Influence of dendrimer generation and polyethylene glycol length on the biodistribution of PEGylated dendrimers

Kojima, Chie; Regino, Celeste A.S.; Umeda, Yasuhito; Kobayashi, Hisataka; Kono, Kenji

doi:10.1016/j.ijpharm.2009.09.015

Cited by 102 publications

(77 citation statements)

References 20 publications

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“…have intermediate numbers of terminal branches (COO-, OH) [61,62]. Even though dendrimer-based nanoparticles have been extensively researched in the past for their potential to be effective at chemotherapeutic drug delivery into solid tumors [63][64][65][66][67][68][69], including for folate receptor-targeted chemotherapeutic drug delivery [70][71][72][73][74], these investigations have been without emphasis on the optimal size range of 7 to 10 nanometers, the optimal density or the optimal exterior functionalization for effective, passively selective transvascular delivery, without risk of systemic toxicity, biophysical aspects that have important translational implications [1][2][3]7,8,25,26] (Table 1).…”

Section: Reviewmentioning

confidence: 99%

Translational theranostic methodology for diagnostic imaging and the concomitant treatment of malignant solid tumors

Sarin

2015

Neurovascular Imaging

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Pathologic hyperpermeability exists in the spectrum of disease states, including neuro-ischemic, neuro-inflammatory and neuro-oncological. To-date the characterization of disease pathology with T 1 -weighted quantitative dynamic contrast-enhanced magnetic resonance imaging has relied on the study of modeled microvascular parameters such as diseased tissue transvascular flow rates of small molecule paramagnetic imaging agents with short plasma half-lives, based on which it is difficult to assess the specific nature of the disease state. Another type of T 1 -weighted quantitative dynamic contrast-enhanced magnetic resonance imaging involves the use of paramagnetic heavy metal-chelated dendrimer nanoparticles that possess longer plasma half-lives with pre-determined molar relaxivities to quantitatively image concentration of macromolecular contrast agent accumulation over time in hyperpermeable pathology such as solid tumor tissue with the important advantage of concomitantly treating the pathology, which, in recent years, has been shown to be possible with the use of optimally-sized theranostic dendrimer nanoparticles in the 7 to 10 nanometer size range that are functionalized biocompatibly with a small molecule therapeutic. In this focused review, this translational theranostic methodology for quantitative dynamic contrast-enhanced magnetic resonance imaging and the concomitant treatment of malignant solid tumors with optimally designed theranostic nanoparticles within the 7 to 10 nanometer size range is discussed in context of fine-tuning its suitability for the study and treatment of other disease states with pathologic hyperpermeability and without.

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Section: Reviewmentioning

confidence: 99%

Translational theranostic methodology for diagnostic imaging and the concomitant treatment of malignant solid tumors

Sarin

2015

Neurovascular Imaging

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“…Conjugation of active molecules, usually of subnanometer size to a high molecular weight (Mw) carrier, influences drug half-life in the plasma by reducing their elimination in the urine [Gillies et al, 2005]. Since renal filtration is sizedependent, small molecules are cleared faster whereas large particles (e.g., drug-carrier complexes) have extended plasma residence [Sharma and Sharma, 1997;Kojima et al, 2010;Svenson, 2009]. Long-lived complexes can be designed to gradually release active agents, thereby maintaining drug concentrations in the plasma above the minimal therapeutic dose.…”

Section: Reversal Of Drug Resistancementioning

confidence: 99%

Metabolic limitations of the use of nucleoside analogs in cancer therapy may be overcome by application of nanoparticles as drug carriers: A review

Hajdo

Szulc

Klajnert

et al. 2010

Drug Development Research

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Purine and pyrimidine nucleoside analogs (NAs) are antimetabolites commonly used in cancer therapy. Administered as prodrugs, NAs permeate the mambrane using specialized transporters. Following phosphorylation, they interfere with multiple cellular pocessess inducing cytotoxicity. Toxic effects of NAs are dependent on metabolic conversion from a prodrug into the active form. For instance, an exceptionally high activity of deoxycytidine kinase (dCK) in lymphocytes is correlated with a good therapeutic effect of fludarabine in leukemic cells. On the other hand, several studies have shown that nucleoside-transporter (NT)-deficientcells are highly resistant to NAs. Attempts to overcome the metabolic limitations of chemotherapeutics would result in the use of lower drug doses for effective therapy, reduce side effects, and ensure the independence of drug resistance mechanisms. To meet this need, several nanoparticles have been designed to deliver efficently NAs directly to cancer cells. Such vehicles include liposomes, albumins, and dendritic and linear polymers. Therapeutic agents encapsulated or conjugated to nanoparticles have improved pharmacokinetics, solubility, and stability. These factors improve the efficacy of commonly used drugs. Moreover, modification of nanoparticles with targeting molecules such as sugar moieties or folic acid ensures more specific delivery without affecting healthy tissues. Drug Dev Res 71:383-394, 2010.

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“…The understanding of their behaviour in cellular uptake and biodistribution is very helpful to determine the border of their application and the need to introduce modifications in the molecule to improve their mode of action. The circulation time, route of elimination, and organ accumulation strongly depends on dendrimers generation (size), charge and terminal groups [45][46][47]. This knowledge is of prime importance for the rationalization of dendriplexes design and utility, and is evaluated with compounds decorated with chromophore units.…”

Section: Introductionmentioning

confidence: 99%

Fluorescein labelled cationic carbosilane dendritic systems for biological studies

Fuentes‐Paniagua

Serramía

Sánchez‐Nieves

et al. 2015

European Polymer Journal

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Influence of dendrimer generation and polyethylene glycol length on the biodistribution of PEGylated dendrimers

Cited by 102 publications

References 20 publications

Translational theranostic methodology for diagnostic imaging and the concomitant treatment of malignant solid tumors

Translational theranostic methodology for diagnostic imaging and the concomitant treatment of malignant solid tumors

Metabolic limitations of the use of nucleoside analogs in cancer therapy may be overcome by application of nanoparticles as drug carriers: A review

Fluorescein labelled cationic carbosilane dendritic systems for biological studies

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