancer efficacy for candidate derivatives screening. Here, we established two lipid-drug derivatives with different bridge bonds (ester bond and mono thioether bond) linking docetaxel and linoleic acid. The IC50 of DSL NPs (DTX-S-LA nanoparticles) and DL NPs (DTX-LA nanoparticles) were 4.02 and 209.6 ng/mL (DTX equivalent concentration), respectively. However, DL NPs unexpectedly showed stronger tumor inhibition abilities than DSL NPs. To explain the non-positive correlation between cytotoxicity and anticancer efficacy, more experiments were carried out in depth. Remarkably, the drug release studies in blood and PK study both suggested that the DL NPs were more stable to remain the structural integrity in circulation, which resulted in more accumulation in tumor sites. As verified by the bio-distribution study, DL NPs performed a superior target effect than DSL NPs in tumors. Our data indicated that the biological fates of so-called smart bond inserted derivatives in vivo are complicated, thus, simple cytotoxicity is not enough for derivatives screening, and the comprehensive understanding of both in vitro and in vivo behaviors is essential.

Mixed Micelles as Nano Polymer Therapeutics of Docetaxel: Increased In vitro Cytotoxicity and Decreased In vivo Toxicity

2018 ◽  
Vol 15 (4) ◽  
pp. 564-575 ◽  
Author(s):  
Arehalli S. Manjappa ◽  
Popat S. Kumbhar ◽  
Prajakta S. Khopade ◽  
Ajit B. Patil ◽  
John I. Disouza
Keyword(s):  
Mixed Micelles ◽  
In Vitro Cytotoxicity ◽  
Polymer Therapeutics ◽  
In Vivo Toxicity

Mannose Conjugated Starch Nanoparticles for Preferential Targeting of Liver Cancer

2020 ◽  
Vol 17 ◽  
Author(s):  
Akhlesh Kumar Jain ◽  
Hitesh Sahu ◽  
Keerti Mishra ◽  
Suresh Thareja
Keyword(s):  
Side Effects ◽  
Liver Cancer ◽  
Entrapment Efficiency ◽  
Xrd Analysis ◽  
In Vitro Cytotoxicity ◽  
Physical Interaction ◽  
Scanning Calorimetry ◽  
Starch Nanoparticles

Aim: To design D-Mannose conjugated 5-Fluorouracil (5-FU) loaded Jackfruit seed starch nanoparticles (JFSSNPs) for site specific delivery. Background: Liver cancer is the third leading cause of death in world and fifth most often diagnosed cancer is the major global threat to public health. Treatment of liver cancer with conventional method bears several side effects, thus to undertake these side effects as a formulation challenge, it is necessary to develop novel target specific drug delivery system for the effective and better localization of drug into the proximity of target with restricting the movement of drug in normal tissues. Objective: To optimize and characterize the developed D-Mannose conjugated 5-Fluorouracil (5-FU) loaded Jackfruit seed starch nanoparticles (JFSSNPs) for effective treatment of liver cancer. Materials and methods: 5-FU loaded JFSSNPs were prepared and optimized formulation had higher encapsulation efficiency were conjugated with D-Mannose. These formulations were characterized for size, morphology, zeta potential, X-Ray Diffraction, and Differential Scanning Calorimetry. Potential of NPs were studied using in vitro cytotoxicity assay, in vivo kinetic studies and bio-distribution studies. Result and discussion: 5-Fluorouracil loaded NPs had particle size between 336 to 802nm with drug entrapment efficiency was between 64.2 to 82.3%. In XRD analysis, 5-FU peak was diminished in the diffractogram, which could be attributed to the successful incorporation of drug in amorphous form. DSC study suggests there was no physical interaction between 5- FU and Polymer. NPs showed sustained in vitro 5-FU release up to 2 hours. In vivo, mannose conjugated NPs prolonged the plasma level of 5-FU and assist selective accumulation of 5-FU in the liver (vs other organs spleen, kidney, lungs and heart) compared to unconjugated one and plain drug. Conclusion: In vivo, bio-distribution and plasma profile studies resulted in significantly higher concentration of 5- Fluorouracil liver suggesting that these carriers are efficient, viable, and targeted carrier of 5-FU treatment of liver cancer.

