scholarly journals Efficient entry of cell-penetrating peptide nona-arginine into adherent cells involves a transient increase in intracellular calcium

2015 ◽  
Vol 471 (2) ◽  
pp. 221-230 ◽  
Author(s):  
Kamran Melikov ◽  
Ann Hara ◽  
Kwabena Yamoah ◽  
Elena Zaitseva ◽  
Eugene Zaitsev ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Plasma Membrane ◽  
Intracellular Calcium ◽  
Temperature Drop ◽  
Cell Penetrating Peptide ◽  
Cationic Peptides ◽  
Adherent Cells ◽  
Drug Delivery Vehicles ◽  
Cell Penetrating ◽  
Delivery Vehicles

Mechanisms by which drug-delivery vehicles based on cationic peptides cross cell membranes remain unknown. We report that an increase in intracellular calcium triggered by temperature drop or high peptide concentrations transiently permeabilizes the plasma membrane for nona-arginine (R9) and delivers it to the cytosol.

scholarly journals Low concentration thresholds of plasma membranes for rapid energy-independent translocation of a cell-penetrating peptide

2009 ◽  
Vol 420 (2) ◽  
pp. 179-191 ◽  
Author(s):  
Catherine L. Watkins ◽  
Dirk Schmaljohann ◽  
Shiroh Futaki ◽  
Arwyn T. Jones
Keyword(s):  
Plasma Membrane ◽  
Cell Penetrating Peptides ◽  
Cell Penetrating Peptide ◽  
Cholesterol Depletion ◽  
Full Potential ◽  
Adherent Cells ◽  
High Porosity ◽  
Cellular Delivery ◽  
Suspension Cells ◽  
Cell Penetrating

The exact mechanisms by which cell-penetrating peptides such as oligo-arginines and penetratin cross biological membranes has yet to be elucidated, but this is required if they are to reach their full potential as cellular delivery vectors. In the present study, qualitative and quantitative analysis of the influence of temperature, peptide concentration and plasma membrane cholesterol on the uptake and subcellular distribution of the model cell-penetrating peptide octa-arginine was performed in a number of suspension and adherent cell lines. When experiments were performed on ice, the peptide at 2 μM extracellular concentration efficiently entered and uniformly labelled the cytoplasm of all the suspension cells studied, but a 10-fold higher concentration was required to observe similar results in adherent cells. At 37 °C and at higher peptide concentrations, time-lapse microscopy experiments showed that the peptide rapidly penetrated the entire plasma membrane of suspension cells, with no evidence of a requirement for nucleation zones to promote this effect. Cholesterol depletion with methyl-β-cyclodextrin enhanced translocation of octa-arginine across the plasma membrane of suspension cells at 37 °C, but decreased overall peptide accumulation. Under the same conditions in adherent cells this agent had no effect on peptide uptake or distribution. Cholesterol depletion increased the overall accumulation of the peptide at 4 °C in KG1a cells, but this effect could be reversed by re-addition of cholesterol as methyl-β-cyclodextrin–cholesterol complexes. The results highlight the relatively high porosity of the plasma membrane of suspension cells to this peptide, especially at low temperatures, suggesting that this feature could be exploited for delivering bioactive entities.

Dendrimers: General Aspects, Applications and Structural Exploitations as Prodrug/Drug-delivery Vehicles in Current Medicine

2018 ◽  
Vol 18 (5) ◽  
pp. 439-457 ◽  
Author(s):  
Merina Mariyam ◽  
Kajal Ghosal ◽  
Sabu Thomas ◽  
Nandakumar Kalarikkal ◽  
Mahima S. Latha
Keyword(s):  
Drug Delivery ◽  
Drug Delivery Vehicles ◽  
Delivery Vehicles ◽  
General Aspects

Novel Phospholipid-Based Labrasol Nanomicelles Loaded Flavonoids for Oral Delivery with Enhanced Penetration and Anti-Brain Tumor Efficiency

2020 ◽  
Vol 17 (3) ◽  
pp. 229-245
Author(s):  
Gang Wang ◽  
Junjie Wang ◽  
Rui Guan
Keyword(s):  
Drug Delivery ◽  
Brain Tumor ◽  
Oral Delivery ◽  
Safe Delivery ◽  
Drug Delivery Vehicles ◽  
Therapeutic Benefits ◽  
Delivery Vehicles ◽  
The Brain

Background: Owing to the rich anticancer properties of flavonoids, there is a need for their incorporation into drug delivery vehicles like nanomicelles for safe delivery of the drug into the brain tumor microenvironment. Objective: This study, therefore, aimed to prepare the phospholipid-based Labrasol/Pluronic F68 modified nano micelles loaded with flavonoids (Nano-flavonoids) for the delivery of the drug to the target brain tumor. Methods: Myricetin, quercetin and fisetin were selected as the initial drugs to evaluate the biodistribution and acute toxicity of the drug delivery vehicles in rats with implanted C6 glioma tumors after oral administration, while the uptake, retention, release in human intestinal Caco-2 cells and the effect on the brain endothelial barrier were investigated in Human Brain Microvascular Endothelial Cells (HBMECs). Results: The results demonstrated that nano-flavonoids loaded with myricetin showed more evenly distributed targeting tissues and enhanced anti-tumor efficiency in vivo without significant cytotoxicity to Caco-2 cells and alteration in the Trans Epithelial Electric Resistance (TEER). There was no pathological evidence of renal, hepatic or other organs dysfunction after the administration of nanoflavonoids, which showed no significant influence on cytotoxicity to Caco-2 cells. Conclusion: In conclusion, Labrasol/F68-NMs loaded with MYR and quercetin could enhance antiglioma effect in vitro and in vivo, which may be better tools for medical therapy, while the pharmacokinetics and pharmacodynamics of nano-flavonoids may ensure optimal therapeutic benefits.

