The aspect ratio effect of drug nanocrystals on cellular internalization efficiency, uptake mechanisms, and in vitro and in vivo anticancer efficiencies

Nanoscale ◽  
2015 ◽  
Vol 7 (8) ◽  
pp. 3588-3593 ◽  
Author(s):  
Baishun Tian ◽  
Xiujuan Zhang ◽  
Caitong Yu ◽  
Mengjiao Zhou ◽  
Xiaohong Zhang

The aspect ratio effect of drug nanocrystals on their in vitro cellular internalizing efficiency and in vivo antitumor efficiency was investigated.

2021 ◽  
Vol 10 (3) ◽  
pp. 2825-2831
Author(s):  
Rijawan Rajjak Pathan

Pellets formulation with natural gums. The formulation of an enzyme as well as pH dependant pellets containing natural gums such as Mornings oleifera gum Lam. (MOG) and Cyamopsis tetragonolobus gum Taub. (CTG) were used for enzyme dependant release and further coating is provided to shows colon-specific delivery. Extrusion and spheronization techniques were used for the preparation of pellets. Pellets of budesonide evaluated for various properties such as flow behavior, physical properties such as sphericity, roundness, aspect ratio, hardness, and friability also investigated in vitro and in vivo targeting in rabbit. Preparation of pellets was done by using extrusion and spheronization method with the use of optimized concentration of gums those were 7.5% and 10% for CTG and MOG respectively and proportion of solvent mixture of water and Isopropyl alcohol in the ratio of 80:20. Pellets of budesonide evaluated for various properties includes flow behavior, physical properties such as sphericity, roundness, aspect ratio, hardness, and friability and found that all properties as per official limit also in vitro release study found that release of uncoated pellets in a sustained manner in 0.1N HCl for 2h due to swelling of natural gum, therefore further step of the coating was done in fluidized bed coater to prevent the release of drug in the upper part of GIT and after coating found that In vitro release of drug at the colonic environment and it confirmed with in vivo investigation in rabbit with X-ray examination of targeting and found that pellets reach at colonic part without disintegration. The use of natural gums for preparation of pellets in optimized concentration and wetting agent produce a formulation with all required chemical and physical properties and it gives effective in vitro release and also shows In vivo targeting in rabbit and due to use of natural gum for preparation of pellets also reduce some problems of metabolism of synthetic excipients.


2018 ◽  
Vol 33 (6) ◽  
pp. 660-675
Author(s):  
Gwang Jin Noh ◽  
Hongsuk Park ◽  
Eun Seong Lee

Gold nanoparticles with various functionalities have served as potential tools in nanotechnology for tumor ablation. In this work, we seek to design and develop gold nanoparticle with poly(ethylene glycol)-containing dopamine (hereafter termed as AuND), and to synthesize the AuND with one-sided Tat peptide expression (OT@AuND). We demonstrate the tumor cell-targeting ability on the basis of anti-nonspecific cell binding of OT@AuND and determine how the chemically modified gold nanoparticle–based product affects photothermal tumor therapy in vitro and in vivo. The OT@AuND with a particular cellular entry orientation–induced delayed endocytosis, which is advantageous for enhanced permeability and retention effect-based tumor accumulation. This is because the slower cellular interaction of OT@AuND allows it to have the time to be transported to and bind to the tumor site. In tumor cell lines, OT@AuND showed a lower cellular uptake than gold nanoparticles with full-sided Tat peptide expression (FT@AuND) in the early period (after its in vitro and in vivo administration), but the cellular internalization rate of OT@AuND caught up with that of FT@AuND in the late period. Importantly, the delayed cellular internalization feature of OT@AuND resulted in efficient tumor accumulation in tumor-bearing mice, because the time interval provided OT@AuND more chances not to bind to any cells, but to enter tumor cells, leading to selective photothermal tumor ablation. These data suggest that gold nanoparticles with a particular cellular entry orientation can be further explored as a potential photothermal therapeutic agent and as a strategy to treat tumors.


Author(s):  
D Bennett ◽  
J F Orr ◽  
D E Beverland ◽  
R Baker

Wear of the polyethylene acetabular component is the most serious threat to the long-term success of total hip replacements (THRs). Greatly reduced wear rates have been reported for unidirectional, compared to multidirectional, articulation in vitro. This study considers the multidirectional motions experienced at the hip joint as described by movement loci of points on the femoral head for individual THR patients. A three-dimensional computer program determined the movement loci of selected points on the femoral head for THR patients and normal subjects using kinematic data obtained from gait analysis. The sizes and shapes of these loci were quantified by their sliding distances and aspect ratios with substantial differences exhibited between individual THR patients. The average sliding distances ranged from 10.0 to 18.1 mm and the average aspect ratios of the loci ranged from 2.5 to 9.2 for the THR patients. Positive correlations were found between wear rate and average sliding distance, the inverse of the average aspect ratio of the loci and the product of the average sliding distance and the inverse of the average aspect ratio of the loci. Patients with a normal hip joint range of motion produce multidirectional motion loci and tend to experience more wear than patients with more unidirectional motion loci. Differing patterns of multidirectional motion at the hip joint for individual THR patients may explain widely differing wear rates in vivo.


