scholarly journals Investigation of Cytotoxicity and Cell Uptake of Cationic Beta-Cyclodextrins as Valid Tools in Nasal Delivery

2020 ◽  
Author(s):  
Giovanna Rassu ◽  
Silvia Fancello ◽  
Marta Roldo ◽  
Milo Malanga ◽  
Lajos Szente ◽  
...  
Keyword(s):  
Quaternary Ammonium ◽  
Pharmaceutical Formulations ◽  
Controlled Drug Release ◽  
Cell Uptake ◽  
Nasal Delivery ◽  
Protective Effects ◽  
Suitable Material ◽  
Beta Cyclodextrin ◽  
Cyclodextrin Polymers ◽  
Uptake Studies

Cyclodextrin polymers have high applicability in pharmaceutical formulations due to better biocompatibility, solubility enhancement, loading capacity and controlled drug release than parent the cyclodextrins. The cytotoxicity and cell uptake of new cationic beta-cyclodextrin monomers and polymers were evaluated as suitable material for nasal formulations and their protective effects on cells exposed to hydrogen peroxide were studied. PC12 and CACO-2 cells were selected as the neuronal and epithelial type cells, respectively, to mimic the structure of respiratory and olfactory epithelia of the nasal cavity. All cationic beta-cyclodextrin polymers tested showed dose- and time-dependent toxicity; nevertheless, at 5 µM concentration and 60 min of exposure, the quaternary-ammonium-beta-cyclodextrin soluble polymer could be recognized as non-toxic. Based on these results, fluorescently labelled quaternary-ammonium-beta-cyclodextrin monomer and polymer were selected for uptake studies in CACO-2 cells. The monomeric and polymeric beta-cyclodextrins were internalized in the cytoplasm of CACO-2 cells; the cationic monomer showed higher permeability than the hydroxypropyl-beta-cyclodextrin, employed as comparison. Therefore, these cationic beta-cyclodextrins showed potential as excipients able to improve the nasal absorption of drugs. Furthermore, amino-beta-cyclodextrin and beta-cyclodextrin soluble polymers were able to reduce oxidative damage in PC12 and CACO-2 cells and thus could be studied as bioactive carriers or potential drugs for cells protection against oxidative stress.

scholarly journals Investigation of Cytotoxicity and Cell Uptake of Cationic Beta-Cyclodextrins as Valid Tools in Nasal Delivery

Pharmaceutics ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 658 ◽  
Author(s):  
Giovanna Rassu ◽  
Silvia Fancello ◽  
Marta Roldo ◽  
Milo Malanga ◽  
Lajos Szente ◽  
...  
Keyword(s):  
Quaternary Ammonium ◽  
Pharmaceutical Formulations ◽  
Controlled Drug Release ◽  
Cell Uptake ◽  
Nasal Delivery ◽  
Protective Effects ◽  
Cell Protection ◽  
Beta Cyclodextrin ◽  
Cyclodextrin Polymers ◽  
Uptake Studies

Cyclodextrin polymers have high applicability in pharmaceutical formulations due to better biocompatibility, solubility enhancement, loading capacity and controlled drug release than their parent, cyclodextrins. The cytotoxicity and cell uptake of new cationic beta-cyclodextrin monomers and polymers were evaluated as suitable materials for nasal formulations and their protective effects on cells exposed to hydrogen peroxide were studied. PC12 and CACO-2 cells were selected as the neuronal- and epithelial-type cells, respectively, to mimic the structure of respiratory and olfactory epithelia of the nasal cavity. All cationic beta-cyclodextrin polymers tested showed dose- and time-dependent toxicity; nevertheless, at 5 µM concentration and 60 min of exposure, the quaternary-ammonium-beta-cyclodextrin soluble polymer could be recognized as nontoxic. Based on these results, a fluorescently labelled quaternary-ammonium-beta-cyclodextrin monomer and polymer were selected for uptake studies in CACO-2 cells. The monomeric and polymeric beta-cyclodextrins were internalized in the cytoplasm of CACO-2 cells; the cationic monomer showed higher permeability than the hydroxypropyl-beta-cyclodextrin, employed as comparison. Therefore, these cationic beta-cyclodextrins showed potential as excipients able to improve the nasal absorption of drugs. Furthermore, amino-beta-cyclodextrin and beta-cyclodextrin soluble polymers were able to reduce oxidative damage in PC12 and CACO-2 cells and thus could be studied as bioactive carriers or potential drugs for cell protection against oxidative stress.

