Conversion of liposomal 5-fluoro-2′-deoxyuridine and its dipalmitoyl derivative to bile acid conjugates of α-fluoro-β-alanine and their excretion into rat bile

Waalkes, M. Van Borssum; Kuipers, Folkert; Havinga, Rick; Scherphof, Gerrit L.

doi:10.1016/0167-4889(93)90175-o

Cited by 5 publications

(4 citation statements)

References 24 publications

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“…The effects of liposomal formulation on distribution, metabolism, and excretion of encapsulated drugs are well established 3–5 . For example, compared with free doxorubicin, intravenously (i.v.)…”

Section: Introductionmentioning

confidence: 99%

“…The effects of liposomal formulation on distribution, metabolism, and excretion of encapsulated drugs are well-established. − For example, compared with free doxorubicin, intravenously (i.v.) administered liposomal doxorubicin exhibited slower elimination, higher uptake into liver and spleen, and lower uptake into kidney, heart, and lung in rats .…”

Section: Introductionmentioning

confidence: 99%

“…Liposomal formulation also reduced both biliary and urinary excretion of doxorubicin and increased the relative excretion of metabolites. Similarly, encapsulating 5-fluoro-2′-deoxyuridine into liposomes decreased biliary excretion . Liposomal formulation of gadolinium (Gd), a magnetic resonance imaging (MRI) contrast agent, changed the predominant elimination pathways in rats .…”

Section: Introductionmentioning

confidence: 99%

“…Similarly, encapsulating 5-fluoro-2′-deoxyuridine into liposomes decreased biliary excretion. 5 Liposomal formulation of gadolinium (Gd), a magnetic resonance imaging (MRI) contrast agent, changed the predominant elimination pathways in rats. 3 Unlike free Gd contrast agents, liposomal Gd was eliminated mainly through the biliary, instead of the renal system.…”

Section: ■ Introductionmentioning

confidence: 99%

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Polymeric Curcumin Nanoparticle Pharmacokinetics and Metabolism in Bile Duct Cannulated Rats

et al. 2013

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The objective of this study was to compare the pharmacokinetics and metabolism of polymeric nanoparticle encapsulated (nanocurcumin), and solvent solubilized curcumin formulations in Sprague Dawley (SD) rats. Nanocurcumin is currently under development for cancer therapy. Since free, unencapsulated curcumin is rapidly metabolized and excreted in rats, upon i.v. administration of nanocurcumin only nanoparticle encapsulated curcumin can be detected in plasma samples. Hence, the second objective of this study was to utilize the metabolic instability of curcumin to assess in vivo drug release from nanocurcumin. Nanocurcumin and solvent solubilized curcumin were administered at 10 mg curcumin/kg by jugular vein to bile duct-cannulated male SD rats (n = 5). Nanocurcumin increased the plasma Cmax of curcumin 1749 fold relative to the solvent solubilized curcumin. Nanocurcumin also increased the relative abundance of curcumin and glucuronides in bile, but did not dramatically alter urine and tissue metabolite profiles. The observed increase in biliary and urinary excretion of both curcumin and metabolites for the nanocurcumin formulation suggested rapid, “burst” release of curcumin. Although the burst release observed in this study is a limitation for targeted tumor delivery, nanocurcumin still exhibits major advantages over solvent solubilized curcumin, as the nanoformulation does not result in the lung accumulation observed for the solvent solubilized curcumin and increases overall systemic curcumin exposure. Additionally, the remaining encapsulated curcumin fraction following burst release is available for tumor delivery via the enhanced permeation and retention effect commonly observed for nanoparticle formulations.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: ■ Introductionmentioning

confidence: 99%

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Polymeric Curcumin Nanoparticle Pharmacokinetics and Metabolism in Bile Duct Cannulated Rats

et al. 2013

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A new liposomal formulation of Gemcitabine is active in an orthotopic mouse model of pancreatic cancer accessible to bioluminescence imaging

Bornmann

Graeser²,

Esser³

et al. 2007

Cancer Chemother Pharmacol

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Despite its rapid enzymatic inactivation and therefore limited activity in vivo, Gemcitabine is the standard drug for pancreatic cancer treatment. To protect the drug, and achieve passive tumor targeting, we developed a liposomal formulation of Gemcitabine, GemLip (Ø: 36 nm: 47% entrapment). Its anti-tumoral activity was tested on MIA PaCa-2 cells growing orthotopically in nude mice. Bioluminescence measurement mediated by the stable integration of the luciferase gene was employed to randomize the mice, and monitor tumor growth. GemLip (4 and 8 mg/kg), Gemcitabine (240 mg/kg), and empty liposomes (equivalent to 8 mg/kg GemLip) were injected intravenously once weekly for 5 weeks. GemLip (8 mg/kg) stopped tumor growth, as measured via in vivo bioluminescence, reducing the primary tumor size by 68% (SD +/- 8%; p < 0.02), whereas Gemcitabine hardly affected tumor size (-7%; +/- 1.5%). In 80% of animals, luciferase activity in the liver indicated the presence of metastases. All treatments, including the empty liposomes, reduced the metastatic burden. Thus, GemLip shows promising antitumoral activity in this model. Surprisingly, empty liposomes attenuate the spread of metastases similar to Gemcitabine and GemLip. Further, luciferase marked tumor cells are a powerful tool to observe tumor growth in vivo, and to detect and quantify metastases.

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Spontaneously Formed Unilamellar Vesicles

Nieh¹,

Kučerka²,

Katsaras³

2009

Methods in Enzymology

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Conversion of liposomal 5-fluoro-2′-deoxyuridine and its dipalmitoyl derivative to bile acid conjugates of α-fluoro-β-alanine and their excretion into rat bile

Cited by 5 publications

References 24 publications

Polymeric Curcumin Nanoparticle Pharmacokinetics and Metabolism in Bile Duct Cannulated Rats

Polymeric Curcumin Nanoparticle Pharmacokinetics and Metabolism in Bile Duct Cannulated Rats

A new liposomal formulation of Gemcitabine is active in an orthotopic mouse model of pancreatic cancer accessible to bioluminescence imaging

Spontaneously Formed Unilamellar Vesicles

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