‘Adhesion and release’ nanoparticle-mediated efficient inhibition of platelet activation disrupts endothelial barriers for enhanced drug delivery in tumors

Biomaterials ◽  
2021 ◽  
Vol 269 ◽  
pp. 120620
Author(s):  
Jinxu Cao ◽  
Peng Yang ◽  
Pengzhen Wang ◽  
Shuting Xu ◽  
Yunlong Cheng ◽  
...  
2005 ◽  
Vol 93 (01) ◽  
pp. 106-114 ◽  
Author(s):  
Anirban Gupta ◽  
Guofeng Huang ◽  
Brian Lestini ◽  
Sharon Sagnella ◽  
Kandice Kottke-Marchant ◽  
...  

SummaryLocal drug delivery has become an important treatment modality for the prevention of thrombotic events following coronary angioplasty. In this study, we investigate the ability of liposomes bearing surface conjugated linear Arg-Gly-Asp (RGD) peptide (GSSSGRGD SPA) moieties to target and bind activated platelets, and the effect of such RGD-modified liposomes on platelet activation and aggregation. The binding of RGD-liposomes to human platelets was assessed by fluorescence microscopy,phase contrast microscopy and flow cytometry. The effect of RGDmodified liposomes on platelet activation and aggregation was investigated in vitro, with and without platelet agonists. RGD-liposomes were found to bind activated platelets at levels significantly greater than the control RGE-liposomes.The RGD-liposomes did not exhibit any statistically significant effect on platelet activation or aggregation.The results demonstrate the ability of the RGD-modified liposomes to target and bind activated platelets without causing significant platelet aggregation and suggests a feasible way for the development of a platelet-targeted anti-thrombogenic drug delivery system. Furthermore, the approach can be extended to the development of liposomes for other vascular targets, for application in drug delivery or gene therapy.


Author(s):  
G.E. Visscher ◽  
R. L. Robison ◽  
G. J. Argentieri

The use of various bioerodable polymers as drug delivery systems has gained considerable interest in recent years. Among some of the shapes used as delivery systems are films, rods and microcapsules. The work presented here will deal with the techniques we have utilized for the analysis of the tissue reaction to and actual biodegradation of injectable microcapsules. This work has utilized light microscopic (LM), transmission (TEM) and scanning (SEM) electron microscopic techniques. The design of our studies has utilized methodology that would; 1. best characterize the actual degradation process without artifacts introduced by fixation procedures and 2. allow for reproducible results.In our studies, the gastrocnemius muscle of the rat was chosen as the injection site. Prior to the injection of microcapsules the skin above the sites was shaved and tattooed for later recognition and recovery. 1.0 cc syringes were loaded with the desired quantity of microcapsules and the vehicle (0.5% hydroxypropylmethycellulose) drawn up. The syringes were agitated to suspend the microcapsules in the injection vehicle.


Author(s):  
D.J.P. Ferguson ◽  
M. Virji ◽  
H. Kayhty ◽  
E.R. Moxon

Haemophilus influenzae is a human pathogen which causes meningitis in children. Systemic H. influenzae infection is largely confined to encapsulated serotype b organisms and is a major cause of meningitis in the U.K. and elsewhere. However, the pathogenesis of the disease is still poorly understood. Studies in the infant rat model, in which intranasal challenge results in bacteraemia, have shown that H. influenzae enters submucosal tissues and disseminates to the blood stream within minutes. The rapidity of these events suggests that H. influenzae penetrates both respiratory epithelial and endothelial barriers with great efficiency. It is not known whether the bacteria penetrate via the intercellular junctions, are translocated within the cells or carried across the cellular barrier in 'trojan horse' fashion within phagocytes. In the present studies, we have challenged cultured human umbilical cord_vein endothelial cells (HUVECs) with both capsulated (b+) and capsule-deficient (b-) isogenic variants of one strain of H. influenzae in order to investigate the interaction between the bacteria and HUVEC and the effect of the capsule.


2010 ◽  
Vol 34 (8) ◽  
pp. S33-S33
Author(s):  
Wenchao Ou ◽  
Haifeng Chen ◽  
Yun Zhong ◽  
Benrong Liu ◽  
Keji Chen

2020 ◽  
Vol 4 (6) ◽  
pp. 645-675
Author(s):  
Parasuraman Padmanabhan ◽  
Mathangi Palanivel ◽  
Ajay Kumar ◽  
Domokos Máthé ◽  
George K. Radda ◽  
...  

Neurodegenerative diseases (NDDs), including Alzheimer's disease (AD) and Parkinson's disease (PD), affect the ageing population worldwide and while severely impairing the quality of life of millions, they also cause a massive economic burden to countries with progressively ageing populations. Parallel with the search for biomarkers for early detection and prediction, the pursuit for therapeutic approaches has become growingly intensive in recent years. Various prospective therapeutic approaches have been explored with an emphasis on early prevention and protection, including, but not limited to, gene therapy, stem cell therapy, immunotherapy and radiotherapy. Many pharmacological interventions have proved to be promising novel avenues, but successful applications are often hampered by the poor delivery of the therapeutics across the blood-brain-barrier (BBB). To overcome this challenge, nanoparticle (NP)-mediated drug delivery has been considered as a promising option, as NP-based drug delivery systems can be functionalized to target specific cell surface receptors and to achieve controlled and long-term release of therapeutics to the target tissue. The usefulness of NPs for loading and delivering of drugs has been extensively studied in the context of NDDs, and their biological efficacy has been demonstrated in numerous preclinical animal models. Efforts have also been made towards the development of NPs which can be used for targeting the BBB and various cell types in the brain. The main focus of this review is to briefly discuss the advantages of functionalized NPs as promising theranostic agents for the diagnosis and therapy of NDDs. We also summarize the results of diverse studies that specifically investigated the usage of different NPs for the treatment of NDDs, with a specific emphasis on AD and PD, and the associated pathophysiological changes. Finally, we offer perspectives on the existing challenges of using NPs as theranostic agents and possible futuristic approaches to improve them.


2001 ◽  
Vol 120 (5) ◽  
pp. A670-A670
Author(s):  
M NERI ◽  
G DAVI ◽  
D FESTI ◽  
F LATERZA ◽  
A FALCO ◽  
...  

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