Pharmacokinetics of intravenously administered stealth liposomal doxorubicin modulated with verapamil in rats

Wang, Jian Cheng; Liu, Xiao Yan; Lu, Wan Liang; Chang, Alex Chia Yu; Zhang, Qiang; Goh, Boon Cher; Lee, How Sung

doi:10.1016/j.ejpb.2005.06.004

Cited by 39 publications

(23 citation statements)

References 21 publications

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“…Similar toxicities for DOX/P(HB-HO) NPs and DOX/FA-PEG-P(HB-HO) NPs were observed compared with those shown in previous studies. It was very obvious that the distribution of DOX in the heart for liposomal DOX preparations was significantly reduced at 0.5 h compared with the free DOX preparations (Wang et al, 2006). Furthermore, significantly lower DOX contents for the DOX micelles and DOX/FOL micelles were detected in the heart than for free DOX at 24 h (Yoo & Park, 2004).…”

Section: Discussionmentioning

confidence: 81%

“…To date, many analysis methods for DOX, such as fluorescence assay (Bibby et al, 2005;Wang et al, 2006), radiolabelled assay (Ogawara et al, 2008), LC/MS assay (Arnold et al, 2004;DiFrancesco et al, 2007), and other methods (Hu et al, 2007;Kim & Wainer, 2010), have been reported. However, several problems may be encountered in these assay methods, such as comparatively difficult procedures, complex compositions of the mobile phases, or high costs in equipment.…”

Section: Discussionmentioning

confidence: 99%

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Quantification of DOX bioavailability in biological samples of mice by sensitive and precise HPLC assay

Zhang

Dong³

et al. 2015

Pharmaceutical Biology

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Results: The t 1/2 values of DOX/P(HB-HO) NPs and DOX/FA-PEG-P(HB-HO) NPs were 2.7-and 3.5-times higher than that of free DOX. No significant difference (p40.05) was found in C max between the NPs and free DOX. The T max values of the two NPs were prolonged from 0.25 to 1 h. The AUC 0-t values were 1.55-and 3.05-folds higher than that of free DOX, and MRT increased to 15.99 h for DOX/P(HB-HO) NPs and 25.14 h for DOX/FA-PEG-P(HB-HO) NPs. For DOX/FA-PEG-P(HB-HO) NPs, the DOX content in the tumors were 10.81-and 3.33-times higher than those for free DOX and DOX/P(HB-HO) NPs at 48 h, respectively. Discussion and conclusions: DOX/FA-PEG-P(HB-HO) NPs displayed reduced cardiac toxicity and improved bioavailability. Moreover, the NPs exhibited a significant extent of DOX accumulation in the tumors, thus suggesting that folate-targeted NPs could effectively transport into HeLa tumors with satisfying targeting.

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Section: Discussionmentioning

confidence: 81%

Section: Discussionmentioning

confidence: 99%

Quantification of DOX bioavailability in biological samples of mice by sensitive and precise HPLC assay

Zhang

Dong³

et al. 2015

Pharmaceutical Biology

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“…Based on the results from transport study of B/W/OA, it was proposed that glucuronides have higher affinity to the basolateral transporters such as MRP1, MRP3, and MRP5, and the efflux of sulfates was mediated by apical transporters such as P-gp, MRP2, and BCRP (50,51). Furthermore, the basolateral to apical transport studies of BG/WG/OAG were conducted in the presence of transporter inhibitors or substrates including verapamil (52,53), MK571 (54,55), EG and ES (56)(57)(58)(59), and MTX (60,61). The results strongly suggested that MRPs and BCRP might be involved in the efflux of conjugated metabolites of the glucuronides.…”

Section: Discussionmentioning

confidence: 99%

Comparison of Intestinal Absorption and Disposition of Structurally Similar Bioactive Flavones in Radix Scutellariae

