The Effect of Nanoparticle Size on Margination and Adhesion Propensity in Artificial Micro-Capillaries

2012 ◽  
Author(s):  
Patrick Jurney ◽  
Rachit Agarwal ◽  
Vikramjit Singh ◽  
Krishnendu Roy ◽  
S. V. Sreenivasan ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Rational Design ◽  
Flow Behavior ◽  
Cancer Therapeutics ◽  
Nanoparticle Size ◽  
Microfluidic Channels ◽  
Elliptical Cross ◽  
Drug Delivery Vehicles ◽  
Hemodynamic Forces

Intravenous injection of nanoparticles as drug delivery vehicles is a common practice used in in-vivo and clinical trials of therapeutic agents to target specific cancerous or pathogenic sites. The vascular flow dynamics of nanocarriers in human capillaries play an important role in the ultimate efficacy of this drug delivery method. This article reports an experimental study of the effect of nanoparticle size on their margination and adhesion propensity in micro fabricated microfluidic channels of a half elliptical cross-section. Spherical polystyrene particles ranging in diameter from 60 to 970 nm were flown in the microchannels and individual particles adhered to either the channel’s top or bottom wall were imaged using fluorescence microscopy. The results show a significant increase in adhesion for particles with diameter below 200 nm as well as the emergence of a critical nanoparticle diameter of about 970 nm, where no nanoparticle adherence was observed on the top wall. For the same particle number concentration, the total volume of the nanoparticles adhered to the top and bottom walls was found to increase with decreasing diameter for diameters less than 200 nm. The results are explained by the competition between Brownian motion, gravity and hemodynamic forces on the nanoparticles. These findings on the flow behavior of spherical nanoparticles in artificial micro-capillaries provide further insight for the rational design of nanocarriers for targeted cancer therapeutics.

Size-Dependent Nanoparticle Margination and Adhesion Propensity in a Microchannel

2013 ◽  
Vol 4 (3) ◽  
Author(s):  
Patrick Jurney ◽  
Rachit Agarwal ◽  
Vikramjit Singh ◽  
Krishnendu Roy ◽  
S. V. Sreenivasan ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Rational Design ◽  
Flow Behavior ◽  
Cancer Therapeutics ◽  
Bottom Wall ◽  
Microfluidic Channels ◽  
Elliptical Cross ◽  
Drug Delivery Vehicles ◽  
Shear Rates ◽  
Size Dependent

Intravenous injection of nanoparticles as drug delivery vehicles is a common practice in clinical trials of therapeutic agents to target specific cancerous or pathogenic sites. The vascular flow dynamics of nanocarriers (NCs) in human microcapillaries play an important role in the ultimate efficacy of this drug delivery method. This article reports an experimental study of the effect of nanoparticle size on their margination and adhesion propensity in microfluidic channels of a half-elliptical cross section. Spherical polystyrene particles ranging in diameter from 60 to 970 nm were flown in the microchannels and individual particles adhered to either the top or bottom wall of the channel were imaged using fluorescence microscopy. When the number concentration of particles in the flow was kept constant, the percentage of nanoparticles adhered to the top wall increased with decreasing diameter (d), with the number of particles adhered to the top wall following a d−3 trend. When the volume concentration of particles in solution was kept constant, no discernible trend was found. This experimental finding is explained by the competition between the Brownian force promoting margination and repulsive particle–particle electrostatic forces retarding adhesion to the wall. The 970 nm particles were found to adhere to the bottom wall much more than to the top wall for each of the three physiologically relevant shear rates tested, revealing the effect of gravitational force on the large particles. These findings on the flow behavior of spherical nanoparticles in artificial microcapillaries provide further insight for the rational design of NCs for targeted cancer therapeutics.

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 Physicochemical characterization, toxicity and in vivo biodistribution studies of a discoidal, lipid-based drug delivery vehicle: Lipodisq nanoparticles containing doxorubicin

2020 ◽  
Author(s):  
Maria Lyngaas Torgersen ◽  
Peter J. Judge ◽  
Juan F. Bada Juarez ◽  
Abhilash D. Pandya ◽  
Markus Fusser ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Physicochemical Characterization ◽  
Phospholipid Bilayer ◽  
Drug Delivery Vehicles ◽  
Carboxylate Groups ◽  
Biodistribution Studies ◽  
Aqueous Environments ◽  
Delivery Vehicles ◽  
Doxorubicin Release

AbstractMany promising pharmaceutically active compounds have low solubility in aqueous environments and their encapsulation into efficient drug delivery vehicles is crucial to increase their bioavailability. Lipodisq nanoparticles are approximately 10 nm in diameter and consist of a circular phospholipid bilayer, stabilized by an annulus of SMA (a hydrolysed copolymer of styrene and maleic anhydride). SMA is used extensively in structural biology to extract and stabilize integral membrane proteins for biophysical studies. Here, we assess the potential of these nanoparticles as drug delivery vehicles, determining their cytotoxicity and the in vivo excretion pathways of their polymer and lipid components. Doxorubicin-loaded Lipodisqs were cytotoxic across a panel of cancer cell lines, whereas nanoparticles without the drug had no effect on cell proliferation. Intracellular doxorubicin release from Lipodisqs in HeLa cells occurred in the low-pH environment of the endolysosomal system, consistent with the breakdown of the discoidal structure as the carboxylate groups of the SMA polymer become protonated. Biodistribution studies in mice showed that, unlike other nanoparticles injected intravenously, most of the Lipodisq components were recovered in the colon, consistent with rapid uptake by hepatocytes and excretion into bile. These data suggest that Lipodisqs have the potential to act as delivery vehicles for drugs and contrast agents.

scholarly journals Can nanotechnology potentiate photodynamic therapy?

