scholarly journals Hybrid delivery systems for methotrexate-lipidic liquid crystalline cubic phases and cubosomes with magnetic nanoparticles

2019 ◽  
Author(s):  
Monika Mierzwa ◽  
Pawel Krysinski ◽  
Renata Bilewicz
Keyword(s):  
Magnetic Nanoparticles ◽  
Liquid Crystalline ◽  
Low Frequency ◽  
In Vitro Cytotoxicity ◽  
Cubic Phase ◽  
Hybrid Delivery ◽  
Cubic Phases ◽  
Release Profiles

The release profiles of methotrexate, an anticancer drug, from the monoolein liquid crystalline cubic phases were studied. The cubic phases were used either in the form of a lipidic film deposited onto a glassy carbon electrode surface or in the dispersed form of magnetocubosomes, which are considered a prospective hybrid drug delivery system. Commonly, cubosomes or liposomes are employed, but not in the case of toxic methotrexate, known to block receptors responsible for folate transport into the cells. The release profiles of the drug from the lipidic films were monitored electrochemically and described using the Higuchi model. They were also modified via changes in temperature; the release was faster, although deviating from the model when the temperature was increased. Magnetocubosomes - cubic phase nanoparticles containing hydrophobic magnetic nanoparticles placed in an alternating magnetic field of low frequency and amplitude, stimulated drug release from the suspension, which was monitored spectroscopically. These new biocompatible hybrid materials are very promising, allowing to control the release of the drug at the appropriate sites, but do require further investigations into their in vitro cytotoxicity and in vivo biodistribution.

scholarly journals Lipidic Liquid Crystalline Cubic Phases and Magnetocubosomes as Methotrexate Carriers

Nanomaterials ◽  
2019 ◽  
Vol 9 (4) ◽  
pp. 636 ◽  
Author(s):  
Monika Mierzwa ◽  
Adrianna Cytryniak ◽  
Paweł Krysiński ◽  
Renata Bilewicz
Keyword(s):  
Magnetic Field ◽  
Liquid Crystalline ◽  
Low Frequency ◽  
In Vitro Cytotoxicity ◽  
Cubic Phase ◽  
Folate Transport ◽  
Cubic Phases ◽  
Release Profiles

The release profiles of methotrexate, an anticancer drug, from the monoolein liquid crystalline cubic phases were studied. The cubic phases were used either in the form of a lipidic film deposited onto a glassy carbon electrode surface or in the dispersed form of magnetocubosomes, which are considered a prospective hybrid drug delivery system. Commonly, cubosomes or liposomes are employed, but not in the case of toxic methotrexate, known to block the receptors responsible for folate transport into the cells. The release profiles of the drug from the lipidic films were monitored electrochemically and described using the Higuchi model. They were also modified via changes in temperature; the release was faster, although it deviated from the model when the temperature was increased. Cubic phase nanoparticles (magnetocubosomes) containing hydrophobic magnetic nanoparticles placed in an alternating magnetic field of low frequency and amplitude, stimulated drug release from the suspension, which was monitored spectroscopically. These new biocompatible hybrid nanomaterials in the dispersed form allow to control the release of the drug at the appropriate sites, can be easily separated or relocated under external magnetic field and await further investigations of their in vitro cytotoxicity and in vivo biodistribution.

Chemotherapeutic potential of L-carnosine from stimuli-responsive magnetic nanoparticles against breast cancer model

Nanomedicine ◽  
2020 ◽  
Vol 15 (9) ◽  
pp. 891-911
Author(s):  
Ragwa M Farid ◽  
Passent M E Gaafar ◽  
Heba A Hazzah ◽  
Maged W Helmy ◽  
Ossama Y Abdallah
Keyword(s):  
Magnetic Nanoparticles ◽  
Targeted Delivery ◽  
Physicochemical Characterization ◽  
Tumor Model ◽  
Entrapment Efficiency ◽  
In Vitro Cytotoxicity ◽  
Scanning Calorimetry ◽  
Chemotherapeutic Activity

