scholarly journals Dendrimer-Functionalized Hybrid Materials Based on Silica as Novel Carriers of Bioactive Acids

Molecules ◽  
2020 ◽  
Vol 25 (11) ◽  
pp. 2660
Author(s):  
Mateusz Pawlaczyk ◽  
Grzegorz Schroeder

One of the major goals in the materials science is the design and development of non-toxic, versatile, and efficient drug delivery systems. The study reported in this paper concerns the syntheses of poly(amidoamine) (PAMAM) dendrimers with tris(2-aminoethyl)amine as an amine core and different terminal amines, and their attachment to silica matrix. The obtained ethylenediamine (EDA), triethylenetetramine (TETA), tris(2-aminoethyl)amine (TREN) and 4,7,10-trioxa-1,13-tridecanediamine (TRI-OXA) dendrimers were introduced to the support surface via an epoxy linker, leading to a loading efficiency in the range of 0.054–0.113 mmol g−1, determined using elemental and thermogravimetric analyses. The materials exhibited high adsorption capacities towards the chosen model drugs: folic, salicylic and nicotinic acid. The investigated adsorption processes were found to follow the Freundlich isotherm model, with indication of the drugs’ structure influence on the binding efficiency. Drug-loaded hybrid materials were also described for in vitro drug release in three pH-different paraphysiological media. The highest percentage release was obtained in the tests performed at pH 2.0, ranging between 35.42 and 99.83%. Satisfactory results and the versatility of PAMAM dendrimers may lead to the application of such materials not only as drug carriers dedicated to a wide range of pharmaceutics, but also as analytical tools for pre-concentration and/or the determination of biocompound contamination in samples.

2021 ◽  
Author(s):  
Tasrina Munmun ◽  
Arif Md. Rashedul Kabir ◽  
Kazuki Sada ◽  
Akira Kakugo

AbstractWe demonstrate that the rigidity of the microtubules (MTs), propelled by kinesins in an in vitro gliding assay, can be modulated using the deep-sea osmolyte trimethylamine N-oxide (TMAO). By varying the concentration of TMAO in the gliding assay, the rigidity of the MTs is modulated over a wide range. By employing this approach, we are able to reduce the persistence length of MTs, a measure of MT rigidity, ∼8 fold using TMAO of the concentration of 1.5 M. The rigidity of gliding MTs can be restored by eliminating the TMAO from the gliding assay. This work offers a simple strategy to regulate the rigidity of kinesin-propelled MTs in situ and would widen the applications of biomolecular motors in nanotechnology, materials science, and bioengineering.


Nanomaterials ◽  
2019 ◽  
Vol 9 (2) ◽  
pp. 147 ◽  
Author(s):  
Huichao Xie ◽  
Lingjun Li ◽  
Yue Sun ◽  
Yuzhen Wang ◽  
Shuang Gao ◽  
...  

Polyamidoamine (PAMAM) dendrimers are efficient drug carriers. The presence of a physiological pathway for nasal brain transport provides a potential path for direct brain-targeted delivery of dendrimer nanocomposites. In this study, we synthesized PAMAM dendrimer composites with a nanoscale size; the particle size of PAE (Paeonol)/mPEG (the heterofunctional PEG polymer with a methoxy)-PAMAM G5.NHAc and mPEG-PAMAM G5.NH2-FITC were 72.41 ± 11.58 nm and 96.51 ± 7.77 nm, and the zeta potential of PAE/mPEG-PAMAM G5.NHAc and mPEG-PAMAM G5.NH2-FITC were + 0.57 ± 0.11 mv and + 9.60 ± 0.41 mv, respectively. The EE% and DL% of PAE in PAE/mPEG-PAMAM G5.NHAc were 53.77% and 13.92%, respectively. PAE/mPEG-PAMAM G5.NHAc/DGG ionic-sensitive in situ gel was prepared, the viscosity of solution and gel state were 112 ± 3.2 mPa and 1403 ± 38.5 mPa, respectively. The in vitro goat mucoadhesive strength of the gel was 4763.36 ± 85.39 dyne/cm2. In situ gel system was proven to be a non-Newtonian pseudo-plastic fluid with shear thinning, thixotropy and yield stress. The optimal model of PAE released from PAE/mPEG-PAMAM G5.NHAc and PAE/mPEG-PAMAM G5.NHAc/DGG were the Higuchi equation and the Korsmeyer-Peppas equation, respectively. The cytotoxicity of the nanocomposites showed a concentration-dependence, and the cell viabilities of PAE/mPEG-PAMAM G5.NHAc were both higher than 95% between 0.0001 μM and 10 μM. mPEG-PAMAM G5.NH2-FITC was efficiently taken up by cells and exhibited strong fluorescence in the cytoplasm and nucleus. Significant accumulation of nanocomposites was observed in the brain after administration of the in situ gel group, and maximum accumulation was reached at 12 h. A small amount of accumulation was observed in the nanocomposite solution group only at 2 h. Therefore, the direct nasal brain transport efficiency of PAMAM dendrimer nanocomposites can be significantly improved after combining with in situ gel. PAMAM dendrimer nanocomposite/DGG is a potential drug delivery system for nasal brain transport.


