Nanoparticle-Cell Interactions: Drug Delivery Implications

Harush-Frenkel, Oshrat; Altschuler, Yoram; Benita, Simon

doi:10.1615/critrevtherdrugcarriersyst.v25.i6.10

Cited by 60 publications

(52 citation statements)

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“…Despite exposure to high docetaxel blood levels following oral administration, the rats showed no side effects; neither losing weight nor developing any visual lesions. We hypothesize that the NCs were internalized intact in the enterocytes through an endocytosis process (27), enhancing docetaxel absorption and preventing damage to mucosal tissue that could be elicited by high, free docetaxel molecule concentration. With these findings, the question of cytotoxicity of docetaxel on Walker 256 carcinoma cell line was addressed.…”

Section: Discussionmentioning

confidence: 99%

High Plasma Levels and Effective Lymphatic Uptake of Docetaxel in an Orally Available Nanotransporter Formulation

et al. 2011

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Docetaxel, an efficient chemotherapeutic drug, exhibits low and variable oral bioavailability due to the active efflux by P-glycoprotein (P-gp) and more so to CYP3A4 gut metabolism. Using a spray-drying technique, docetaxel was incorporated in PLGA [poly(lactic-co-glycolic acid)] nanocapsules (NC) which were embedded in entero-coated microparticles. An oral administration of the NC formulation elicited a higher absolute bioavailability than both a docetaxel solution (276%) and a free docetaxel NC formulation (400%) injected intravenously, a 5-mg/kg dose. The batches (B) I and II NC formulations elicited C max values that were 1,735% and 2,254%, respectively; higher than the C max value of the oral docetaxel solution combined with blank microparticles, a 10-mg/kg dose. No significant difference in AUC (area under curve) was observed between the batches. These unexpected results can be explained only if the pharmacokinetics of docetaxel had been modified. It was shown that NCs released from the microparticles penetrated the enterocytes, bypassing P-gp; apparently circumventing gut metabolism and accumulating within the lymphatic system from where both intact or biodegraded NCs and free docetaxel were progressively released into the circulation as plausibly supported by the fluorescent imaging results. Furthermore, the circulating docetaxel in plasma was unencapsulated and circulated either in free form or bound to albumin. Both free docetaxel NCs and microparticles exhibited in vitro efficacy on WRC 256 cells suggesting that the activity of docetaxel was not altered. This delivery concept has potential for clinical translation, perhaps allowing docetaxel chemotherapy to be switched from intravenous to oral delivery. Cancer Res; 71(8); 3018-28. Ó2011 AACR.

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Section: Discussionmentioning

confidence: 99%

High Plasma Levels and Effective Lymphatic Uptake of Docetaxel in an Orally Available Nanotransporter Formulation

et al. 2011

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“…The reduction in RP (%) caused by the 5-FU-loaded PBCA and PCL NPs could be the consequence of a faster (and more intense) 5-FU internalization by malignant cells, therefore facilitating greater drug concentrations within the cancer cells. Furthermore, NP internalization within cancer cells depends not only on their hydrophilic/hydrophobic character and physical chemistry (i.e., size and surface charge) but also on the endocytosis processes involved which can be considered to be more important in tumor cells (48,49).…”

Section: Discussionmentioning

confidence: 99%

Poly(butylcyanoacrylate) and Poly(ε-caprolactone) Nanoparticles Loaded with 5-Fluorouracil Increase the Cytotoxic Effect of the Drug in Experimental Colon Cancer

Ortíz

Cabeza

Arias

et al. 2015

AAPS J

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ABSTRACT. The clinical use of 5-fluorouracil, one of the drugs of choice in colon cancer therapy, is limited by a nonuniform oral absorption, a short plasma half-life, and by the development of drug resistances by malignant cells. We hypothesized that the formulation of biodegradable nanocarriers for the efficient delivery of this antitumor drug may improve its therapeutic effect against advanced or recurrent colon cancer. Hence, we have engineered two 5-fluorouracil-loaded nanoparticulate systems based on the biodegradable polymers poly(butylcyanoacrylate) and poly(ε-caprolactone). Drug incorporation to the nanosystems was accomplished by entrapment (encapsulation/dispersion) within the polymeric network during nanoparticle synthesis, i.e., by anionic polymerization of the monomer and interfacial polymer disposition, respectively. Main factors determining 5-fluorouracil incorporation within the polymeric nanomatrices were investigated. These nanocarriers were characterized by high drug entrapment efficiencies and sustained drug-release profiles. In vitro studies using human and murine colon cancer cell lines demonstrated that both types of nanocarriers significantly increased the antiproliferative effect of the encapsulated drug. In addition, both nanoformulations produced in vivo an intense tumor growth inhibition and increased the mice survival rate, being the greater tumor volume reduction obtained when using the poly(ε-caprolactone)-based formulation. These results suggest that these nanocarriers may improve the antitumor activity of 5-fluorouracil and could be used against advanced or recurrent colon cancer.

