Stearylated cycloarginine nanosystems for intracellular delivery – simulations, formulation and proof of concept

RSC Advances ◽  
2016 ◽  
Vol 6 (114) ◽  
pp. 113538-113550 ◽  
Author(s):  
V. Dhawan ◽  
A. Magarkar ◽  
G. Joshi ◽  
D. Makhija ◽  
A. Jain ◽  
...  
Keyword(s):  
Cellular Uptake ◽  
In Silico ◽  
Intracellular Delivery ◽  
Proof Of Concept ◽  
Reduced Toxicity

Novel cationic agent liposomes performed better in silico translating in higher cellular uptake with reduced toxicity.

Probing Cellular Outcomes Using Heterobivalent Constructs

2019 ◽  
Author(s):  
Rohit Bhadoria ◽  
Kefeng Ping ◽  
Christer Lohk ◽  
Ivar Järving ◽  
Pavel Starkov
Keyword(s):  
Cell Viability ◽  
Small Molecules ◽  
Cellular Uptake ◽  
Kinase Inhibitors ◽  
Rho Kinase ◽  
Intracellular Delivery ◽  
Rho Kinase Inhibitors

<div> <div> <div> <p>Conjugation techniques are central to improving intracellular delivery of bioactive small molecules. However, tracking and assessing the overall biological outcome of these constructs remains poorly understood. We addressed this issue by having developed a focused library of heterobivalent constructs based on Rho kinase inhibitors to probe various scenarios. By comparing induction of a phenotype of interest vs. cell viability vs. cellular uptake, we demonstrate that such conjugates indeed lead to divergent cellular outcomes. </p> </div> </div> </div>

Lead Molecule Prediction and Characterization for Designing MERS-CoV 3C-like Protease Inhibitors: An In silico Approach

2018 ◽  
Vol 15 (1) ◽  
pp. 82-88 ◽  
Author(s):  
Md. Mostafijur Rahman ◽  
Md. Bayejid Hosen ◽  
M. Zakir Hossain Howlader ◽  
Yearul Kabir
Keyword(s):  
Binding Energy ◽  
Middle East ◽  
Virtual Screening ◽  
In Silico ◽  
Screening Method ◽  
Middle East Respiratory Syndrome ◽  
Cytochrome P450 Enzymes ◽  
Drug Molecules ◽  
Essential Enzyme ◽  
Reduced Toxicity

Background: 3C-like protease also called the main protease is an essential enzyme for the completion of the life cycle of Middle East Respiratory Syndrome Coronavirus. In our study we predicted compounds which are capable of inhibiting 3C-like protease, and thus inhibit the lifecycle of Middle East Respiratory Syndrome Coronavirus using in silico methods. </P><P> Methods: Lead like compounds and drug molecules which are capable of inhibiting 3C-like protease was identified by structure-based virtual screening and ligand-based virtual screening method. Further, the compounds were validated through absorption, distribution, metabolism and excretion filtering. Results: Based on binding energy, ADME properties, and toxicology analysis, we finally selected 3 compounds from structure-based virtual screening (ZINC ID: 75121653, 41131653, and 67266079) having binding energy -7.12, -7.1 and -7.08 Kcal/mol, respectively and 5 compounds from ligandbased virtual screening (ZINC ID: 05576502, 47654332, 04829153, 86434515 and 25626324) having binding energy -49.8, -54.9, -65.6, -61.1 and -66.7 Kcal/mol respectively. All these compounds have good ADME profile and reduced toxicity. Among eight compounds, one is soluble in water and remaining 7 compounds are highly soluble in water. All compounds have bioavailability 0.55 on the scale of 0 to 1. Among the 5 compounds from structure-based virtual screening, 2 compounds showed leadlikeness. All the compounds showed no inhibition of cytochrome P450 enzymes, no blood-brain barrier permeability and no toxic structure in medicinal chemistry profile. All the compounds are not a substrate of P-glycoprotein. Our predicted compounds may be capable of inhibiting 3C-like protease but need some further validation in wet lab.

Efficient cellular uptake of click nucleic acid modified proteins

2020 ◽  
Vol 56 (35) ◽  
pp. 4820-4823 ◽  
Author(s):  
Albert Harguindey ◽  
Heidi R. Culver ◽  
Jasmine Sinha ◽  
Christopher N. Bowman ◽  
Jennifer N. Cha
Keyword(s):  
Nucleic Acid ◽  
Cellular Uptake ◽  
Intracellular Delivery ◽  
Modified Proteins

Efficient intracellular delivery of biomacromolecules such as proteins continues to remain a challenge despite its potential for medicine.