scholarly journals Formulation and in vitro evaluation of self-nanoemulsifying liquisolid tablets of furosemide

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Lena Dalal ◽  
Abdul Wahab Allaf ◽  
Hind El-Zein
Keyword(s):  
Theoretical Model ◽  
Castor Oil ◽  
In Vivo Studies ◽  
Coating Materials ◽  
Peg 400 ◽  
The Mean ◽  
Usp Apparatus ◽  
Solid System

AbstractSelf-nanoemulsifying drug delivery systems (SNEDDS) were used to enhance the dissolution rate of furosemide as a model for class IV drugs and the system was solidified into liquisolid tablets. SNEDDS of furosemide contained 10% Castor oil, 60% Cremophor EL, and 30% PEG 400. The mean droplets size was 17.9 ± 4.5 nm. The theoretical model was used to calculate the amounts of the carrier (Avicel PH101) and coating materials (Aerosil 200) to prepare liquisolid powder. Carrier/coating materials ratio of 5/1 was used and Ludipress was added to the solid system, thus tablets with hardness of 45 ± 2 N were obtained. Liquisolid tablets showed 2-folds increase in drug release as compared to the generic tablets after 60 min in HCl 0.1 N using USP apparatus-II. Furosemide loaded SNEDDS tablets have great prospects for further in vivo studies, and the theoretical model is useful for calculating the adequate amounts of adsorbents required to solidify these systems.

scholarly journals FOXE1-Dependent Regulation of Macrophage Chemotaxis by Thyroid Cells In Vitro and In Vivo

2021 ◽  
Vol 22 (14) ◽  
pp. 7666
Author(s):  
Sara C. Credendino ◽  
Marta De Menna ◽  
Irene Cantone ◽  
Carmen Moccia ◽  
Matteo Esposito ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Immune Cells ◽  
Cancer Susceptibility ◽  
Macrophage Infiltration ◽  
M2 Macrophage ◽  
Thyroid Cells ◽  
Transcriptional Alterations ◽  
Cancer Phenotypes

Forkhead box E1 (FOXE1) is a lineage-restricted transcription factor involved in thyroid cancer susceptibility. Cancer-associated polymorphisms map in regulatory regions, thus affecting the extent of gene expression. We have recently shown that genetic reduction of FOXE1 dosage modifies multiple thyroid cancer phenotypes. To identify relevant effectors playing roles in thyroid cancer development, here we analyse FOXE1-induced transcriptional alterations in thyroid cells that do not express endogenous FOXE1. Expression of FOXE1 elicits cell migration, while transcriptome analysis reveals that several immune cells-related categories are highly enriched in differentially expressed genes, including several upregulated chemokines involved in macrophage recruitment. Accordingly, FOXE1-expressing cells induce chemotaxis of co-cultured monocytes. We then asked if FOXE1 was able to regulate macrophage infiltration in thyroid cancers in vivo by using a mouse model of cancer, either wild type or with only one functional FOXE1 allele. Expression of the same set of chemokines directly correlates with FOXE1 dosage, and pro-tumourigenic M2 macrophage infiltration is decreased in tumours with reduced FOXE1. These data establish a novel link between FOXE1 and macrophages recruitment in the thyroid cancer microenvironment, highlighting an unsuspected function of this gene in the crosstalk between neoplastic and immune cells that shape tumour development and progression.

scholarly journals A molecular architectural design that promises potent antimicrobial activity against multidrug-resistant pathogens

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Bing Yuan ◽  
Jiaojiao Liu ◽  
Zhixiong Deng ◽  
Lin Wei ◽  
Wenwen Li ◽  
...  
Keyword(s):  
Architectural Design ◽  
Building Blocks ◽  
Multidrug Resistant ◽  
In Vitro Cytotoxicity ◽  
Antimicrobial Drugs ◽  
Minimal Inhibitory Concentrations ◽  
Antimicrobial Efficiency ◽  
Multidrug Resistant Pathogens