Materials ◽  
2020 ◽  
Vol 13 (2) ◽  
pp. 366 ◽  
Author(s):  
Levi Collin Nelemans ◽  
Leonid Gurevich

Nanocarrier-based systems hold a promise to become “Dr. Ehrlich’s Magic Bullet” capable of delivering drugs, proteins and genetic materials intact to a specific location in an organism down to subcellular level. The key question, however, how a nanocarrier is internalized by cells and how its intracellular trafficking and the fate in the cell can be controlled remains yet to be answered. In this review we survey drug delivery systems based on various polymeric nanocarriers, their uptake mechanisms, as well as the experimental techniques and common pathway inhibitors applied for internalization studies. While energy-dependent endocytosis is observed as the main uptake pathway, the integrity of a drug-loaded nanocarrier upon its internalization appears to be a seldomly addressed problem that can drastically affect the uptake kinetics and toxicity of the system in vitro and in vivo.


1978 ◽  
Vol 52 (3-4) ◽  
pp. 367-374 ◽  
Author(s):  
Thomas P. Blackburn ◽  
George A. Foster ◽  
David T. Greenwood ◽  
Ralph Howe

2019 ◽  
Vol 17 (1) ◽  
Author(s):  
Edouard Alphandéry ◽  
Ahmed Idbaih ◽  
Clovis Adam ◽  
Jean-Yves Delattre ◽  
Charlotte Schmitt ◽  
...  

Abstract Background An important but rarely addressed question in nano-therapy is to know whether bio-degraded nanoparticles with reduced sizes and weakened heating power are able to maintain sufficient anti-tumor activity to fully eradicate a tumor, hence preventing tumor re-growth. To answer it, we studied magnetosomes, which are nanoparticles synthesized by magnetotactic bacteria with sufficiently large sizes (~ 30 nm on average) to enable a follow-up of nanoparticle sizes/heating power variations under two different altering conditions that do not prevent anti-tumor activity, i.e. in vitro cellular internalization and in vivo intra-tumor stay for more than 30 days. Results When magnetosomes are internalized in U87-Luc cells by being incubated with these cells during 24 h in vitro, the dominant magnetosome sizes within the magnetosome size distribution (DMS) and specific absorption rate (SAR) strongly decrease from DMS ~ 40 nm and SAR ~ 1234 W/gFe before internalization to DMS ~ 11 nm and SAR ~ 57 W/gFe after internalization, a behavior that does not prevent internalized magnetosomes to efficiently destroy U87-Luc cell, i.e. the percentage of U87-Luc living cells incubated with magnetosomes decreases by 25% between before and after alternating magnetic field (AMF) application. When 2 µl of a suspension containing 40 µg of magnetosomes are administered to intracranial U87-Luc tumors of 2 mm3 and exposed (or not) to 15 magnetic sessions (MS), each one consisting in 30 min application of an AMF of 27 mT and 198 kHz, DMS and SAR decrease between before and after the 15 MS from ~ 40 nm and ~ 4 W/gFe down to ~ 29 nm and ~ 0 W/gFe. Although the magnetosome heating power is weakened in vivo, i.e. no measurable tumor temperature increase is observed after the sixth MS, anti-tumor activity remains persistent up to the 15th MS, resulting in full tumor disappearance among 50% of treated mice. Conclusion Here, we report sustained magnetosome anti-tumor activity under conditions of significant magnetosome size reduction and complete loss of magnetosome heating power.


Small ◽  
2019 ◽  
Vol 15 (42) ◽  
pp. 1901642 ◽  
Author(s):  
Xiang Wang ◽  
Chong Hyun Chang ◽  
Jinhong Jiang ◽  
Qi Liu ◽  
Yu‐Pei Liao ◽  
...  

2015 ◽  
Vol 5 (1) ◽  
Author(s):  
Jiali Wan ◽  
Jia-Hong Wang ◽  
Ting Liu ◽  
Zhixiong Xie ◽  
Xue-Feng Yu ◽  
...  

RSC Advances ◽  
2014 ◽  
Vol 4 (107) ◽  
pp. 62708-62716 ◽  
Author(s):  
F. R. Cheng ◽  
Y. J. Yang ◽  
Y. Liang ◽  
J. Q. Yan ◽  
J. Cao ◽  
...  

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