scholarly journals Synthesis and tumour cell uptake studies of gadolinium(III)–phosphonium complexes

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Andrew J. Hall ◽  
Amy G. Robertson ◽  
Leila R. Hill ◽  
Louis M. Rendina
Keyword(s):  
Glioblastoma Multiforme ◽  
Tumour Cell ◽  
In Vitro Cytotoxicity ◽  
Cell Uptake ◽  
Solution Stability ◽  
T98g Cell ◽  
Human Glioblastoma Multiforme ◽  
Theranostic Agents ◽  
Uptake Studies

AbstractThe synthesis of a new series of Gd(III)-arylphosphonium complexes is described and the solution stability of selected compounds is reported. Their lipophilicity and uptake in human glial (SVG p12) and human glioblastoma multiforme (T98G) cell lines are presented. The in vitro cytotoxicity of all complexes was determined to be low at therapeutically-relevant concentrations. Selected Gd(III) complexes are potential candidates for further investigation as theranostic agents.

scholarly journals Simultaneous Exposure of Different Nanoparticles Influences Cell Uptake

Pharmaceutics ◽  
2022 ◽  
Vol 14 (1) ◽  
pp. 136
Author(s):  
Isa de Boer ◽  
Ceri J. Richards ◽  
Christoffer Åberg
Keyword(s):  
Drug Delivery ◽  
Individual Cell ◽  
Model System ◽  
Cell Uptake ◽  
Target Cells ◽  
Cell Level ◽  
Polystyrene Nanoparticles ◽  
Simultaneous Exposure ◽  
Different Types ◽  
Uptake Studies

Drug delivery using nano-sized carriers holds tremendous potential for curing a range of diseases. The internalisation of nanoparticles by cells, however, remains poorly understood, restricting the possibility for optimising entrance into target cells, avoiding off-target cells and evading clearance. The majority of nanoparticle cell uptake studies have been performed in the presence of only the particle of interest; here, we instead report measurements of uptake when the cells are exposed to two different types of nanoparticles at the same time. We used carboxylated polystyrene nanoparticles of two different sizes as a model system and exposed them to HeLa cells in the presence of a biomolecular corona. Using flow cytometry, we quantify the uptake at both average and individual cell level. Consistent with previous literature, we show that uptake of the larger particles is impeded in the presence of competing smaller particles and, conversely, that uptake of the smaller particles is promoted by competing larger particles. While the mechanism(s) underlying these observations remain(s) undetermined, we are partly able to restrain the likely possibilities. In the future, these effects could conceivably be used to enhance uptake of nano-sized particles used for drug delivery, by administering two different types of particles at the same time.

scholarly journals DNA with zwitterionic and negatively charged phosphate modifications: Formation of DNA triplexes, duplexes and cell uptake studies

2021 ◽  
Vol 17 ◽  
pp. 749-761
Author(s):  
Yongdong Su ◽  
Maitsetseg Bayarjargal ◽  
Tracy K Hale ◽  
Vyacheslav V Filichev
Keyword(s):  
Mouse Fibroblast ◽  
Cell Uptake ◽  
Dna Duplexes ◽  
Nih3t3 Cells ◽  
Dna Triplexes ◽  
Snake Venom Phosphodiesterase ◽  
Nuclease Digestion ◽  
Dna Backbone ◽  
Uptake Studies