AbstractAddressing the devastating threat of drug-resistant pathogens requires the discovery of new antibiotics with advanced action mechanisms and/or novel strategies for drug design. Herein, from a biophysical perspective, we design a class of synthetic antibacterial complexes with specialized architectures based on melittin (Mel), a natural antimicrobial peptide, and poly(ethylene glycol) (PEG), a clinically available agent, as building blocks that show potent and architecture-modulated antibacterial activity. Among the complexes, the flexibly linear complex consisting of one Mel terminally connected with a long-chained PEG (e.g., PEG12k–1*Mel) shows the most pronounced improvement in performance compared with pristine Mel, with up to 500% improvement in antimicrobial efficiency, excellent in vitro activity against multidrug-resistant pathogens (over a range of minimal inhibitory concentrations of 2–32 µg mL−1), a 68% decrease in in vitro cytotoxicity, and a 57% decrease in in vivo acute toxicity. A lipid-specific mode of action in membrane recognition and an accelerated “channel” effect in perforating the bacterial membrane of the complex are described. Our results introduce a new way to design highly efficient and low-toxicity antimicrobial drugs based on architectural modulations with clinically available agents.

scholarly journals Assessment of SnFe2O4 Nanoparticles for Potential Application in Theranostics: Synthesis, Characterization, In Vitro, and In Vivo Toxicity

Materials ◽  
2021 ◽  
Vol 14 (4) ◽  
pp. 825
Author(s):  
Saman Sargazi ◽  
Mohammad Reza Hajinezhad ◽  
Abbas Rahdar ◽  
Muhammad Nadeem Zafar ◽  
Aneesa Awan ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
A549 Cells ◽  
In Vitro Cytotoxicity ◽  
Hek293 Cells ◽  
Hydrothermal Route ◽  
X Ray ◽  
Tin Chloride ◽  
Bet Analysis

In this research, tin ferrite (SnFe2O4) NPs were synthesized via hydrothermal route using ferric chloride and tin chloride as precursors and were then characterized in terms of morphology and structure using Fourier-transform infrared spectroscopy (FTIR), Ultraviolet–visible spectroscopy (UV-Vis), X-ray power diffraction (XRD), Scanning electron microscopy (SEM), Transmission electron microscopy (TEM), and Brunauer–Emmett–Teller (BET) method. The obtained UV-Vis spectra was used to measure band gap energy of as-prepared SnFe2O4 NPs. XRD confirmed the spinel structure of NPs, while SEM and TEM analyses disclosed the size of NPs in the range of 15–50 nm and revealed the spherical shape of NPs. Moreover, energy dispersive X-ray spectroscopy (EDS) and BET analysis was carried out to estimate elemental composition and specific surface area, respectively. In vitro cytotoxicity of the synthesized NPs were studied on normal (HUVEC, HEK293) and cancerous (A549) human cell lines. HUVEC cells were resistant to SnFe2O4 NPs; while a significant decrease in the viability of HEK293 cells was observed when treated with higher concentrations of SnFe2O4 NPs. Furthermore, SnFe2O4 NPs induced dramatic cytotoxicity against A549 cells. For in vivo study, rats received SnFe2O4 NPs at dosages of 0, 0.1, 1, and 10 mg/kg. The 10 mg/kg dose increased serum blood urea nitrogen and creatinine compared to the controls (P < 0.05). The pathology showed necrosis in the liver, heart, and lungs, and the greatest damages were related to the kidneys. Overall, the in vivo and in vitro experiments showed that SnFe2O4 NPs at high doses had toxic effects on lung, liver and kidney cells without inducing toxicity to HUVECs. Further studies are warranted to fully elucidate the side effects of SnFe2O4 NPs for their application in theranostics.

scholarly journals Resolvin D1 reduces cancer growth stimulating a protective neutrophil-dependent recruitment of anti-tumor monocytes

