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.

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.

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 Rational design of multistage drug delivery vehicles for pulmonary RNA interference therapy

2020 ◽  
Vol 591 ◽  
pp. 119989
Author(s):  
A. Sofia Silva ◽  
Kevin E. Shopsowitz ◽  
Santiago Correa ◽  
Stephen W. Morton ◽  
Erik C. Dreaden ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Rna Interference ◽  
Rational Design ◽  
Drug Delivery Vehicles ◽  
Delivery Vehicles

scholarly journals Exosomes: Cell-Derived Nanoplatforms for the Delivery of Cancer Therapeutics

2020 ◽  
Vol 22 (1) ◽  
pp. 14
Author(s):  
Hyosuk Kim ◽  
Eun Hye Kim ◽  
Gijung Kwak ◽  
Sung-Gil Chi ◽  
Sun Hwa Kim ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Therapeutic Potential ◽  
Cancer Therapeutics ◽  
Strong Stability ◽  
Target Cells ◽  
Drug Delivery Vehicles ◽  
Exosome Biogenesis ◽  
Donor Cells ◽  
Delivery Vehicles ◽  
Targeting Ability

Exosomes are cell-secreted nanovesicles that naturally contain biomolecular cargoes such as lipids, proteins, and nucleic acids. Exosomes mediate intercellular communication, enabling the transfer biological signals from the donor cells to the recipient cells. Recently, exosomes are emerging as promising drug delivery vehicles due to their strong stability in blood circulation, high biocompatibility, low immunogenicity, and natural targeting ability. In particular, exosomes derived from specific types of cells can carry endogenous signaling molecules with therapeutic potential for cancer treatment, thus presenting a significant impact on targeted drug delivery and therapy. Furthermore, exosomes can be engineered to display targeting moieties on their surface or to load additional therapeutic agents. Therefore, a comprehensive understanding of exosome biogenesis and the development of efficient exosome engineering techniques will provide new avenues to establish convincing clinical therapeutic strategies based on exosomes. This review focuses on the therapeutic applications of exosomes derived from various cells and the exosome engineering technologies that enable the accurate delivery of various types of cargoes to target cells for cancer therapy.

scholarly journals The Combination of Morphology and Surface Chemistry Defines the Biological Identity of Nanocarriers in Human Blood

2020 ◽  
Author(s):  
Nicholas B. Karabin ◽  
Michael P. Vincent ◽  
Sean D. Allen ◽  
Sharan Bobbala ◽  
Molly A. Frey ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Surface Chemistry ◽  
Human Blood ◽  
Rational Design ◽  
Immune Cell ◽  
Protein Corona ◽  
Blood Proteins ◽  
Drug Delivery Vehicles ◽  
Corona Formation ◽  
Delivery Vehicles

AbstractFollowing intravenous administration, an adsorbed corona of blood proteins immediately forms on the surfaces of nanocarriers to confer a distinct biological identity that dictates interactions with the immune system. While the nanocarrier surface chemistry has long been the focus of protein corona formation, the influence of the nanocarrier structure has remained unclear despite well-documented influences on biodistribution, clearance and inflammation. Here, we present design rules for the combined engineering of both nanocarrier structure and surface chemistry derived from a comprehensive proteomic analysis of protein corona formation in human blood. A library of nine soft PEGylated nanocarriers that differ in their combination of morphology (spheres, vesicles, and cylinders) and surface chemistry (methoxy, hydroxyl, and phosphate) were synthesized to represent properties of commonly employed drug delivery vehicles. Using label-free proteomics and high-throughput techniques, we examined the relationship between physicochemical properties and the resulting nanocarrier biological identity, including dynamic changes in protein corona composition, differential immunostimulation and uptake by relevant immune cell populations. In human blood, non-polar spherical micelles developed a similar biological identity to polar vesicles, whereas the identities of polar spheres and cylinders resembled that of non-polar vesicles. The formed protein coronas were compositionally dynamic and morphology-dependent, and these time-dependent fingerprints altered nanocarrier complement activation as well as their uptake by human monocytes, macrophages, and dendritic cells. This comprehensive analysis provides mechanistic insights into rational design choices that impact nanocarrier fate in human blood.One Sentence SummaryWe demonstrate that not only the surface chemistry, but the combined chemical and structural properties of soft drug delivery vehicles impact the composition of blood proteins that adsorb to their surfaces, and these differences specify their interactions with and modulation of human immune cells.