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“…The used uptake pathway and consequences of NP internalization are highly influenced by NP properties such as size, 27,28 shape, 27,29 and surface properties, 10,[30][31][32][33] as well as the physiology of the targeted cell type. 34,35 The behavior of the cell in terms of size, type, and frequency of endocytosis, division rate, and level of metabolism can result in toxic effects of seemingly biocompatible NPs as well as different intracellular fate of NPs, 34,[36][37][38][39][40] which is crucial for NP applications.…”

Section: Introductionmentioning

confidence: 99%

Cell type-specific response to high intracellular loading of polyacrylic acid-coated magnetic nanoparticles

Lojk¹,

Bregar²,

Rajh³

et al. 2015

IJN

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Magnetic nanoparticles (NPs) are a special type of NP with a ferromagnetic, electron-dense core that enables several applications such as cell tracking, hyperthermia, and magnetic separation, as well as multimodality. So far, superparamagnetic iron oxide NPs (SPIONs) are the only clinically approved type of metal oxide NPs, but cobalt ferrite NPs have properties suitable for biomedical applications as well. In this study, we analyzed the cellular responses to magnetic cobalt ferrite NPs coated with polyacrylic acid (PAA) in three cell types: Chinese Hamster Ovary (CHO), mouse melanoma (B16) cell line, and primary human myoblasts (MYO). We compared the internalization pathway, intracellular trafficking, and intracellular fate of our NPs using fluorescence and transmission electron microscopy (TEM) as well as quantified NP uptake and analyzed uptake dynamics. We determined cell viability after 24 or 96 hours’ exposure to increasing concentrations of NPs, and quantified the generation of reactive oxygen species (ROS) upon 24 and 48 hours’ exposure. Our NPs have been shown to readily enter and accumulate in cells in high quantities using the same two endocytic pathways; mostly by macropinocytosis and partially by clathrin-mediated endocytosis. The cell types differed in their uptake rate, the dynamics of intracellular trafficking, and the uptake capacity, as well as in their response to higher concentrations of internalized NPs. The observed differences in cell responses stress the importance of evaluation of NP–cell interactions on several different cell types for better prediction of possible toxic effects on different cell and tissue types in vivo.

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Nanoparticle-Cell Interactions: Drug Delivery Implications

Cited by 60 publications

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High Plasma Levels and Effective Lymphatic Uptake of Docetaxel in an Orally Available Nanotransporter Formulation

High Plasma Levels and Effective Lymphatic Uptake of Docetaxel in an Orally Available Nanotransporter Formulation

Poly(butylcyanoacrylate) and Poly(ε-caprolactone) Nanoparticles Loaded with 5-Fluorouracil Increase the Cytotoxic Effect of the Drug in Experimental Colon Cancer

Cell type-specific response to high intracellular loading of polyacrylic acid-coated magnetic nanoparticles

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Nanoparticle-Cell Interactions: Drug Delivery Implications

Cited by 60 publications

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High Plasma Levels and Effective Lymphatic Uptake of Docetaxel in an Orally Available Nanotransporter Formulation

High Plasma Levels and Effective Lymphatic Uptake of Docetaxel in an Orally Available Nanotransporter Formulation

Poly(butylcyanoacrylate) and Poly(ε-caprolactone) Nanoparticles Loaded with 5-Fluorouracil Increase the Cytotoxic Effect of the Drug in Experimental Colon Cancer

Cell type-specific response to high intracellular loading of polyacrylic acid-coated&nbsp;magnetic nanoparticles

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Cell type-specific response to high intracellular loading of polyacrylic acid-coated magnetic nanoparticles