Characterization of nanoparticle uptake by endothelial cells

Davda, Jasmine; Labhasetwar, Vinod

doi:10.1016/s0378-5173(01)00923-1

Cited by 476 publications

(316 citation statements)

References 29 publications

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“…122 An in vitro plasmid gene sustained release over several weeks was achieved with PLGA 123 or mPEG-PLA nanoparticles. 120 PLGA nanoparticles were shown to be endocytosed by cells in vitro 124 . After endocytosis, PLGA nanoparticles escape from the endolysosomal compartment to the cytoplasm and gradually release their content, resulting in sustained gene expression.…”

Section: Drug Loadingmentioning

confidence: 99%

Drug transport to brain with targeted nanoparticles

2005

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Summary: Nanoparticle drug carriers consist of solid biodegradable particles in size ranging from 10 to 1000 nm (50 -300 nm generally). They cannot freely diffuse through the bloodbrain barrier (BBB) and require receptor-mediated transport through brain capillary endothelium to deliver their content into the brain parenchyma. Polysorbate 80-coated polybutylcyanoacrylate nanoparticles can deliver drugs to the brain by a still debated mechanism. Despite interesting results these nanoparticles have limitations, discussed in this review, that may preclude, or at least limit, their potential clinical applications. Long-circulating nanoparticles made of methoxypoly(ethylene glycol)-polylactide or poly(lactide-co-glycolide) (mPEG-PLA/ PLGA) have a good safety profiles and provide drug-sustained release. The availability of functionalized PEG-PLA permits to prepare target-specific nanoparticles by conjugation of cell surface ligand. Using peptidomimetic antibodies to BBB transcytosis receptor, brain-targeted pegylated immunonanoparticles can now be synthesized that should make possible the delivery of entrapped actives into the brain parenchyma without inducing BBB permeability alteration. This review presents their general properties (structure, loading capacity, pharmacokinetics) and currently available methods for immunonanoparticle preparation.

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Section: Drug Loadingmentioning

confidence: 99%

Drug transport to brain with targeted nanoparticles

2005

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“…Targeted drug delivery to the endothelium may help to improve treatment of diseases affecting the vasculature [1][2][3][4][5][6][7]. Targeted drug delivery systems (DDSs) designed to achieve this goal consist of affinity vectors (e.g., antibodies directed to endothelial surface determinants) coupled either directly to pharmacological cargoes (e.g., therapeutic enzymes) or to drugloaded vehicles or carriers (e.g., liposomes or polymer nanocarriers) [8][9][10][11][12][13][14].…”

Section: Introductionmentioning

confidence: 99%

Factors modulating the delivery and effect of enzymatic cargo conjugated with antibodies targeted to the pulmonary endothelium

Shuvaev

Christofidou‐Solomidou

Scherpereel

et al. 2007

Journal of Controlled Release

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Vascular drug targeting may improve therapies, yet a thorough understanding of the factors that regulate effects of drugs directed to the endothelium is needed to translate this approach into the clinical domain. To define factors modulating the efficacy and effects of endothelial targeting, we used a model enzyme (glucose oxidase, GOX) coupled with monoclonal antibodies (anti-TM 34 or anti-TM 201 ) to distinct epitopes of thrombomodulin, a surface determinant enriched in the pulmonary endothelium. GOX delivery results in conversion of glucose and oxygen into H 2 O 2 leading to lung damage, a clear physiologic endpoint. Results of in vivo studies in mice showed that the efficiency of cargo delivery and its effect are influenced by a number of factors including: 1) The level of pulmonary uptake of the targeting antibody (anti-TM 201 was more efficient than anti-TM 34 ); 2) The amount of an active drug delivered to the target; 3) The amount of target antigen on the endothelium (animals with suppressed TM levels showed less targeting); and, 4) The substrate availability for the enzyme cargo in the target tissue (hyperoxia augmented GOX-induced injury). Therefore, both activity of the conjugates and biological factors control targeting and effects of enzymatic cargo. Understanding the nature of such "modulating biological factors" will hopefully allow optimization and ultimately applications of drug targeting for "individualized" pharmacotherapy.

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“…The generation of smaller wear debris particles that include nanoparticles [19,34,38,39,61] suggests that the reduction in osteolytic potential resulting from highly crosslinked UHMWPE could prove to be lower than predicted by the improvement in wear rates. Although interactions with fine and ultrafine particles are mainly confined to phagocytic cells, certain nanoparticles have been shown to accumulate in the cytoplasm of endothelial cells [15], fibroblasts [31,44], and an epithelial cell line (HeLa cells) [79]. It is now also apparent that nanoparticles may impact the nucleus of the cell [14,57], and although no overt cytotoxic events resulting from highly crosslinked UHMWPE debris have been reported, we should remain cautious that nanoparticle exposure might result in an unusual effect on cell function and regulation.…”

Section: Search Strategy and Criteriamentioning

confidence: 99%

How Has the Introduction of New Bearing Surfaces Altered the Biological Reactions to Byproducts of Wear and Modularity?

Wooley

2014

Clin Orthop Relat Res

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Background Biological responses to wear debris were largely elucidated in studies focused on conventional ultrahigh-molecular-weight polyethylene (UHMWPE) and some investigations of polymethymethacrylate cement and orthopaedic metals. However, newer bearing couples, in particular metal-on-metal but also ceramic-on-ceramic bearings, may induce different biological reactions. Questions/purposes Does wear debris from the newer bearing surfaces result in different biological responses compared with the known responses observed with conventional metal-on-UHMWPE bearings?Methods A Medline search of articles published after 1996 supplemented by a hand search of reference lists of included studies and relevant conference proceedings was conducted to identify the biological responses to orthopaedic wear debris with a focus on biological responses to wear generated from metal-on-highly crosslinked polyethylene, metal-on-metal, ceramic-on-ceramic, and ceramicon-polyethylene bearings. Articles were selected using criteria designed to identify reports of wear debris particles and biological responses contributing to prosthesis failure. Case reports and articles focused on either clinical outcomes or tribology were excluded. A total of 83 papers met the criteria and were reviewed in detail.

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Characterization of nanoparticle uptake by endothelial cells

Cited by 476 publications

References 29 publications

Drug transport to brain with targeted nanoparticles

Drug transport to brain with targeted nanoparticles

Factors modulating the delivery and effect of enzymatic cargo conjugated with antibodies targeted to the pulmonary endothelium

How Has the Introduction of New Bearing Surfaces Altered the Biological Reactions to Byproducts of Wear and Modularity?

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