Bioanalysis of Targeted Nanoparticles in Monkey Plasma via LC-MS/MS

2019 ◽  
Vol 91 (21) ◽  
pp. 13874-13882 ◽  
Author(s):  
Wei Song ◽  
Joseph A. Tweed ◽  
Ravi Visswanathan ◽  
James P. Saunders ◽  
Zhenhua Gu ◽  
...  
2014 ◽  
Vol 21 (36) ◽  
pp. 4092-4099 ◽  
Author(s):  
A. Burkhart ◽  
M. Azizi ◽  
M.S. Thomsen ◽  
L.B. Thomsen ◽  
T. Moos

Author(s):  
Ajita Bhatt ◽  
Ekta Gurnany ◽  
Anuj Modi ◽  
Arvind Gulbake ◽  
Aviral Jain

2020 ◽  
Vol 20 (16) ◽  
pp. 1966-1980
Author(s):  
Jaleh Varshosaz ◽  
Saeedeh Fardshouraki ◽  
Mina Mirian ◽  
Leila Safaeian ◽  
Setareh Jandaghian ◽  
...  

Background: Using imatinib, a tyrosine kinase inhibitor drug used in lymphoblastic leukemia, has always had limitations due to its cardiotoxicity and hepatotoxicity side effects. The objective of this study is to develop a target-oriented drug carrier to minimize these adverse effects by the controlled release of the drug. Methods: KIT-5 nanoparticles were functionalized with 3-aminopropyltriethoxysilane and conjugated to rituximab as the targeting agent for the CD20 positive receptors of the B-cells. Then they were loaded with imatinib and their physical properties were characterized. The cell cytotoxicity of the nanoparticles was studied by MTT assay in Ramos (CD20 positive) and Jurkat cell lines (CD20 negative) and their cellular uptake was shown by fluorescence microscope. Wistar rats received an intraperitoneal injection of 50 mg/kg of the free drug or targeted nanoparticles for 21 days. Then the level of aspartate Aminotransferase (AST), alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP) and Lactate Dehydrogenase (LDH) were measured in serum of animals. The cardiotoxicity and hepatotoxicity of the drug were also studied by hematoxylin and eosin staining of the tissues. Results: The targeted nanoparticles of imatinib showed to be more cytotoxic to Ramos cells rather than Jurkat cells. The results of the biochemical analysis displayed a significant reduction in AST, ALT, ALP, and LDH levels in animals treated with targeted nanoparticles, compared to the free drug group. By comparison with the free imatinib, histopathological results represented less cardiotoxicity and hepatotoxicity in the animals, which received the drug through the current designed delivery system. Conclusion: The obtained results confirmed that the rituximab targeted KIT-5 nanoparticles are promising in the controlled release of imatinib and could decrease its cardiotoxicity and hepatotoxicity side effects.


2021 ◽  
Vol 63 ◽  
pp. 102543
Author(s):  
Borhaneh Hasan-Nasab ◽  
Pedram Ebrahimnejad ◽  
Pouneh Ebrahimi ◽  
Faezeh Sharifi ◽  
Maryam Salili ◽  
...  

2021 ◽  
Vol 22 (3) ◽  
pp. 1019
Author(s):  
Shira Engelberg ◽  
Yuexi Lin ◽  
Yehuda G. Assaraf ◽  
Yoav D. Livney

Selectively targeted drug delivery systems are preferable chemotherapeutic platforms, as they specifically deliver the drug cargo into tumor cells, while minimizing untoward toxic effects. However, these delivery systems suffer from insufficient encapsulation efficiency (EE), encapsulation capacity (EC), and premature drug release. Herein, we coencapsulated paclitaxel (PTX) and Jasmine oil (JO) within PEG-PCL nanoparticles (NPs), with an average diameter < 50 nm, selectively targeted to non-small cell lung cancer (NSCLC) cells, via S15-aptamer (APT) decoration. JO was selected as an “adhesive” oily core to enhance PTX entrapment, as JO and PTX share similar hydrophobicity and terpenoid structure. JO markedly enhanced EE of PTX from 23% to 87.8% and EC from 35 ± 6 to 74 ± 8 µg PTX/mg PEG-PCL. JO also markedly increased the residual amount of PTX after 69 h, from 18.3% to 65%. Moreover, PTX cytotoxicity against human NSCLC A549 cells was significantly enhanced due to the co-encapsulation with JO; the IC50 value for PTX encapsulated within JO-containing APT-NPs was 20-fold lower than that for APT-NPs lacking JO. Remarkably, JO-containing APT-NPs displayed a 6-fold more potent cell-killing, relatively to the free-drug. Collectively, these findings reveal a marked synergistic contribution of JO to the cytotoxic activity of APT-NP-based systems, for targeted PTX delivery against NSCLC, which may be readily applied to various hydrophobic chemotherapeutics.


2017 ◽  
Vol 74 ◽  
pp. 167-176 ◽  
Author(s):  
Poornima Agrawal ◽  
Rahul Pratap Singh ◽  
Sonali ◽  
Laksmi Kumari ◽  
Gunjan Sharma ◽  
...  

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Hoon Sim ◽  
Anne Neubauer ◽  
Shelton Caruthers ◽  
Gregory Lanza ◽  
Samuel Wickline ◽  
...  

Cardiovascular molecular imaging with targeted nanoparticles has emerged as a promising method for early detection of atherosclerosis and vulnerable plaque. However, traditional pharmacokinetic models for diffusible drugs are inadequate to describe the efficacy of nanoparticle carriers of diagnostic and therapeutic cargos. To quantify blood and MRI tissue signals from gadolinium-loaded nanoparticles (Gd-NP) targeted to avb3 integrins expressed on angiogenic capillaries in the aortas of cholesterol-fed rabbit, a novel 4 compartment open PK model was developed that utilized a unique simultaneous fitting scheme. In 10 rabbits fed 0.25% cholesterol for 3 months, the concentration of nanoparticles was measured serially from blood samples after injection of 1 ml/kg of targeted or nontargeted Gd-NP. The MRI proton signatures emanating from nanoparticles bound to the expanded vasa vasorum of the descending thoracic aorta was computed for all aortic cross sections in 1.5T T1w fa-suppressed spin-echo images. Based on the PK analysis, the concentration of targeted nanoparticles in the aortic wall is double that of non-targeted nanoparticles. Notably, this signal enhancement is achieved with 20x less gadolinium (4.6x10 −3 mmol Gd/kg BW) as compared with the dose of conventional gadolinium agents (0.1 mmol/kg). Further, the PK analysis shows that the targeted nanoparticles are more than three times more effective at reaching the aortic wall. These results should facilitate development and use of nanotechnologies intended for early detection of atherosclerosis and provide enhanced understanding of the kinetics and mechanisms of active targeting of plaque angiogenesis.


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