Studies on pharmacokinetics and tissue distribution of oridonin nanosuspensions

Gao, Lei; Zhang, Dianrui; Chen, Ming‐Hui; Duan, Cunxian; Dai, Wenting; Jia, Lejiao; Zhao, Wenfa

doi:10.1016/j.ijpharm.2007.12.016

Cited by 144 publications

(77 citation statements)

References 24 publications

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“…The nanocrystals might then be recognized as foreign matter and be rapidly cleared by phagocytic cells of MPS which are abundant in special tissues and organs such as liver, spleen, and lung. 30 It has been shown that the uptake of nanoparticles by RES organs following intravenous administration might take anywhere from a few minutes to hours, depending on particle size and composition. 31 Therefore, the paclitaxel nanocrystals in paclitaxel nanosuspension had a markedly higher concentration compared with paclitaxel injection solution in these organs.…”

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confidence: 99%

Formulation and pharmacokinetic evaluation of a paclitaxel nanosuspension for intravenous delivery

Wang¹,

Li²,

Wang³

et al. 2011

IJN

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Paclitaxel is a diterpenoid isolated from Taxus brevifolia . It is effective for various cancers, especially ovarian and breast cancer. Due to its aqueous insolubility, it is administered dissolved in ethanol and Cremophor ® EL (BASF, Ludwigshafen, Germany), which can cause serious allergic reactions. In order to eliminate Cremophor EL, paclitaxel was formulated as a nanosuspension by high-pressure homogenization. The nanosuspension was lyophilized to obtain the dry paclitaxel nanoparticles (average size, 214.4 ± 15.03 nm), which enhanced both the physical and chemical stability of paclitaxel nanoparticles. Paclitaxel dissolution was also enhanced by the nanosuspension. Differential scanning calorimetry showed that the crystallinity of paclitaxel was preserved during the high-pressure homogenization process. The pharmacokinetics and tissue distribution of paclitaxel were compared after intravenous administration of paclitaxel nanosuspension and paclitaxel injection. In rat plasma, paclitaxel nanosuspension exhibited a significantly ( P < 0.01) reduced area under the concentration curve (AUC) 0–∞ (20.343 ± 9.119 μg · h · mL −1 vs 5.196 ± 1.426 μg · h · mL −1 ), greater clearance (2.050 ± 0.616 L · kg −1 · h −1 vs 0.556 ± 0.190 L · kg −1 · h −1 ), and shorter elimination half-life (5.646 ± 2.941 vs 3.774 ± 1.352 hours) compared with the paclitaxel solution. In contrast, the paclitaxel nanosuspension resulted in a significantly greater AUC 0–∞ in liver, lung, and spleen (all P < 0.01), but not in heart or kidney.

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confidence: 99%

Formulation and pharmacokinetic evaluation of a paclitaxel nanosuspension for intravenous delivery

Wang¹,

Li²,

Wang³

et al. 2011

IJN

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“…49,50 For instance, the oridonin nanosuspensions, with a zeta potential value of -21.8 mV, developed by Gao et al demonstrated a high uptake by the liver and spleen. 49 Rabinow et al evaluated the biodistribution of an intravenous itraconazole nanosuspension (with a zeta potential of -30.6 mV) and found that high accumulation of the drug occurred in the liver and spleen. 50 In vitro release study showed that drug release from the nanocrystals was rapid and was comparable to that from cosolvent ( Figure 3D).…”

Section: Discussionmentioning

confidence: 99%

Elucidating the in vivo fate of nanocrystals using a physiologically based pharmacokinetic model: a case study with the anticancer agent SNX-2112

Dong

Wang

et al. 2015

IJN

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Introduction SNX-2112 is a promising anticancer agent but has poor solubility in both water and oil. In the study reported here, we aimed to develop a nanocrystal formulation for SNX-2112 and to determine the pharmacokinetic behaviors of the prepared nanocrystals. Methods Nanocrystals of SNX-2112 were prepared using the wet-media milling technique and characterized by particle size, differential scanning calorimetry, drug release, etc. Physiologically based pharmacokinetic (PBPK) modeling was undertaken to evaluate the drug’s disposition in rats following administration of drug cosolvent or nanocrystals. Results The optimized SNX-2112 nanocrystals (with poloxamer 188 as the stabilizer) were 203 nm in size with a zeta potential of −11.6 mV. In addition, the nanocrystals showed a comparable release profile to the control (drug cosolvent). Further, the rat PBPK model incorporating the parameters of particulate uptake (into the liver and spleen) and of in vivo drug release was well fitted to the experimental data following administration of the drug nanocrystals. The results reveal that the nanocrystals rapidly released drug molecules in vivo, accounting for their cosolvent-like pharmacokinetic behaviors. Due to particulate uptake, drug accumulation in the liver and spleen was significant at the initial time points (within 1 hour). Conclusion The nanocrystals should be a good choice for the systemic delivery of the poorly soluble drug SNX-2112. Also, our study contributes to an improved understanding of the in vivo fate of nanocrystals.