scholarly journals Biodistribution and Pharmacokinectics of Liposomes and Exosomes in a Mouse Model of Sepsis

Pharmaceutics ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 427
Author(s):  
Amin Mirzaaghasi ◽  
Yunho Han ◽  
So-Hee Ahn ◽  
Chulhee Choi ◽  
Ji-Ho Park
Keyword(s):  
Drug Delivery ◽  
Therapeutic Potential ◽  
Hek293t Cell ◽  
Biological Properties ◽  
Context Analysis ◽  
Drug Delivery Vehicles ◽  
Delivery Vehicles ◽  
Diseased State ◽  
Sepsis And Septic Shock

Exosomes have attracted considerable attention as drug delivery vehicles because their biological properties can be utilized for selective delivery of therapeutic cargoes to disease sites. In this context, analysis of the in vivo behaviors of exosomes in a diseased state is required to maximize their therapeutic potential as drug delivery vehicles. In this study, we investigated biodistribution and pharmacokinetics of HEK293T cell-derived exosomes and PEGylated liposomes, their synthetic counterparts, into healthy and sepsis mice. We found that biodistribution and pharmacokinetics of exosomes were significantly affected by pathophysiological conditions of sepsis compared to those of liposomes. In the sepsis mice, a substantial number of exosomes were found in the lung after intravenous injection, and their prolonged blood residence was observed due to the liver dysfunction. However, liposomes did not show such sepsis-specific effects significantly. These results demonstrate that exosome-based therapeutics can be developed to manage sepsis and septic shock by virtue of their sepsis-specific in vivo behaviors.

scholarly journals Advances in Molecularly Imprinted Polymers as Drug Delivery Systems

Molecules ◽  
2021 ◽  
Vol 26 (12) ◽  
pp. 3589
Author(s):  
Rui Liu ◽  
Alessandro Poma
Keyword(s):  
Drug Delivery ◽  
Molecularly Imprinted Polymers ◽  
Drug Loading ◽  
Stimuli Responsive ◽  
Molecularly Imprinted ◽  
Imprinted Polymers ◽  
Drug Delivery Vehicles ◽  
The Past ◽  
Drug Molecules ◽  
Delivery Vehicles

Despite the tremendous efforts made in the past decades, severe side/toxic effects and poor bioavailability still represent the main challenges that hinder the clinical translation of drug molecules. This has turned the attention of investigators towards drug delivery vehicles that provide a localized and controlled drug delivery. Molecularly imprinted polymers (MIPs) as novel and versatile drug delivery vehicles have been widely studied in recent years due to the advantages of selective recognition, enhanced drug loading, sustained release, and robustness in harsh conditions. This review highlights the design and development of strategies undertaken for MIPs used as drug delivery vehicles involving different drug delivery mechanisms, such as rate-programmed, stimuli-responsive and active targeting, published during the course of the past five years.

scholarly journals A Review on Allopathic and Herbal Nanofibrous Drug Delivery Vehicles for Cancer Treatments

2021 ◽  
pp. e00663
Author(s):  
Tarun Mateti ◽  
Surabhi Aswath ◽  
Anoop Kishore Vatti ◽  
Agneya Kamath ◽  
Anindita Laha
Keyword(s):  
Drug Delivery ◽  
Cancer Treatments ◽  
Drug Delivery Vehicles ◽  
Delivery Vehicles

scholarly journals Exploring the utility of hybrid siloxane-phosphocholine (SiPC) liposomes as drug delivery vehicles

RSC Advances ◽  
2021 ◽  
Vol 11 (21) ◽  
pp. 13014-13023
Author(s):  
Mark B. Frampton ◽  
Andrea Blais ◽  
Zachary Raczywolski ◽  
Alan Castle ◽  
Paul M. Zelisko
Keyword(s):  
Drug Delivery ◽  
Aqueous Media ◽  
Unilamellar Vesicles ◽  
Drug Delivery Vehicles ◽  
Delivery Vehicles

Hybrid siloxane-phosphocholines (SiPCs) are a unique class of lipids that spontaneously form unilamellar vesicles (ULVs) that are ∼100 nm in diameter upon exposure to aqueous media without the need for extrusion and can be used as delivery vehicles.

scholarly journals Well-defined single polymer nanoparticles for the antibody-targeted delivery of chemotherapeutic agents

2015 ◽  
Vol 6 (8) ◽  
pp. 1286-1299 ◽  
Author(s):  
D. D. Lane ◽  
D. Y. Chiu ◽  
F. Y. Su ◽  
S. Srinivasan ◽  
H. B. Kern ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Targeted Drug Delivery ◽  
Targeted Delivery ◽  
Raft Polymerization ◽  
Chemotherapeutic Agents ◽  
Polymer Nanoparticles ◽  
Drug Delivery Vehicles ◽  
Molecular Weights ◽  
Delivery Vehicles ◽  
Targeted Drug

Second generation polymeric brushes with molecular weights in excess of 106 Da were synthesize via RAFT polymerization for use as antibody targeted drug delivery vehicles.

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