Author(s):  
Maria Camilla Operti ◽  
Yusuf Dölen ◽  
Jibbe Keulen ◽  
Eric A.W. van Dinther ◽  
Carl G. Figdor ◽  
...  

Polymeric particles made up of biodegradable and biocompatible polymers such as poly(lactic-co-glycolic acid) (PLGA) are promising tools for several biomedical applications including drug delivery. Particular emphasis is placed on the size and surface functionality of these systems as they are regarded as the main protagonists in dictating the particle behavior in vitro and in vivo. Current methods of manufacturing polymeric drug carriers offer a wide range of achievable particle sizes, however, they are unlikely to accurately control the size while maintaining the same production method and particle uniformity, as well as final production yield. Microfluidics technology has emerged as an efficient tool to manufacture particles in a highly controllable manner. Here, we report on tuning the size of PLGA particles at diameters ranging from sub-micron to microns using a single microfluidics device, and demonstrate how particle size influences the release characteristics, cellular uptake and in vivo clearance of these particles. Highly controlled production of PLGA particles with ~100 nm, ~200 nm and >1000 nm diameter is achieved through modification of flow and formulation parameters. Efficiency of particle uptake by dendritic cells and myeloid-derived suppressor cells isolated from mice is strongly correlated with particle size and is most efficient for ~100 nm particles. Particles systemically administered to mice mainly accumulate in liver and ~100 nm particles are cleared slower. Our study shows the direct relation between the particle size varied through microfluidics and the pharmacokinetics behavior of particles, which provides a further step towards the establishment of a customizable production process to generate tailor-made nanomedicines.


2014 ◽  
Vol 136 (12) ◽  
Author(s):  
Salman Sohrabi ◽  
Junda Zheng ◽  
Ender A. Finol ◽  
Yaling Liu

To quantify the transport and adhesion of drug particles in a complex vascular environment, computational fluid particle dynamics (CFPD) simulations of blood flow and drug particulate were conducted in three different geometries representing the human lung vasculature for steady and pulsatile flow conditions. A fully developed flow profile was assumed as the inlet velocity, and a lumped mathematical model was used for the calculation of the outlet pressure boundary condition. A receptor–ligand model was used to simulate the particle binding probability. The results indicate that bigger particles have lower deposition fraction due to less chance of successful binding. Realistic unsteady flow significantly accelerates the binding activity over a wide range of particle sizes and also improves the particle deposition fraction in bifurcation regions when comparing with steady flow condition. Furthermore, surface imperfections and geometrical complexity coupled with the pulsatility effect can enhance fluid mixing and accordingly particle binding efficiency. The particle binding density at bifurcation regions increases with generation order and drug carriers are washed away faster in steady flow. Thus, when studying drug delivery mechanism in vitro and in vivo, it is important to take into account blood flow pulsatility in realistic geometry. Moreover, tissues close to bifurcations are more susceptible to deterioration due to higher uptake.


2020 ◽  
Vol 17 (169) ◽  
pp. 20200510
Author(s):  
Mark Epshtein ◽  
Netanel Korin

Intracranial aneurysms frequently develop blood clots, plaque and inflammations, which are linked to enhanced particulate mass deposition. In this work, we propose a computational model for particulate deposition, that accounts for the influence of field forces, such as gravity and electrostatics, which produce an additional flux of particles perpendicular to the fluid motion and towards the wall. This field-mediated flux can significantly enhance particle deposition in low-shear environments, such as in aneurysm cavities. Experimental investigation of particle deposition patterns in in vitro models of side aneurysms, demonstrated the ability of the model to predict enhanced particle adhesion at these sites. Our results showed a significant influence of gravity and electrostatic forces (greater than 10%), indicating that the additional terms presented in our models may be necessary for modelling a wide range of physiological flow conditions and not only for ultra-low shear regions. Spatial differences between the computational model and the experimental results suggested that additional transport and fluidic mechanisms affect the deposition pattern within aneurysms. Taken together, the presented findings may enhance our understanding of pathological deposition processes at cardiovascular disease sites, and facilitate rational design and optimization of cardiovascular particulate drug carriers.


