Microspheres for targeting drugs to specific body sites

Davis, S.S.; Ilium, Lisbeth; Moghimi, S. Moein; Davies, Martyn C.; Porter, Christopher John; Muir, I. S.; Brindley, Anne; Christy, N. M.; Norman, Maria E.; Williams, Paul; Dunn, Susan E.

doi:10.1016/0168-3659(93)90175-5

Cited by 77 publications

(29 citation statements)

References 17 publications

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“…The lower size limit (15 nm) is defined by the pore size of the kidneys 42 and the upper size limit (150 nm) by the pore size of the liver, 42 the clathrin-mediated endocytosis pathway, 87 and the bone marrow uptake. 43 Outside this size range, it has to be expected that the uptake rate of one or more organs is altered; for example, the direct passage of very small NPs (,15 nm) through the pores of the organ blood capillaries. In fact, the lower and higher size limits might be slightly lower, due to the formation of a "protein corona" in vivo and, hence, increased particle diameter.…”

Section: Distribution and Excretionmentioning

confidence: 99%

“…66,67,93,95 Studies with polystyrene and iron oxide NPs showed that the bone marrow plays an important role in the clearance of NPs. [43][44][45] Therefore, for our nanosilver PBPK models we assumed that NPs are cleared from the blood by the bone marrow. Nevertheless, the possibility that the small recovery in the study by Lankveld et al 26 is due to, for example, absorption of NPs into the wall of the storage bottle and, hence, a lower injected dose is realized or due to the distribution of the particles in other parts of the body cannot be excluded.…”

mentioning

confidence: 99%

“…[43][44][45] Therefore, it was assumed that all particles that are not taken up by other organs or are excreted are absorbed by the bone marrow.…”

mentioning

confidence: 99%

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A physiologically based pharmacokinetic model for ionic silver and silver nanoparticles

Bachler

Goetz

Konrad³

2013

IJN

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Silver is a strong antibiotic that is increasingly incorporated into consumer products as a bulk, salt, or nanosilver, thus potentially causing side-effects related to human exposure. However, the fate and behavior of (nano)silver in the human body is presently not well understood. In order to aggregate the existing experimental information, a physiologically based pharmacokinetic model (PBPK) was developed in this study for ionic silver and nanosilver. The structure of the model was established on the basis of toxicokinetic data from intravenous studies. The number of calibrated parameters was minimized in order to enhance the predictive capability of the model. We validated the model structure for both silver forms by reproducing exposure conditions (dermal, oral, and inhalation) of in vivo experiments and comparing simulated and experimentally assessed organ concentrations. Therefore, the percutaneous, intestinal, or pulmonary absorption fraction was estimated based on the blood silver concentration of the respective experimental data set. In all of the cases examined, the model could successfully predict the biodistribution of ionic silver and 15-150 nm silver nanoparticles, which were not coated with substances designed to prolong the circulatory time (eg, polyethylene glycol). Furthermore, the results of our model indicate that: (1) within the application domain of our model, the particle size and coating had a minor influence on the biodistribution; (2) in vivo, it is more likely that silver nanoparticles are directly stored as insoluble salt particles than dissolve into Ag + ; and (3) compartments of the mononuclear phagocytic system play a minor role in exposure levels that are relevant for human consumers. We also give an example of how the model can be used in exposure and risk assessments based on five different exposure scenarios, namely dietary intake, use of three separate consumer products, and occupational exposure.

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Section: Distribution and Excretionmentioning

confidence: 99%

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confidence: 99%

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A physiologically based pharmacokinetic model for ionic silver and silver nanoparticles

Bachler

Goetz

Konrad³

2013

IJN

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“…Biodegradable nanoparticles have been extensively investigated in drug delivery systems. [16][17][18] Due to their small particle size, they are attracted to their target tissues and have the advantages of targeted drug delivery to the desired site of action, prolonged blood circulation of the encapsulated drug, and reduced drug side effects. [19][20][21] We also investigated the physicochemical properties of PLGA nanoparticles incorporating celecoxib, and their antitumor activity was studied using glioma cell lines.…”

Section: Introductionmentioning

confidence: 99%

Preparation of polylactide-co-glycolide nanoparticles incorporating celecoxib and their antitumor activity against brain tumor cells