2012 ◽  
Vol 1 (2) ◽  
pp. 111-146 ◽  
Author(s):  
Ying-Ying Huang ◽  
Sulbha K. Sharma ◽  
Tianhong Dai ◽  
Hoon Chung ◽  
Anastasia Yaroslavsky ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Photodynamic Therapy ◽  
Plasmonic Enhancement ◽  
Gold And Silver Nanoparticles ◽  
Drug Delivery Vehicles ◽  
Two Photon ◽  
Photon Excitation ◽  
Poorly Soluble ◽  
Delivery Vehicles

AbstractPhotodynamic therapy (PDT) uses the combination of nontoxic dyes and harmless visible light to produce reactive oxygen species that can kill cancer cells and infectious microorganisms. Due to the tendency of most photosensitizers (PS) to be poorly soluble and to form nonphotoactive aggregates, drug-delivery vehicles have become of high importance. The nanotechnology revolution has provided many examples of nanoscale drug-delivery platforms that have been applied to PDT. These include liposomes, lipoplexes, nanoemulsions, micelles, polymer nanoparticles (degradable and nondegradable), and silica nanoparticles. In some cases (fullerenes and quantum dots), the actual nanoparticle itself is the PS. Targeting ligands such as antibodies and peptides can be used to increase specificity. Gold and silver nanoparticles can provide plasmonic enhancement of PDT. Two-photon excitation or optical upconversion can be used instead of one-photon excitation to increase tissue penetration at longer wavelengths. Finally, after sections on in vivo studies and nanotoxicology, we attempt to answer the title question, “can nanotechnology potentiate PDT?”

scholarly journals An in vitro and in vivo bio-interaction responses and biosafety evaluation of novel Au–ZnTe core–shell nanoparticles

2016 ◽  
Vol 5 (4) ◽  
pp. 1078-1089 ◽  
Author(s):  
R. Dunpall ◽  
N. Revaprasadu
Keyword(s):  
Drug Delivery ◽  
Cancer Therapeutics ◽  
Surface Modifications ◽  
Core Shell ◽  
Support Surface ◽  
Shell Nanoparticles ◽  
Core Shell Nanoparticles ◽  
Biosafety Evaluation

Novel gold–zinc telluride (Au–ZnTe) core–shell nanoparticles were synthesized to support surface modifications for enhanced drug delivery in cancer therapeutics.

Cellular Internalization Mechanisms of Polyanhydride Particles: Implications for Rational Design of Drug Delivery Vehicles

2016 ◽  
Vol 12 (7) ◽  
pp. 1544-1552 ◽  
Author(s):  
Yashdeep Phanse ◽  
Paul Lueth ◽  
Amanda E. Ramer-Tait ◽  
Brenda R. Carrillo-Conde ◽  
Michael J. Wannemuehler ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Rational Design ◽  
Cellular Internalization ◽  
Drug Delivery Vehicles ◽  
Delivery Vehicles

scholarly journals Exosomes for mRNA delivery: a novel biotherapeutic strategy with hurdles and hope

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Cynthia Aslan ◽  
Seyed Hossein Kiaie ◽  
Naime Majidi Zolbanin ◽  
Parisa Lotfinejad ◽  
Reihaneh Ramezani ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Protein Expression ◽  
Messenger Rnas ◽  
Drug Delivery Vehicles ◽  
New Class ◽  
The Past ◽  
Recent Developments ◽  
Cell Sources ◽  
Delivery Vehicles

AbstractOver the past decade, therapeutic messenger RNAs (mRNAs) have emerged as a highly promising new class of drugs for protein replacement therapies. Due to the recent developments, the incorporation of modified nucleotides in synthetic mRNAs can lead to maximizing protein expression and reducing adverse immunogenicity. Despite these stunning improvements, mRNA therapy is limited by the need for the development of safe and efficient carriers to protect the mRNA integrity for in vivo applications. Recently, leading candidates for in vivo drug delivery vehicles are cell-derived exosomes, which have fewer immunogenic responses. In the current study, the key hurdles facing mRNA-based therapeutics, with an emphasis on recent strategies to overcoming its immunogenicity and instability, were highlighted. Then the immunogenicity and toxicity of exosomes derived from various cell sources were mentioned in detail. Finally, an overview of the recent strategies in using exosomes for mRNA delivery in the treatment of multiple diseases was stated.

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