Liposomal Entrapment of Floxuridine

Simmons, Stephen P.; Kramer, Paul A.

doi:10.1002/jps.2600660720

Cited by 15 publications

(5 citation statements)

References 10 publications

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“…Beside these higher plasma levels, sustained exposure to the drug was achieved, as liposomal d-Ino remained fully detectable 2 h after administration, whereas free d-Ino was totally cleared. Despite its extremely widespread use in clinical oncology, few reports have focused on encapsulating 5-FU in simple carriers, probably as a result of its polar and amphotereous properties that render it particularly difficult to entrap in standard liposomes (Simmons and Krame, 1977;Nii and Ishii, 2005). However, as a prodrug, 5-FU presents an opportunity to increase its therapeutic efficacy by combining it with biochemical modulators that can improve its intratumoural activation pattern.…”

Section: Discussionmentioning

confidence: 99%

In vitro and in vivo reversal of resistance to 5-fluorouracil in colorectal cancer cells with a novel stealth double-liposomal formulation

Fanciullino¹,

Giacometti²,

Mercier³

et al. 2007

Br J Cancer

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Drug resistance is a major cause of treatment failure in cancer chemotherapy, including that with the extensively prescribed antimetabolite, 5-fluorouracil (5-FU). In this study, we tried to reverse 5-FU resistance by using a double-punch strategy: combining 5-FU with a biochemical modulator to improve its tumoural activation and encapsulating both these agents in one same stealth liposome. Experiments carried out in the highly resistant, canonical SW620 human colorectal model showed a up to 80% sensitisation to 5-FU when these cells were treated with our liposomal formulation. Results with this formulation demonstrated 30% higher tumoural drug uptake, better activation with increased active metabolites including critical-5-fluoro-2-deoxyuridine-5-monophosphate, superior inhibition (98%) of tumour thymidylate synthase, and subsequently, higher induction of both early and late apoptosis. Drug monitoring showed that higher and sustained exposure was achieved in rats treated with liposomal formulation. When examined in a xenograft animal model, our dual-agent liposomal formulation caused a 74% reduction in tumour size with a mean doubling in survival time, whereas standard 5-FU failed to exhibit significant antiproliferative activity as well as to increase the lifespan of tumour-bearing mice. Taken collectively, our data suggest that resistance to 5-FU can be overcome through a better control of its intratumoural activation and the use of an encapsulated formulation.

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Section: Discussionmentioning

confidence: 99%

In vitro and in vivo reversal of resistance to 5-fluorouracil in colorectal cancer cells with a novel stealth double-liposomal formulation

Fanciullino¹,

Giacometti²,

Mercier³

et al. 2007

Br J Cancer

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“…Liposomes were then suspended in distilled water ; Figure 1 illustrates the release results. There was an initial rapid release of 5-FU, after which the data plateau ; 80 % of entrapped drug was lost (see also Simmons & Kramer 1977). Kinetics were first-order only at the early stage.…”

Section: Drug Release From Liposomesmentioning

confidence: 90%

Skin delivery of 5-fluorouracil from ultradeformable and standard liposomes in-vitro

Maghraby

Williams

Barry

2001

Journal of Pharmacy and Pharmacology

185

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The potential use of ultradeformable and standard liposomes as skin drug delivery systems was investigated in-vitro. An improved experimental design gave a good measure for skin deposition of drug. This avoided the contamination that can occur due to incomplete washing of the donor before direct determination of the amount of drug in the skin. The design used aqueous ethanolic receptor which is believed to diffuse into skin, disrupting deposited liposomes (if any) and thus releasing both bound and free drug. The receptor fluid was refined by testing different concentrations of ethanol. The applied dose was also optimized. Using the improved design and the optimum dose, an ultradeformable formulation was compared with four traditional liposomes for skin delivery of 5-fluorouracil (5-FU). The best receptor was 50% aqueous ethanol and the optimum dose was 20 microL. The ultradeformable formulation was superior to standard liposomes in the skin delivery of 5-FU. Of the traditional liposomes, the non-rigid preparation was the best. However, stabilization of the liposome membrane with cholesterol abolished the benefit of this non-rigid preparation. It was concluded that ultradeformable vesicles are promising agents for skin delivery of drugs.

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“…In addition, due to the amide linkage in its backbone, sphingomyelin is also less sensitive to pH‐dependent hydrolysis when compared to the relatively more sensitive ester linkages of most diacylphospholipids 123. Importantly, formulations composed of sphingomyelin have been used to stabilize liposomes loaded with a wide range of drug molecules; including floxuridine,162 vincristine (Fig. 6A and B),72, 144, 163 vinblastine,10 vinorelbine,10, 164 topotecan,15 and ciprofloxacin 165.…”

Section: Control Of In Vivo Drug Release Ratesmentioning

confidence: 99%

Pharmacokinetics and in vivo drug release rates in liposomal nanocarrier development

Drummond

Noble

Hayes

et al. 2008

Journal of Pharmaceutical Sciences

252

217

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Liposomal Entrapment of Floxuridine

Cited by 15 publications

References 10 publications

In vitro and in vivo reversal of resistance to 5-fluorouracil in colorectal cancer cells with a novel stealth double-liposomal formulation

In vitro and in vivo reversal of resistance to 5-fluorouracil in colorectal cancer cells with a novel stealth double-liposomal formulation

Skin delivery of 5-fluorouracil from ultradeformable and standard liposomes in-vitro

Pharmacokinetics and in vivo drug release rates in liposomal nanocarrier development

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