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“…Oridonin and oridonin nanosuspension solution were prepared as described previously; 15 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and dimethyl sulfoxide were purchased from Sigma-Aldrich (St Louis, MO). Fetal bovine serum was purchased from TBD Biotechnology Development (Tianjin, China).…”

Section: Materials and Methods Materialsmentioning

confidence: 99%

“…A previous study showed that oridonin nanosuspension, possessing a significantly increased solubility and dissolution rate than free oridonin, could markedly induce oridonin molecular concentration around the cells. 15 Apart from this, the small size of nanosuspension may facilitate its adhesion to the cells and improve the interactions between the cells and drugs. Moreover, it is generally considered that nanoparticles can be nonspecically internalized into cells via endocytosis or phagocytosis.…”

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Oridonin nanosuspension was more effective than free oridonin on G2/M cell cycle arrest and apoptosis in the human pancreatic cancer PANC-1 cell line

Qi¹,

Zhang²,

Xu³

et al. 2012

IJN

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Oridonin, a diterpenoid isolated from Rabdosia rubescencs, has been reported to have antitumor effects. However, low solubility has limited its clinical applications. Preparation of drugs in the form of nanosuspensions is an extensively utilized protocol. In this study, we investigated the anticancer activity of oridonin and oridonin nanosuspension on human pancreatic carcinoma PANC-1 cells. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was performed to investigate the effect of oridonin on cell growth. Propidium iodide and Hoechst 33342 staining were used to detect morphologic changes. The percentage of apoptosis and cell cycle progression was determined by flow cytometric method staining with propidium iodide. Annexin V-fluorescein isothiocyanate (FITC)/PI staining was used to evaluate cell apoptosis by flow cytometry. Caspase-3 activity was measured by spectrophotometry. The apoptotic and cell cycle protein expression were determined by Western blot analysis. Both oridonin and oridonin nanosuspension induced apoptosis and G 2 /M phase cell cycle arrest, and the latter had a more significant cytotoxic effect. The ratio of Bcl-2/Bax protein expression was decreased and caspase-3 activity was stimulated. The expression of cyclin B1 and p-cdc2 (T161) was suppressed. Our results showed that oridonin nanosuspension was more effective than free oridonin on G 2 /M cell cycle arrest and apoptosis in the human pancreatic cancer PANC-1 cell line.

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Studies on pharmacokinetics and tissue distribution of oridonin nanosuspensions

Cited by 144 publications

References 24 publications

Formulation and pharmacokinetic evaluation of a paclitaxel nanosuspension for intravenous delivery

Formulation and pharmacokinetic evaluation of a paclitaxel nanosuspension for intravenous delivery

Elucidating the in vivo fate of nanocrystals using a physiologically based pharmacokinetic model: a case study with the anticancer agent SNX-2112

Oridonin nanosuspension was more effective than free oridonin on G2/M cell cycle arrest and apoptosis in the human pancreatic cancer PANC-1 cell line

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Studies on pharmacokinetics and tissue distribution of oridonin nanosuspensions

Cited by 144 publications

References 24 publications

Formulation and pharmacokinetic evaluation of a paclitaxel nanosuspension for intravenous delivery

Formulation and pharmacokinetic evaluation of a paclitaxel nanosuspension for intravenous delivery

Elucidating the in vivo fate of nanocrystals using a physiologically based pharmacokinetic model: a&nbsp;case study with the anticancer agent SNX-2112

Oridonin nanosuspension was more effective than free oridonin on G2/M cell cycle arrest and apoptosis in the human pancreatic cancer PANC-1 cell line

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Elucidating the in vivo fate of nanocrystals using a physiologically based pharmacokinetic model: a case study with the anticancer agent SNX-2112