Author(s):  
Chrysanthi-Maria Moysidou ◽  
Róisín M. Owens

The human gut microbiome has emerged as a key player in the bidirectional communication of the gut–brain axis, affecting various aspects of homeostasis and pathophysiology. Until recently, the majority of studies that seek to explore the mechanisms underlying the microbiome–gut–brain axis cross-talk, relied almost exclusively on animal models, and particularly gnotobiotic mice. Despite the great progress made with these models, various limitations, including ethical considerations and interspecies differences that limit the translatability of data to human systems, pushed researchers to seek for alternatives. Over the past decades, the field of in vitro modelling of tissues has experienced tremendous growth, thanks to advances in 3D cell biology, materials, science and bioengineering, pushing further the borders of our ability to more faithfully emulate the in vivo situation. The discovery of stem cells has offered a new source of cells, while their use in generating gastrointestinal and brain organoids, among other tissues, has enabled the development of novel 3D tissues that better mimic the native tissue structure and function, compared with traditional assays. In parallel, organs-on-chips technology and bioengineered tissues have emerged as highly promising alternatives to animal models for a wide range of applications. Here, we discuss how recent advances and trends in this area can be applied in host–microbe and host–pathogen interaction studies. In addition, we highlight paradigm shifts in engineering more robust human microbiome-gut-brain axis models and their potential to expand our understanding of this complex system and hence explore novel, microbiome-based therapeutic approaches.


Pharmaceutics ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 590 ◽  
Author(s):  
Maria Camilla Operti ◽  
Yusuf Dölen ◽  
Jibbe Keulen ◽  
Eric A. W. van Dinther ◽  
Carl G. Figdor ◽  
...  

Polymeric particles made up of biodegradable and biocompatible polymers such as poly(lactic-co-glycolic acid) (PLGA) are promising tools for several biomedical applications including drug delivery. Particular emphasis is placed on the size and surface functionality of these systems as they are regarded as the main protagonists in dictating the particle behavior in vitro and in vivo. Current methods of manufacturing polymeric drug carriers offer a wide range of achievable particle sizes, however, they are unlikely to accurately control the size while maintaining the same production method and particle uniformity, as well as final production yield. Microfluidics technology has emerged as an efficient tool to manufacture particles in a highly controllable manner. Here, we report on tuning the size of PLGA particles at diameters ranging from sub-micron to microns using a single microfluidics device, and demonstrate how particle size influences the release characteristics, cellular uptake and in vivo clearance of these particles. Highly controlled production of PLGA particles with ~100 nm, ~200 nm, and >1000 nm diameter is achieved through modification of flow and formulation parameters. Efficiency of particle uptake by dendritic cells and myeloid-derived suppressor cells isolated from mice is strongly correlated with particle size and is most efficient for ~100 nm particles. Particles systemically administered to mice mainly accumulate in liver and ~100 nm particles are cleared slower. Our study shows the direct relation between particle size varied through microfluidics and the pharmacokinetics behavior of particles, which provides a further step towards the establishment of a customizable production process to generate tailor-made nanomedicines.


1991 ◽  
Vol 30 (01) ◽  
pp. 35-39 ◽  
Author(s):  
H. S. Durak ◽  
M. Kitapgi ◽  
B. E. Caner ◽  
R. Senekowitsch ◽  
M. T. Ercan

Vitamin K4 was labelled with 99mTc with an efficiency higher than 97%. The compound was stable up to 24 h at room temperature, and its biodistribution in NMRI mice indicated its in vivo stability. Blood radioactivity levels were high over a wide range. 10% of the injected activity remained in blood after 24 h. Excretion was mostly via kidneys. Only the liver and kidneys concentrated appreciable amounts of radioactivity. Testis/soft tissue ratios were 1.4 and 1.57 at 6 and 24 h, respectively. Testis/blood ratios were lower than 1. In vitro studies with mouse blood indicated that 33.9 ±9.6% of the radioactivity was associated with RBCs; it was washed out almost completely with saline. Protein binding was 28.7 ±6.3% as determined by TCA precipitation. Blood clearance of 99mTc-l<4 in normal subjects showed a slow decrease of radioactivity, reaching a plateau after 16 h at 20% of the injected activity. In scintigraphic images in men the testes could be well visualized. The right/left testis ratio was 1.08 ±0.13. Testis/soft tissue and testis/blood activity ratios were highest at 3 h. These ratios were higher than those obtained with pertechnetate at 20 min post injection.99mTc-l<4 appears to be a promising radiopharmaceutical for the scintigraphic visualization of testes.