Aim: L-carnosine-coated magnetic nanoparticles (CCMNPs) were developed to enhance chemotherapeutic activity of carnosine-dipeptide. Materials & methods: Surface grafting of MNPs with carnosine was contended by differential scanning calorimetry, infrared spectroscopy and x-ray diffraction. Physicochemical characterization and in vitro cytotoxicity on MCF-7 cell line was carried out. In vivo chemotherapeutic activity and toxicity was assessed by an Ehrlich Ascites tumor model. Results: CCMNPs possessed monodispersed size (120 nm), ζ (-27.3 mV), magnetization (51.52 emu/g) and entrapment efficiency (88.3%) with sustained release rate. CCMNPs showed 2.3-folds lower IC50 values compared with carnosine solution after 48 h. Targeted CCMNPs were specifically accumulated in tumor showing significant reduction in tumor size with no systemic toxicity. Significant reduction in VEGF and cyclin D1 levels were observed. Conclusion: The developed system endowed with responsiveness to an external stimulus can represent a promising magnetically targeted delivery system for carnosine site specific delivery.

scholarly journals Cationic liposome–nucleic acid nanoparticle assemblies with applications in gene delivery and gene silencing

2016 ◽  
Vol 374 (2072) ◽  
pp. 20150129 ◽  
Author(s):  
Ramsey N. Majzoub ◽  
Kai K. Ewert ◽  
Cyrus R. Safinya
Keyword(s):  
Nucleic Acid ◽  
Gene Delivery ◽  
Gene Silencing ◽  
Liquid Crystalline ◽  
Cationic Liposome ◽  
Endosomal Escape ◽  
Cubic Phase ◽  
Nucleic Acid Therapeutics

Cationic liposomes (CLs) are synthetic carriers of nucleic acids in gene delivery and gene silencing therapeutics. The introduction will describe the structures of distinct liquid crystalline phases of CL–nucleic acid complexes, which were revealed in earlier synchrotron small-angle X-ray scattering experiments. When mixed with plasmid DNA, CLs containing lipids with distinct shapes spontaneously undergo topological transitions into self-assembled lamellar, inverse hexagonal, and hexagonal CL–DNA phases. CLs containing cubic phase lipids are observed to readily mix with short interfering RNA (siRNA) molecules creating double gyroid CL–siRNA phases for gene silencing. Custom synthesis of multivalent lipids and a range of novel polyethylene glycol (PEG)-lipids with attached targeting ligands and hydrolysable moieties have led to functionalized equilibrium nanoparticles (NPs) optimized for cell targeting, uptake or endosomal escape. Very recent experiments are described with surface-functionalized PEGylated CL–DNA NPs, including fluorescence microscopy colocalization with members of the Rab family of GTPases, which directly reveal interactions with cell membranes and NP pathways. In vitro optimization of CL–DNA and CL–siRNA NPs with relevant primary cancer cells is expected to impact nucleic acid therapeutics in vivo . This article is part of the themed issue ‘Soft interfacial materials: from fundamentals to formulation’.

Use of light microscopy in the qualitative and quantitative study of liquid crystalline order

1992 ◽  
Vol 50 (1) ◽  
pp. 264-265
Author(s):  
Christopher Viney
Keyword(s):  
Light Microscopy ◽  
Liquid Crystalline ◽  
Structural Characteristics ◽  
Molecular Order ◽  
Liquid Crystalline Phases ◽  
Convenient Technique ◽  
Liquid Crystalline Materials ◽  
Transparent Windows

Light microscopy is a convenient technique for characterizing molecular order in fluid liquid crystalline materials. Microstructures can usually be observed under the actual conditions that promote the formation of liquid crystalline phases, whether or not a solvent is required, and at temperatures that can range from the boiling point of nitrogen to 600°C. It is relatively easy to produce specimens that are sufficiently thin and flat, simply by confining a droplet between glass cover slides. Specimens do not need to be conducting, and they do not have to be maintained in a vacuum. Drybox or other controlled environmental conditions can be maintained in a sealed chamber equipped with transparent windows; some heating/ freezing stages can be used for this purpose. It is relatively easy to construct a modified stage so that the generation and relaxation of global molecular order can be observed while specimens are being sheared, simulating flow conditions that exist during processing. Also, light only rarely affects the chemical composition or molecular weight distribution of the sample. Because little or no processing is required after collecting the sample, one can be confident that biologically derived materials will reveal many of their in vivo structural characteristics, even though microscopy is performed in vitro.

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 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 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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