Drug Carrier Interaction With blood: a Critical Aspect for High-Efficient Vascular-Targeted Drug Delivery Systems

Sobczynski, Daniel J.; Fish, Margaret; Fromen, Catherine A.; Carasco-Teja, Mariana; Coleman, Rhima M.; Eniola‐Adefeso, Omolola

doi:10.4155/tde.15.38

Cited by 13 publications

(13 citation statements)

References 152 publications

(161 reference statements)

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“…Drug carrier interaction with serum proteins, which results in a carrier-protein corona, is a predictor for in vivo stability and applicability [ 20 , 21 , 22 , 23 ]. This behavior is common in the case of intravenous and oral administration of nanotherapeutics.…”

Section: Introductionmentioning

confidence: 99%

Tannic Acid-Lung Fluid Assemblies Promote Interaction and Delivery of Drugs to Lung Cancer Cells

et al. 2018

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Lung cancer (LC) is one of the leading causes of death in both men and women in the United States. Tannic acid (TA), a water-soluble polyphenol, exhibits a wide range of biological activities. TA has received much attention as a promising compound in the biomaterial and drug delivery fields. Lung fluid (LF) is a major barrier for distribution of drugs to the lungs. Therefore, the purpose of this study was to examine TA interaction with LF for effective delivery of anti-cancer drug molecules via pulmonary delivery. The extent of adsorption of LF proteins by TA was revealed by fluorescence quenching in fluorescence spectroscopy. The presence of LF in TA-LF complexes was noticed by the presence of protein peaks at 1653 cm−1. Both protein dot and SDS-PAGE analysis confirmed LF protein complexation at all TA concentrations employed. A stable particle TA-LF complex formation was observed through transmission electron microscopy (TEM) analysis. The complexation pattern measured by dynamic light scattering (DLS) indicated that it varies depending on the pH of the solutions. The degree of LF presence in TA-LF complexes signifies its interactive behavior in LC cell lines. Such superior interaction offered an enhanced anti-cancer activity of drugs encapsulated in TA-LF complex nanoformulations. Our results indicate that TA binds to LF and forms self-assemblies, which profoundly enhance interaction with LC cells. This study demonstrated that TA is a novel carrier for pharmaceutical drugs such as gemcitabine, carboplatin, and irinotecan.

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Section: Introductionmentioning

confidence: 99%

Tannic Acid-Lung Fluid Assemblies Promote Interaction and Delivery of Drugs to Lung Cancer Cells

et al. 2018

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“…These contrasts are likely due to variance in methodological approaches and encourages further investigations. Clinically, Tamoxifen is administered orally or intravenously (IV), depending on the severity, staging and patient preference; allowing for availability within the circulation as well as ultimate accumulation of the therapy at the tumour site 5,34 . In order to mimic these scenarios, in this study we present two co-culture models making use of blood constituents (whole blood, platelet-rich plasma and platelet-poor plasma) and breast cancer cell lines (MCF-7 and T47D): in Model 1, breast cancer cell lines were treated with a physiological dose of Tamoxifen prior to exposure to untreated blood constituents; whereas in Model 2, blood was treated with Tamoxifen prior to exposure to untreated breast cancer cell lines.…”

mentioning

confidence: 99%

Tamoxifen induces hypercoagulation and alterations in ERα and ERβ dependent on breast cancer sub-phenotype ex vivo

Pather

Augustine

2020

Sci Rep

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Tamoxifen shows efficacy in reducing breast cancer-related mortality but clinically, is associated with increased risk for thromboembolic events. We aimed to determine whether breast tumour sub-phenotype could predict propensity for thrombosis. We present two ex vivo Models of Tamoxifen-therapy, Model 1 in which treatment recapitulates accumulation within breast tissue, by treating MCF7 and T47D cells directly prior to exposure to blood constituents; and Model 2 in which we recreate circulating Tamoxifen by treating blood constituents prior to exposure to cancer cells. Blood constituents included whole blood, platelet-rich plasma and platelet-poor plasma. Hypercoagulation was assessed as a function of thrombin activity, expression of CD62P and CD63 activation markers defined as an index of platelet activation, and platelet morphology; while oestrogen receptor expression was assessed using immunocytochemistry with quantitative analysis. We determined, in concert with clinical studies and contrary to selected laboratory investigations, that Tamoxifen induces hypercoagulation, dependent on sub-phenotypes, with the T47D cell line capacity most enhanced. We determined a weak positive correlation between oestrogen receptor expression, and CD62P and CD63; indicating an association between tumour invasion profiles and hypercoagulation, however, other yet unknown factors may play a predictive role in defining hypercoagulation.

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“…It is important to note that the carboxylic acid and avidin surface density will be present as a distribution on the particle surface, which may cause particle-to-particle variation in the corona composition or conformation of adsorbed corona proteins [41,44,45]. To mitigate any potential contribution of batch-to-batch variations linked to the associated particle processing steps, VTC adhesion assays were performed head-to-head for each material type in the different suspending fluids, i.e.…”

Section: Discussionmentioning

confidence: 99%

Effect of anticoagulants on the protein corona-induced reduced drug carrier adhesion efficiency in human blood flow

Sobczynski

Eniola‐Adefeso

2017

Acta Biomaterialia

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Plasma proteins rapidly coat the surfaces of particulate drug carriers to form a protein corona upon their injection into the bloodstream. The high presence of immunoglobulins in the corona formed on poly(lactic-co-glycolic acid) (PLGA) vascular-targeted carrier (VTC) surfaces was recently shown to negatively impact their adhesion to activated endothelial cells (aECs) in vitro. Here, we characterized the influence of anticoagulants, or their absence, on the binding efficiency of VTCs of various materials via modulation of their protein corona. Specifically, we evaluated the adhesion of PLGA, poly(lactic acid) (PLA), polycaprolactone (PCL), silica, and polystyrene VTCs to aECs in heparinized, citrated, and non-anticoagulated (serum and whole) blood flows relative to buffer control. Particle adhesion is substantially reduced in non-anticoagulated blood flows regardless of the material type while only moderate to minimal reduction is observed for VTCs in anticoagulant-containing blood flow depending on the anticoagulant and material type. The substantial reduction in VTC adhesion in blood flows was linked to a high presence of immunoglobulin-sized proteins in the VTC corona via SDS-PAGE analysis. Of all the materials evaluated, PLGA was the most sensitive to plasma protein effects while PCL was the most resistant, suggesting particle hydrophobicity is a critical component of the observed negative plasma protein effects. Overall, this work demonstrates that anticoagulant positively alters the effect of plasma proteins in prescribing VTC adhesion to aECs in human blood flow, which has implication in the use of in vitro blood flow assays for functional evaluation of VTCs for in vivo use.

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Drug Carrier Interaction With blood: a Critical Aspect for High-Efficient Vascular-Targeted Drug Delivery Systems

Cited by 13 publications

References 152 publications

Tannic Acid-Lung Fluid Assemblies Promote Interaction and Delivery of Drugs to Lung Cancer Cells

Tannic Acid-Lung Fluid Assemblies Promote Interaction and Delivery of Drugs to Lung Cancer Cells

Tamoxifen induces hypercoagulation and alterations in ERα and ERβ dependent on breast cancer sub-phenotype ex vivo

Effect of anticoagulants on the protein corona-induced reduced drug carrier adhesion efficiency in human blood flow

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