Commonly used nonionic surfactants interact differently with the human efflux transporters ABCB1 (p-glycoprotein) and ABCC2 (MRP2)

Hanke, Ulrike; May, Karen; Rozehnal, Veronika; Nagel, Stefan; Siegmund, Werner; Weitschies, Werner

doi:10.1016/j.ejpb.2010.06.008

Cited by 85 publications

(59 citation statements)

References 45 publications

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“…Nanoencapsulation might have avoided or delayed the recognition of TAC by P-gp at the surface of the lymphocytes. 57 Even though polysorbate 80 is able to inhibit P-gp, 58 TAC-LNC and TAC-solution showed different drug efficacy. It is noteworthy that non-encapsulated TAC (TAC-solution) was prepared using polysorbate 80 at the same concentration used in LNC.…”

Section: In Vitro Drug Releasementioning

confidence: 88%

Nanoencapsulation of Tacrolimus in Lipid-Core Nanocapsules Showed Similar Immunosuppressive Activity After Oral and Intraperitoneal Administrations

Friedrich¹,

Dimer²,

Guterres³

et al. 2014

j biomed nanotechnol

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Tacrolimus is widely used in the prophylaxis of solid-organ transplant rejection. Several studies have reported that tacrolimus has variable and poor bioavailability after oral administration, apart from adverse effects such as gastrointestinal disorders, hyperglycemia, nephro-and neurotoxicity. The aim of this work was to encapsulate tacrolimus (TAC) in lipid-core nanocapsules (LNC) as an oral strategy to deliver the drug. To validate our hypothesis, the pharmacodynamic effect of TAC-LNC was determined after oral and intraperitoneal (i.p.) administrations to mice. TAC-LNC had z-average diameter of 210 nm (unimodal), and 99.5% of encapsulation efficiency. In vitro sustained release was determined for TAC-LNC fitting an anomalous transport mechanism (n = 0 8). TAC-LNC demonstrated higher immunosuppressive activity after oral and i.p. administrations, when compared to the drug solution. TAC-LNC administered at 6.0 mg kg −1 day −1 showed equivalent percent reduction in lymphocyte when both routes of administration were used. After oral administration, drug nanoencapsulation allows reducing the dose by at least 40%. Furthermore, the nanoencapsulation of TAC in lipid-core nanocapsules showed pharmacodynamic effect similar for the oral and the i.p. routes. In conclusion, the lipid-core nanocapsules were able to improve the TAC deliver across the oral absorption barrier.

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Section: In Vitro Drug Releasementioning

confidence: 88%

Nanoencapsulation of Tacrolimus in Lipid-Core Nanocapsules Showed Similar Immunosuppressive Activity After Oral and Intraperitoneal Administrations

Friedrich¹,

Dimer²,

Guterres³

et al. 2014

j biomed nanotechnol

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“…These results indicated that the P-gp mediated efflux pump still significantly influenced CsA flux in the AP to BL direction even in presence of Soluplus Ò with concentration range investigated in this study. This is different from the polymers such as Cremophor RH 40, Poloxamer 407, and TPGS, which can inhibit P-gp mediated efflux of drug at relative low concentration [57,58].…”

Section: Csa Transport Across Caco-2 Monolayersmentioning

confidence: 97%

Supersaturated polymeric micelles for oral cyclosporine A delivery

Xia

Zhu

et al. 2013

European Journal of Pharmaceutics and Biopharmaceutics

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“…Immunofluorescence microscopy was performed with the Zeiss Axio Observer.D1 (Carl Zeiss MicroImaging, Jena, Germany). The functionality of the ABCB1-transfected cells was verified by an in vitro accumulation assay using calcein-AM [41]. Stable transfected MDCK2-ABCC2 cells were generated and characterized as described previously [42].…”

Section: Permeability Of Flupirtine and D13223 In Mdck2 Cells Transfementioning

confidence: 99%

Metabolic activation and analgesic effect of flupirtine in healthy subjects, influence of the polymorphic NAT2, UGT1A1 and GSTP1

Siegmund

Modeß

Scheuch

et al. 2015

Brit J Clinical Pharma

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AIMSThe rare association of flupirtine with liver injury is most likely caused by reactive quinone diimines and their oxidative formation may be influenced by the activities of N-acetyltransferases (NAT) that conjugate the less toxic metabolite D13223, and by glucuronosyltransferases (UGT) and glutathione S-transferases (GST) that generate stable terminal glucuronides and mercapturic acid derivatives, respectively. The influence of genetic polymorphisms of NAT2, UGT1A1 and GSTP1 on generation of the terminal mercapturic acid derivatives and analgesic effects was evaluated to identify potential genetic risk factors for hepatotoxicity of flupirtine. METHODSMetabolic disposition of flupirtine was measured after intravenous administration (100 mg), after swallowing an immediate-release (IR) tablet (100 mg) and after repeated administration of modified release (MR) tablets (400 mg once daily 8 days) in 36 selected healthy subjects. Analgesic effects were measured using pain models (delayed onset of muscle soreness, electric pain). RESULTSFlupirtine IR was rapidly but incompletely absorbed (∼72%). Repeated administration of flupirtine MR showed lower bioavailability (∼60%). Approximately 12% of bioavailable flupirtine IR and 8% of bioavailable flupiritine MR was eliminated as mercapturic acid derivatives into the urine independent of the UGT1A1, NAT2 and GSTP1 genotype. Carriers of variant GSTP1 alleles showed lower bioavailability but increased intestinal secretion of flupirtine and increased efficiency in experimental pain. Flupirtine was not a substrate for ABCB1 and ABCC2.

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Commonly used nonionic surfactants interact differently with the human efflux transporters ABCB1 (p-glycoprotein) and ABCC2 (MRP2)

Cited by 85 publications

References 45 publications

Nanoencapsulation of Tacrolimus in Lipid-Core Nanocapsules Showed Similar Immunosuppressive Activity After Oral and Intraperitoneal Administrations

Nanoencapsulation of Tacrolimus in Lipid-Core Nanocapsules Showed Similar Immunosuppressive Activity After Oral and Intraperitoneal Administrations

Supersaturated polymeric micelles for oral cyclosporine A delivery

Metabolic activation and analgesic effect of flupirtine in healthy subjects, influence of the polymorphic NAT2, UGT1A1 and GSTP1

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