Synthesis, Cellular Uptake, and Cytotoxicity of a Thermally Responsive Nanocapsule

2009 ◽  
Author(s):  
Wujie Zhang ◽  
Jianhua Rong ◽  
Qian Wang ◽  
Xiaoming He
Keyword(s):  
Cellular Uptake ◽  
Blood Cells ◽  
Mammalian Cells ◽  
Polymeric Nanoparticles ◽  
Intracellular Delivery ◽  
Sustained Delivery ◽  
Hydrogel Nanoparticles ◽  
Ambient Temperatures ◽  
Thermally Responsive ◽  
Therapeutic Drugs

Recently, polymeric nanoparticles have attracted tremendous interests as a useful tool to encapsulate therapeutic drugs, genes, and proteins for their controlled and sustained delivery. Among them, polymeric hydrogel nanoparticles with thermal and/or pH responsiveness have attracted particular attention [1]. Trehalose, a non-reducing disaccharide of glucose, has been demonstrated to be a potent, nontoxic bioprotectant for stabilizing lipids, proteins, viruses, and blood cells at cryogenic and particularly, ambient temperatures (i.e., cryo and lyopreservation) [2]. However, intracellular delivery of trehalose into small eukaryotic mammalian cells in a large quantity for biostabilization purpose has not been very successful so far [2]. In this study, a thermally responsive polymeric nanocapsule was synthesized and characterized with the aim to encapsulate trehalose for its intracellular delivery.

scholarly journals Peptides modulating conformational changes in secreted chaperones: From in silico design to preclinical proof of concept

2009 ◽  
Vol 106 (33) ◽  
pp. 13797-13801 ◽  
Author(s):  
Y. Kliger ◽  
O. Levy ◽  
A. Oren ◽  
H. Ashkenazy ◽  
Z. Tiran ◽  
...  
Keyword(s):  
Conformational Changes ◽  
In Silico ◽  
Proof Of Concept ◽  
In Silico Design

Co-encapsulation of gemcitabine and tocotrienols in nanovesicles enhanced efficacy in pancreatic cancer

Nanomedicine ◽  
2021 ◽  
Vol 16 (5) ◽  
pp. 373-389
Author(s):  
Geetha Maniam ◽  
Chun-Wai Mai ◽  
Mohd Zulkefeli ◽  
Ju-Yen Fu
Keyword(s):  
Pancreatic Cancer ◽  
Polyethylene Glycol ◽  
Cancer Cells ◽  
Cellular Uptake ◽  
Proof Of Concept ◽  
Pancreatic Cancer Cells ◽  
Polyethylene Glycol 1000 ◽  
Span 60 ◽  
Dual Drug

Aim: To synthesize niosomes co-encapsulating gemcitabine (GEM) and tocotrienols, and physicochemically characterize and evaluate the antipancreatic effects of the nanoformulation on Panc 10.05, SW 1990, AsPC-1 and BxPC-3 cells. Materials & methods: Niosomes-entrapping GEM and tocotrienols composed of Span 60, cholesterol and D-α-tocopheryl polyethylene glycol 1000 succinate were produced by Handjani-Vila and film hydration methods. Results: The film hydration produced vesicles measuring 161.9 ± 0.5 nm, approximately 50% smaller in size than Handjani-Vila method, with maximum entrapment efficiencies of 20.07 ± 0.22% for GEM and 34.52 ± 0.10% for tocotrienols. In Panc 10.05 cells, GEM’s antiproliferative effect was enhanced 2.78-fold in combination with tocotrienols. Niosomes produced a significant ninefold enhancement in cytotoxicity of the combination, supported by significantly higher cellular uptake of GEM in the cells. Conclusion: This study is a proof of concept on the synthesis of dual-drug niosomes and their efficacy on pancreatic cancer cells in vitro.

Intracellular Delivery of Etoposide Loaded Biodegradable Nanoparticles: Cytotoxicity and Cellular Uptake Studies

2011 ◽  
Vol 11 (8) ◽  
pp. 6657-6667 ◽  
Author(s):  
Khushwant S. Yadav ◽  
Sheeba Jacob ◽  
Geetanjali Sachdeva ◽  
Krutika K. Sawant
Keyword(s):  
Cellular Uptake ◽  
Intracellular Delivery ◽  
Biodegradable Nanoparticles ◽  
Uptake Studies
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