Carrier and dose effects on the pharmacokinetics of T-0128, a camptothecin analogue-carboxymethyl dextran conjugate, in non-tumor- and tumor-bearing rats

Harada, Mitsunori; Murata, Junichi; Sakamura, Yumi; Sakakibara, Hiroyuki; Okuno, Satoshi; Suzuki, Takehiko

doi:10.1016/s0168-3659(00)00372-2

Cited by 41 publications

(22 citation statements)

References 22 publications

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“…3). [166][167][168][169][170][171][172][173][174][175]. (B) Comparison of the ratio of free to nanoconstruct associated drugs in various tissues normalized across studies as % of injected dose per gram of tissue.…”

Section: Biocompatibilitymentioning

confidence: 99%

Anticancer nanomedicine and tumor vascular permeability; Where is the missing link?

Taurin

Nehoff

Greish

2012

Journal of Controlled Release

287

207

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Section: Biocompatibilitymentioning

confidence: 99%

Anticancer nanomedicine and tumor vascular permeability; Where is the missing link?

Taurin

Nehoff

Greish

2012

Journal of Controlled Release

287

207

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“…Dextran derivative is one of the frequently used macromolecular carriers for the delivery of drugs (Yura et al 1999;Harada et al 2001) because of its relatively low immunogenicity and long experience in clinical use as a plasma expander (Larson 1989;Mehvar 2000). Conjugation of drugs to dextran, by altering the in vivo behavior of drugs, may enhance the therapeutic ef cacy and reduce the toxicity of drugs (Hattori et al 2000).…”

Section: Effect Of Chemical Modification On the Pharmacokinetics And mentioning

confidence: 99%

Effect of Chemical Modification on the Pharmacokinetics and Biodistribution of Carboxymethyl Dextran as a Drug Carrier

2002

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The in vivo fate of drugs conjugated to macromolecules inevitably depends on that of macromolecules. However, the in vivo fate of macromolecules also may be altered by conjugation to drugs. For the efficient design of carboxymethyldextran (CMD) conjugates of a new analgesic drug, DA5018, we investigated whether the chemical modifications alter the pharmacokinetics and tissue distribution of CMD itself. [(14)C]CMD, oxidized [(14)C]CMD ([(14)C]OCMD), [(14)C]OCMD conjugates of DA5018 ([(14)C]OCMD-DA5018) and [(14)C]OCMD conjugates of ethanolamine ([(14)C]OCMD-EA) were prepared and their molecular sizes were compared by size exclusion HPLC. The pharmacokinetics, biliary excretion, and tissue distribution of total radioactivity were compared after intravenous administration of each CMD derivative, 2.0 MBq/kg, to rats. The effective molecular sizes of CMD derivatives decreased in the order of [(14)C]CMD, [(14)C]OCMD-DA5018, [(14)C]OCMD, and [(14)C]OCMD-EA. After administration of each derivative, the mean AUC values of total radioactivity decreased with the decrease in the effective molecular size. The values of CL, Vss, and the amount of total radioactivity excreted in 24-hr urine increased considerably with the decrease in the effective molecular size. The tissue-to-plasma ratios of total radioactivity remaining in heart, liver, lung, kidney, and spleen at 24 hr also increased in the opposite order of the effective molecular size. Taken together, all these results demonstrate that the chemical modifications and physicochemical properties of attached chemicals can alter the pharmacokinetics and tissue distribution of CMD. One possible reason might be the difference in the effective molecular size of various CMD derivatives. Our study demonstrates that it may be necessary to consider the effect of chemical modification on the in vivo fate of macromolecules in designing macromolecular drug conjugates.

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“…34 Chemical or physical conjugation of therapeutic agents with the polysaccharide derivatives increased the biological stability in blood circulation and consequently prolong the time period of activity. [35][36][37][38] On the other hand, polysaccharides have been used to target the agents to the tumor (passive targeting) [39][40][41][42] or the liver (active targeting). [43][44][45] In addition, paramagnetic or radiolabeled polysacchrides have been applied for diagnostic imaging.…”

Section: Introductionmentioning

confidence: 99%

Promoted Adipogenesis of Rat Mesenchymal Stem Cells by Transfection of Small Interfering RNA Complexed with a Cationized Dextran

Nagane

Tabata

2010

Tissue Engineering Part A

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The objective of this study is to investigate the possibility of small interfering RNA (siRNA) complexed with a cationized dextran of nonviral carrier to biologically modify the adipogenesis extent of bone marrow-derived mesenchymal stem cells (MSC). Spermine was chemically introduced to the hydroxyl groups of dextran to prepare the cationized dextran (spermine-dextran). The spermine-dextran could form a complex with siRNA, and the physicochemical properties were changed by the molecular weight of dextran, the molar percentage of spermine introduced to dextran, and the molar ratio of nitrogen molecule of spermine-dextran to the phosphorous ones of siRNA (N/P ratio). The gene expression level of luciferase or green fluorescence protein was significantly suppressed by transfection with the complex of spermine-dextran and siRNA. The gene expression level by the complex decreased with an increase in the extent of complex internalized. Biochemical experiments revealed that culture in an adipogenic differentiation medium allowed MSC to differentiate into adipogenic cells. However, upon culturing with siRNA of anti-transcription coactivator containing PDZ-binding motif (TAZ) for osteogenic differentiation complexed with the spermine-dextran, the adipogenesis of MSC was further promoted. It is concluded that the spemine-dextran was a promising nonviral carrier to suppress the expression level of differentiation gene, resulting in the modification of cell differentiation direction.

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Carrier and dose effects on the pharmacokinetics of T-0128, a camptothecin analogue-carboxymethyl dextran conjugate, in non-tumor- and tumor-bearing rats

Cited by 41 publications

References 22 publications

Anticancer nanomedicine and tumor vascular permeability; Where is the missing link?

Anticancer nanomedicine and tumor vascular permeability; Where is the missing link?

Effect of Chemical Modification on the Pharmacokinetics and Biodistribution of Carboxymethyl Dextran as a Drug Carrier

Promoted Adipogenesis of Rat Mesenchymal Stem Cells by Transfection of Small Interfering RNA Complexed with a Cationized Dextran

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