Kim

Jeong²,

Jin³

et al. 2011

IJN

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Background: Celecoxib, a cyclo-oxygenase (COX)-2 inhibitor, has been reported to mediate growth inhibitory effects and to induce apoptosis in various cancer cell lines. In this study, we examined the potential effects of celecoxib on glioma cell proliferation, migration, and inhibition of COX-2 expression in vitro. Methods: Celecoxib was incorporated into poly DL-lactide-co-glycolide (PLGA) nanoparticles for antitumor drug delivery. Results: PLGA nanoparticles incorporating celecoxib had spherical shapes and their particle sizes were in the range of 50-200 nm. Drug-loading efficiency was not significantly changed according to the solvent used, except for acetone. Celecoxib was released from the PLGA nanoparticles for more than 2 days, and the higher the drug content, the longer the duration of drug release. PLGA nanoparticles incorporating celecoxib showed cytotoxicity against U87MG tumor cells similar to that of celecoxib administered alone. Furthermore, celecoxib did not affect the degree of migration of U87MG cells. PLGA nanoparticles incorporating celecoxib showed dose-dependent cytotoxicity similar to that of celecoxib alone in C6 rat glioma cells. Western blot assay of the C6 cells showed that neither celecoxib alone nor PLGA nanoparticles incorporating celecoxib affected COX-2 expression. Conclusion: PLGA nanoparticles incorporating celecoxib had antitumor activity similar to that of celecoxib alone, even though these particles did not affect the degree of migration or COX-2 expression in the tumor cells.

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“…For some diagnostic applications, such as percutaneous lymphography, the administration of diagnostic particulates of a significantly smaller size is required (Torchilin, 1999). An experiment using polystyrene nanospheres showed that particulate uptake in the primary lymph node after subcutaneous injection is drastically increased when nanospheres having a diameter of less than 100 nm were used (Davis et al, 1993).…”

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confidence: 99%

Polymeric micelles and molecular modeling applied to the development of radiopharmaceuticals

Grallert

Rangel-Yagui

Pasqualoto

et al. 2012

Braz. J. Pharm. Sci.

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Micelles composed of amphiphilic copolymers linked to a radioactive element are used in nuclear medicine predominantly as a diagnostic application. A relevant advantage of polymeric micelles in aqueous solution is their resulting particle size, which can vary from 10 to 100 nm in diameter. In this review, polymeric micelles labeled with radioisotopes including technetium (99mTc) and indium (111In), and their clinical applications for several diagnostic techniques, such as single photon emission computed tomography (SPECT), gamma-scintigraphy, and nuclear magnetic resonance (NMR), were discussed. Also, micelle use primarily for the diagnosis of lymphatic ducts and sentinel lymph nodes received special attention. Notably, the employment of these diagnostic techniques can be considered a significant tool for functionally exploring body systems as well as investigating molecular pathways involved in the disease process. The use of molecular modeling methodologies and computer-aided drug design strategies can also yield valuable information for the rational design and development of novel radiopharmaceuticals.
Micelas poliméricas compostas de copolímeros ligadas a um elemento radioativo são utilizadas em Medicina Nuclear com aplicação predominantemente diagnóstica. A vantagem relevante da utilização de micelas poliméricas em solução aquosa é o tamanho de suas partículas, as quais podem variar de 10 a 100 nm de diâmetro. Neste trabalho de revisão são apresentadas micelas poliméricas marcadas com radioisotopos, como tecnécio-99m (99mTc) e índio-111 (111In), assim como suas aplicações clínicas em técnicas de diagnóstico como Tomografia por emissão de Fóton Único (Single photon Emission Computed Tomography - SPECT), cintilografia, e Ressonância Magnética Nuclear (RMN). Neste contexto, sua aplicação em diagnóstico de sistema linfático e linfonodo sentinela recebe atenção especial. O emprego de técnicas de diagnóstico pode ser considerado uma ferramenta importante para a exploração de sistemas no organismo humano assim como para a investigação de caminhos moleculares envolvidos nos processos de diversas doenças. O uso de metodologias de modelagem molecular e estratégias de desenvolvimento de fármacos assistidas computacionalmente também pode fornecer informações valiosas para o planejamento e o desenvolvimento racional de novos radiofármacos

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Microspheres for targeting drugs to specific body sites

Cited by 77 publications

References 17 publications

A physiologically based pharmacokinetic model for ionic silver and silver nanoparticles

A physiologically based pharmacokinetic model for ionic silver and silver nanoparticles

Preparation of polylactide-co-glycolide nanoparticles incorporating celecoxib and their antitumor activity against brain tumor cells

Polymeric micelles and molecular modeling applied to the development of radiopharmaceuticals

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