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Domenico Mattoscio ◽  
Elisa Isopi ◽  
Alessia Lamolinara ◽  
Sara Patruno ◽  
Alessandro Medda ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Growth Curve ◽  
Immune Cells ◽  
Cancer Growth ◽  
Resolvin D1 ◽  
Anti Cancer ◽  
Classical Monocytes ◽  
Human And Mouse

Abstract Background Innovative therapies to target tumor-associated neutrophils (PMN) are of clinical interest, since these cells are centrally involved in cancer inflammation and tumor progression. Resolvin D1 (RvD1) is a lipid autacoid that promotes resolution of inflammation by regulating the activity of distinct immune and non-immune cells. Here, using human papilloma virus (HPV) tumorigenesis as a model, we investigated whether RvD1 modulates PMN to reduce tumor progression. Methods Growth-curve assays with multiple cell lines and in vivo grafting of two distinct HPV-positive cells in syngeneic mice were used to determine if RvD1 reduced cancer growth. To investigate if and how RvD1 modulates PMN activities, RNA sequencing and multiplex cytokine ELISA of human PMN in co-culture with HPV-positive cells, coupled with pharmacological depletion of PMN in vivo, were performed. The mouse intratumoral immune cell composition was evaluated through FACS analysis. Growth-curve assays and in vivo pharmacological depletion were used to evaluate anti-tumor activities of human and mouse monocytes, respectively. Bioinformatic analysis of The Cancer Genome Atlas (TCGA) database was exploited to validate experimental findings in patients. Results RvD1 decreased in vitro and in vivo proliferation of human and mouse HPV-positive cancer cells through stimulation of PMN anti-tumor activities. In addition, RvD1 stimulated a PMN-dependent recruitment of classical monocytes as key determinant to reduce tumor growth in vivo. In human in vitro systems, exposure of PMN to RvD1 increased the production of the monocyte chemoattractant protein-1 (MCP-1), and enhanced transmigration of classical monocytes, with potent anti-tumor actions, toward HPV-positive cancer cells. Consistently, mining of immune cells infiltration levels in cervical cancer patients from the TCGA database evidenced an enhanced immune reaction and better clinical outcomes in patients with higher intratumoral monocytes as compared to patients with higher PMN infiltration. Conclusions RvD1 reduces cancer growth by activating PMN anti-cancer activities and encouraging a protective PMN-dependent recruitment of anti-tumor monocytes. These findings demonstrate efficacy of RvD1 as an innovative therapeutic able to stimulate PMN reprogramming to an anti-cancer phenotype that restrains tumor growth.

scholarly journals Peptide drugs for photopharmacology: how much of a safety advantage can be gained by photocontrol?

2020 ◽  
Vol 2 (1) ◽  
pp. FDD28 ◽  
Author(s):  
Oleg Babii ◽  
Sergii Afonin ◽  
Tim Schober ◽  
Liudmyla V Garmanchuk ◽  
Liudmyla I Ostapchenko ◽  
...  
Keyword(s):  
Chemotherapeutic Agent ◽  
In Vitro Cytotoxicity ◽  
Pharmacokinetic Parameters ◽  
Cancer Model ◽  
Pharmacokinetic Properties ◽  
Insight Into ◽  
Safety Advantage ◽  
Murine Cancer Model

Aim: To verify whether photocontrol of biological activity could augment safety of a chemotherapeutic agent. Materials & methods: LD50 values for gramicidin S and photoisomeric forms of its photoswitchable diarylethene-containing analogs were determined using mice. The results were compared with data obtained from cell viability measurements taken for the same compounds. Absorption, Distribution, Metabolism, and Elimination (ADME) tests using a murine cancer model were conducted to get insight into the underlying reasons for the observed in vivo toxicity. Results: While in vitro cytotoxicity values of the photoisomers differed substantially, the differences in the observed LD50 values were less pronounced due to unfavorable pharmacokinetic parameters. Conclusion: Despite unfavorable pharmacokinetic properties as in the representative case studied here, there is an overall advantage to be gained in the safety profile of a chemotherapeutic agent via photocontrol. Nevertheless, optimization of the pharmacokinetic parameters of photoisomers is an important issue to be addressed during the development of photopharmacological drugs.

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