Two phosphate modifications were introduced into the DNA backbone using the Staudinger reaction between the 3’,5’-dinucleoside β-cyanoethyl phosphite triester formed during DNA synthesis and sulfonyl azides, 4-(azidosulfonyl)-N,N,N-trimethylbutan-1-aminium iodide (N+ azide) or p-toluenesulfonyl (tosyl or Ts) azide, to provide either a zwitterionic phosphoramidate with N+ modification or a negatively charged phosphoramidate for Ts modification in the DNA sequence. The incorporation of these N+ and Ts modifications led to the formation of thermally stable parallel DNA triplexes, regardless of the number of modifications incorporated into the oligodeoxynucleotides (ONs). For both N+ and Ts-modified ONs, the antiparallel duplexes formed with complementary RNA were more stable than those formed with complementary DNA (except for ONs with modification in the middle of the sequence). Additionally, the incorporation of N+ modifications led to the formation of duplexes with a thermal stability that was less dependent on the ionic strength than native DNA duplexes. The thermodynamic analysis of the melting curves revealed that it is the reduction in unfavourable entropy, despite the decrease in favourable enthalpy, which is responsible for the stabilisation of duplexes with N+ modification. N+ONs also demonstrated greater resistance to nuclease digestion by snake venom phosphodiesterase I than the corresponding Ts-ONs. Cell uptake studies showed that Ts-ONs can enter the nucleus of mouse fibroblast NIH3T3 cells without any transfection reagent, whereas, N+ONs remain concentrated in vesicles within the cytoplasm. These results indicate that both N+ and Ts-modified ONs are promising for various in vivo applications.

scholarly journals Genetically designed biomolecular capping system for mesoporous silica nanoparticles enables receptor-mediated cell uptake and controlled drug release

Nanoscale ◽  
2016 ◽  
Vol 8 (15) ◽  
pp. 8101-8110 ◽  
Author(s):  
Stefan Datz ◽  
Christian Argyo ◽  
Michael Gattner ◽  
Veronika Weiss ◽  
Korbinian Brunner ◽  
...  
Keyword(s):  
Drug Release ◽  
Mesoporous Silica ◽  
Click Chemistry ◽  
Silica Nanoparticles ◽  
Mesoporous Silica Nanoparticles ◽  
Controlled Drug Release ◽  
Cell Uptake

We describe a novel enzyme-based cap system for mesoporous silica nanoparticles combined with bio-orthogonal click chemistry.

scholarly journals In Silico, in Vitro and in Vivo Investigation of a Newly Synthesized Ionic Compound As Anti-Alzheimer Multi-Target Dual AChE/BuChE Inhibitor Possessing Neuro-Protective Effects Against Aβ Induced Neurotoxicity in PC12 Cells and Alzheimer Rat Model

2021 ◽  
Author(s):  
Hosna Karami ◽  
somaieh soltani ◽  
Gerhard Wolber ◽  
Saeed Sadigh-Eteghad ◽  
Roghaye Nikbakht ◽  
...  
Keyword(s):  
Pc12 Cells ◽  
Quaternary Ammonium ◽  
Aqueous Solubility ◽  
In Vivo Studies ◽  
Protective Effects ◽  
Rat Models ◽  
Tnf Α ◽  
Neuro Inflammation

Abstract Multi-target anti Alzheimer’s disease (AD) compounds are promising leads for the development of AD modifying agents. Ionic compounds containing quaternary ammonium moiety were synthesized and their multi-targeted anti-AD effects were examined in the current study. Compound 5g possessed suitable aqueous solubility and cell toxicity. It also showed non-competitive dual hAChE/hBuChE inhibition activity. Compound 5g reversed the Aβ-treated PC12 cells’ morphology alteration and reduced PC12 cells’ death. Compound 5g possessed anti-oxidative stress activity through anti-oxidant, anti-ROS production and anti-lipid peroxidation mechanisms. It also reduced the expression of IL-1β and TNF-α genes. Furthermore, compound 5g LDH inhibition, reduction of neuro-inflammation and prevention of autophagy-apoptosis were approved by the results of in vitro studies. Compound 5g delivery to brain was confirmed by in vivo studies. Administration of compound 5g to Aβ-induced AD rat models improved their cognition function and spatial memory learning behavior. TNF-α and NFkB down-regulated in compound 5g treated AD rats’ hippocamp. Besides, compound 5g reversed the up-regulation of AChE in Aβ treated rats’ hippocamp. Molecular modeling studies confirmed the interaction of compound 5g with both steric and catalytic sites of ChE enzymes. The newly synthesized quaternary ammonium containing derivative (compound 5g) possessed multi-target anti-AD efficacy based on in vitro and in vivo studies and its efficacy in AD rat models were approved by behavioral and molecular investigations.

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