Advances in the use of MOFs for Cancer Diagnosis and Treatment: An Overview

2020 ◽  
Vol 26 (33) ◽  
pp. 4174-4184
Author(s):  
Marina P. Abuçafy ◽  
Bruna L. da Silva ◽  
João A. Oshiro-Junior ◽  
Eloisa B. Manaia ◽  
Bruna G. Chiari-Andréo ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Drug Delivery Systems ◽  
Rational Design ◽  
Gas Adsorption ◽  
Drug Loading ◽  
Drug Carriers ◽  
Delivery Systems ◽  
Academic Community ◽  
Anticancer Drug Delivery ◽  
Diagnostic Agents

Nanoparticles as drug delivery systems and diagnostic agents have gained much attention in recent years, especially for cancer treatment. Nanocarriers improve the therapeutic efficiency and bioavailability of antitumor drugs, besides providing preferential accumulation at the target site. Among different types of nanocarriers for drug delivery assays, metal-organic frameworks (MOFs) have attracted increasing interest in the academic community. MOFs are an emerging class of coordination polymers constructed of metal nodes or clusters and organic linkers that show the capacity to combine a porous structure with high drug loading through distinct kinds of interactions, overcoming the limitations of traditional drug carriers explored up to date. Despite the rational design and synthesis of MOFs, structural aspects and some applications of these materials like gas adsorption have already been comprehensively described in recent years; it is time to demonstrate their potential applications in biomedicine. In this context, MOFs can be used as drug delivery systems and theranostic platforms due to their ability to release drugs and accommodate imaging agents. This review describes the intrinsic characteristics of nanocarriers used in cancer therapy and highlights the latest advances in MOFs as anticancer drug delivery systems and diagnostic agents.

Nano Drug Delivery in Treatment of Oral Cancer, A Review of the Literature

2019 ◽  
Vol 20 (10) ◽  
pp. 1008-1017 ◽  
Author(s):  
Vandita Kakkar ◽  
Manoj Kumar Verma ◽  
Komal Saini ◽  
Indu Pal Kaur
Keyword(s):  
Drug Delivery ◽  
Oral Cancer ◽  
Treatment Options ◽  
Oral Submucous Fibrosis ◽  
Survival Rates ◽  
Cancer Therapeutics ◽  
Developed Countries ◽  
Current Treatment ◽  
Poor Overall Survival ◽  
Hereditary Disorders

Oral Cancer (OC) is a serious and growing problem which constitutes a huge burden on people in more and less economically developed countries alike. The scenario is clearly depicted from the increase in the expected number of new cases in the US diagnosed with OC from 49,670 people in 2016, to 49,750 cases in 2017. The situation is even more alarming in India, with 75,000 to 80,000 new cases being reported every year, thus making it the OC capital of the world. Leukoplakia, erythroplakia, oral lichen planus, oral submucous fibrosis, discoid lupus erythmatosus, hereditary disorders such as dyskeratosis congenital and epidermolisys bullosa are highlighted by WHO expert working group as the predisposing factors increasing the risk of OC. Consumption of tobacco and alcohol, genetic factors, and human papilloma virus are assigned as the factors contributing to the aetiology of OC. On the other hand, pathogenesis of OC involves not only apoptosis but also pain, inflammation and oxidative stress. Inspite of current treatment options (surgery, radiotherapy, and chemotherapy), OC is often associated with recurrence and formation of secondary primary tumours resulting in poor overall survival rates (∼50%). The intervention of nano technology-based drug delivery systems as therapeutics for cancers is often viewed as a cutting edge for technologists. Though ample literature on the usefulness of nano-coutured cancer therapeutics, rarely any product is in pipeline. Yet, despite all the hype about nanotechnology, there are few ongoing trials. This review discusses the current and future trends of nano-based drug delivery for the treatment of OC.

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.

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