Zhang

Zhou

et al. 2011

AAPS J

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Abstract. Radix Scutellariae is a commonly used herbal medicine. Baicalein, wogonin, and oroxylin A are three major bioactive flavones in Radix Scutellariae and share similar chemical structures. The intestinal absorption and disposition of baicalein have been systematically investigated by our group before. In this study, the intestinal absorption and disposition of wogonin and oroxylin A were further explored and compared with the profiles of baicalein to find potential structure-activity relationship. Absorptive models including Caco-2 cell monolayer model and rat in situ single-pass intestinal perfusion model as well as in vitro enzymatic kinetic study were employed in the current study. The absorption of baicalein, wogonin, and oroxylin A were favorable with wogonin showing the highest permeability based on two absorptive models. However, three flavones underwent a fast and extensive phase II metabolism. The intestinal metabolism of three flavones exhibited species difference between human and rat. Oroxylin A demonstrated the highest intrinsic clearance of glucuronidation among three flavones. The multidrug resistance proteins might be involved in the efflux of their intracellularly formed conjugated metabolites. The pathway of intestinal absorption and disposition of B, W, and OA was similar. However, the extent of permeability and metabolism was different among three flavones which might be due to the number and position of the hydroxyl group.

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“…Recently, a novel liposomal formulation containing co-loaded doxorubicin (DOX) and verapamil was synthesized and shown to overcome MDR (23,24). The chemosensitizer verapamil chosen in this study, however, was non-specific for P-gp and would cause side effect.…”

Section: Introductionmentioning

confidence: 99%

Co-delivery of Doxorubicin and PSC 833 (Valspodar) by Stealth Nanoliposomes for Efficient Overcoming of Multidrug Resistance

et al. 2012

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-Purpose. This study was aimed at developing co-encapsulated stealth nanoliposomes containing PSC 833, an efficient MDR modulator, and doxorubicin (DOX) in order to increase the effectiveness and decrease adverse effects of the anticancer drug. Methods. In attempt to increase the encapsulation efficiency of drugs, different methods for liposome preparation were tested and the effect of different parameters such as drug to lipid molar ratio, cholesterol mole percent and lipid compositions, were investigated. The final product with a lipid composition of EPC:DSPE-PEG2000:Chol (60:5:30 %mol) was prepared by thin layer film hydration method. After preparation of empty liposomes, DOX and PSC 833 were loaded using ammonium sulfate gradient and remote film loading methods, respectively. Physical characteristics of optimized liposomes (DOX/PSC-L) such as particle size, zeta potential, encapsulation efficiency, in-vitro drugs release and stability were evaluated. Furthermore, in vitro cytotoxicity study of various liposomal formulations as well as drugs, solutions against resistant human breast cancer cell line, T47D/TAMR-6, was evaluated using MTT assay. Results. The best formulation showed a narrow size distribution with average diameter of 91.3 ± 0.2 nm with zeta potential of -6 ± 1.2, the encapsulation efficiency for DOX and PSC 833 were more than 95% and 65.5%, respectively. In DOX-resistant T47D/TAMR-6 cells, dual-agent stealth liposomes showed significantly greater cytotoxicity (P < 0.05) than free DOX and liposomal DOX plus free PSC 833 treatments. Conclusions. Co-encapsulation of DOX and PSC 833 presents a promising anticancer formulation, capable of effective reversal of drug resistance, and should be explored further in therapeutic studies with animal tumor xenograft models.

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Pharmacokinetics of intravenously administered stealth liposomal doxorubicin modulated with verapamil in rats

Cited by 39 publications

References 21 publications

Quantification of DOX bioavailability in biological samples of mice by sensitive and precise HPLC assay

Quantification of DOX bioavailability in biological samples of mice by sensitive and precise HPLC assay

Comparison of Intestinal Absorption and Disposition of Structurally Similar Bioactive Flavones in Radix Scutellariae

Co-delivery of Doxorubicin and PSC 833 (Valspodar) by Stealth Nanoliposomes for Efficient Overcoming of Multidrug Resistance

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