Deacylation-Reacylation Cycle: A Possible Absorption Mechanism for the Novel Lymphotropic Antitumor Agent Dipalmitoylphosphatidylfluorouridine in Rats

Sakai, Atsushi; Mori, Nobuhiro; Shuto, Satoshi; Suzuki, Tadakiyo

doi:10.1002/jps.2600820606

Cited by 37 publications

(15 citation statements)

References 15 publications

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“…As supposed, after penetration to cell interior, the active cytotoxic part of modified drug molecule is released by cellular enzymes such as phospholipases, esterases, etc. Also, it is important to accentuate the influence of drug derivatization on the pharmacokinetics: e.g., lipid modification of 5-fluorouridine [9] or N,N'-bis(2-chloroethyl)-N'-nitrosourea [10] led to the acquirement of lymphotropic properties by the derivatives.…”

Section: Discussionmentioning

confidence: 99%

Saccharide‐assisted delivery of cytotoxic liposomes to human malignant cells

et al. 1998

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SUMMARY: The overexpression of lectins by malignant cells was applied for in vitro targeting of liposomes equipped with a saccharide vector and loaded in the lipid phase with a lipid derivative of anticancer agent sarcolysine. The lectin specificity of human leukemia HL-60 and human lung adenocarcinoma ACL cells was revealed by tests with fluorescein-labeled sugar probes. With the help &fluorescent lipid dye it was shown that active saccharide ligands increased the level of the vectored liposome binding to malignant cells by 50-80% as compared to liposomes without vector or with inactive one. The degree of liposome/cell membrane fusion was monitored fluorometrically and was shown to be complete and independent of the vectors. The targeted drugloaded liposomes had the cytotoxic activity 2-4 times higher as compared to the vector-free ones.

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Section: Discussionmentioning

confidence: 99%

Saccharide‐assisted delivery of cytotoxic liposomes to human malignant cells

et al. 1998

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“…In earlier studies, nanometric particulate systems have been developed to target anti-tumour drugs using conventional administration routes (Gregoriadis and Florence, 1991;Maincent et al, 1992;Sakai et al, 1993;Sharma et al, 1996;Videira et al, 2000;Nishioka and Yoshino, 2001). However, after intravenous administration, uptake of colloidal particles by the mononuclear phagocytic system (MPS) reduces circulation time and decreases targeting, thus limiting their application.…”

Section: Introductionmentioning

confidence: 97%

Lymphatic Uptake of Pulmonary Delivered Radiolabelled Solid Lipid Nanoparticles

Videira

Botelho

Santos

et al. 2002

Journal of Drug Targeting

196

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“…Following oral (p.o.) administration of dipalmitoylphosphatidylfluoro-uridine to rats, two major metabolites were identified; a palmitoyl at the 2 position of the glycerol moiety was reacylated by arachidonoyl or linoleoyl (Sakai et al, 1993). Although lymph was found to contain only low levels of prodrug, congeners were detected at very high levels.…”

Section: Introductionmentioning

confidence: 99%

Lymphatic Targeting of Anti-Human Immunodeficiency Virus Nucleosides: Pharmacokinetics of G′-Deoxy-2′,3′-Didehydrothymidine after Intravenous and Oral Administration of Dipalmitoylphosphatidyl Prodrug to Mice

Manouilov

Manouilova

et al. 1997

Antivir Chem Chemother

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The lymphatic system is a primary target for early anti-human immunodeficiency virus drug therapy. Strategies are currently being sought to enhance the delivery of nucleoside analogues such as 3′-deoxy-2′,3′-didehydrothymidine (stavudine; d4T) toward the lymph and lymph nodes. The purpose of this study was to synthesize dipalmitoylphosphatidyl-d4T (DPP-d4T) as a lipophilic prodrug of d4T and to evaluate the lymphatic distribution of d4T following administration of d4T and DPP-d4T to mice. The pharmacokinetics of d4T were characterized following administration of a single intravenous or oral dose of 50 mg kg−1 d4T and an equimolar dose (214 mg kg−1) of DPP-d4T. Concentrations of d4T in serum and lymph nodes were determined by HPLC. Following administration of d4T, the distribution of d4T into lymph nodes was rapid with maximum concentrations observed within 5 min after dosing. The AUC and half-life values of d4T in three groups of lymph nodes were similar to those in serum. Administration of DPP-d4T resulted in significantly lower concentrations of d4T in serum and lymph nodes. Approximately 67% of the intravenously administered DPP-d4T was biotransformed to parent compound. The apparent oral bioavailability of DPP-d4T was low. While the phospholipid prodrug did not increase d4T concentrations in the lymph nodes, it did provide an extended release of the parent nucleoside, resulting in sustained concentrations of d4T.

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Deacylation-Reacylation Cycle: A Possible Absorption Mechanism for the Novel Lymphotropic Antitumor Agent Dipalmitoylphosphatidylfluorouridine in Rats

Cited by 37 publications

References 15 publications

Saccharide‐assisted delivery of cytotoxic liposomes to human malignant cells

Saccharide‐assisted delivery of cytotoxic liposomes to human malignant cells

Lymphatic Uptake of Pulmonary Delivered Radiolabelled Solid Lipid Nanoparticles

Lymphatic Targeting of Anti-Human Immunodeficiency Virus Nucleosides: Pharmacokinetics of G′-Deoxy-2′,3′-Didehydrothymidine after Intravenous and Oral Administration of Dipalmitoylphosphatidyl Prodrug to Mice

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