1997 ◽  
Vol 77 (04) ◽  
pp. 725-729 ◽  
Author(s):  
Mario Colucci ◽  
Silvia Scopece ◽  
Antonio V Gelato ◽  
Donato Dimonte ◽  
Nicola Semeraro

SummaryUsing an in vitro model of clot lysis, the individual response to a pharmacological concentration of recombinant tissue plasminogen activator (rt-PA) and the influence on this response of the physiological variations of blood parameters known to interfere with the fibrinolytic/thrombolytic process were investigated in 103 healthy donors. 125I-fibrin labelled blood clots were submersed in autologous plasma, supplemented with 500 ng/ml of rt-PA or solvent, and the degree of lysis was determined after 3 h of incubation at 37° C. Baseline plasma levels of t-PA, plasminogen activator inhibitor 1 (PAI-1), plasminogen, α2-anti-plasmin, fibrinogen, lipoprotein (a), thrombomodulin and von Willebrand factor as well as platelet and leukocyte count and clot retraction were also determined in each donor. rt-PA-induced clot lysis varied over a wide range (28-75%) and was significantly related to endogenous t-PA, PAI-1, plasminogen (p <0.001) and age (p <0.01). Multivariate analysis indicated that both PAI-1 antigen and plasminogen independently predicted low response to rt-PA. Surprisingly, however, not only PAI-1 but also plasminogen was negatively correlated with rt-PA-ginduced clot lysis. The observation that neutralization of PAI-1 by specific antibodies, both in plasma and within the clot, did not potentiate clot lysis indicates that the inhibitor, including the platelet-derived form, is insufficient to attenuate the thrombolytic activity of a pharmacological concentration of rt-PA and that its elevation, similarly to the elevation of plasminogen, is not the cause of clot resistance but rather a coincident finding. It is concluded that the in vitro response of blood clots to rt-PA is poorly influenced by the physiological variations of the examined parameters and that factors other than those evaluated in this study interfere with clot dissolution by rt-PA. In vitro clot lysis test might help to identify patients who may be resistant to thrombolytic therapy.


Growth regulators, phytohormones, both natural and artificial, are the main means to control plant ontogenesis. They are involved in regulating the processes of cell differentiation and cell divisions, the formation of tissues and organs, the changes in the rate of growth and development, the duration of the certain stages of ontogenesis. The main classes of phytohormones used in plant biotechnology, in particular, in the induction of haploid structures, are auxins and cytokinins. The mechanism of action of phytohormones on a cell is rather complicated and may have a different character. Understanding the characteristics of the action of phytohormones is complicated by the fact that the system of hormonal regulation of plant life is multicomponent. This is manifested in the fact that the same physiological process is most often influenced not by one, but by several phytohormones, covering a wide range of aspects of cell metabolism. In connection with the foregoing, the purpose of our work was to test a set of nutrient media with different basic composition and different proportions of phytohormones to determine the patterns of their influence on the processes of haploid structure induction in rape anther culture using accessions, developed at the Institute of Oilseed Crops NAAS. The material used was two accessions of winter rapeseed (No. 1 and No. 2) and one sample of spring rapeseed, provided by the Rapeseed Breeding laboratory of the Institute of Oilseed Crops. Incised inflorescences were kept against the background of low temperature of 6–8 ° C for several days, and then, under aseptic conditions, anthers with unripe pollen grains were isolated and planted on nutrient media differing in both basic mineral composition and content of phytohormones. MS (Murashige & Skoog 1962) and B5 (Gamborg et al 1968) media were used as basic media. Phytohormones were added to the basic media in various combinations – BA, 2,4-D, NAA at the concentrations of 0.1-0.6 mg/l. In each treatment up to 300 anthers were cultivated. Differences between treatments were evaluated using standard t-test. Studies have shown that in the anther culture of rapeseed on the tested nutrient media, morphogenic structures of different types (embryoids and callus) were originated. Synthetic auxin 2,4-D, regardless of the composition of the basic medium, caused the formation of structures of both types, though with a low frequency. Phytohormone BA of the cytokinin type had a similar effect. In this case, the frequency of structures was slightly higher, and the developed structures were represented mainly by embryoids. The joint action of cytokinin and auxin was the most favorable for the initiation of morphogenic structures. Such combination of phytohormones caused the formation of these structures with a frequency of 24.5-14.7% in the studied genotypes of winter rape. A similar effect of phytohormones on the induction and development of morphogenic structures was also observed in spring rape. In this case, a single basic MS medium was used. The experiment included treatments where phytohormones were absent (control), as well as various combinations of auxin and cytokinin. In the control treatment, the formation of new structures was not noted. In treatments with phytohormones, in addition to the medium with the combination of auxin and cytokinin, the medium in which only cytokinin was present was also rather effective. The treatment in which the action of auxin 2,4-D was combined with the action of another auxin, NAA, turned out to be practically ineffective. Thus, it was found that for the induction of morphogenic structures from microspores in rape anther culture of the tested genotypes, the combination of cytokinin with auxin, or the use of only single cytokinin BA without other phytohormones, had the most positive effect.


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