Silybin and its bioavailable phospholipid complex (IdB 1016) potentiate in vitro and in vivo the activity of cisplatin

Giacomelli, Sabrina; Gallo, Daniela; Apollonio, Patrizia; Ferlini, Cristiano; Distefano, Mariagrazia; Morazzoni, Paolo; Riva, Antonella; Bombardelli, Ezio; Mancuso, Salvatore; Scambia, Giovanni

doi:10.1016/s0024-3205(01)01511-9

Cited by 69 publications

(47 citation statements)

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“…Repeated daily administration of silipide by oral gavage (at 450 mg/kg silipide, equivalent to 180 mg/kg silibinin) caused inhibition of ovarian tumor growth in nude mice, and levels of silibinin in the plasma and tumor after termination of the experiment were 15 Amol/L (7.2 Ag/mL) and 0.38 nmol/g (0.2 Ag/g) tissue, respectively (34). Furthermore, silipide at a dose of 1,800 mg/kg (equivalent to 720 mg/kg silibinin) given concomitantly with chemotherapy enhanced the antitumor activity of cis-platinum in a nude mouse model bearing the human A2780 ovarian cancer (35). Levels of silibinin in human colorectal and liver tissue have not been described previously, although silibinin-containing remedies have long been marketed as liver protectants.…”

Section: Discussionmentioning

confidence: 93%

Pilot Study of Oral Silibinin, a Putative Chemopreventive Agent, in Colorectal Cancer Patients: Silibinin Levels in Plasma, Colorectum, and Liver and Their Pharmacodynamic Consequences

Hoh

Boocock

Marczylo

et al. 2006

Clinical Cancer Research

152

141

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Silibinin, a flavonolignan from milk thistle, has intestinal cancer chemopreventive efficacy in rodents. It is a strong antioxidant and modulates the insulin-like growth factor (IGF) system by increasing circulating levels of IGF-binding protein 3 (IGFBP-3) and decreasing levels of IGF-I.Here, the hypothesis was tested that administration of oral silibinin generates agent levels in human blood and colorectal and hepatic tissues consistent with pharmacologic activity. Patients with confirmed colorectal adenocarcinoma received silibinin formulated with phosphatidylcholine (silipide) at dosages of 360, 720, or 1,440 mg silibinin daily for 7 days. Blood and biopsy samples of normal and malignant colorectum or liver were obtained before dosing, and blood and colorectal or hepatic tissues were collected at resection surgery after the final silipide dose. Levels of silibinin were quantified by high-pressure liquid chromatography-UV, and plasma metabolites were identified by liquid chromatography-mass spectrometry. Blood levels of IGFBP-3, IGF-I, and the oxidative DNA damage pyrimidopurinone adduct of deoxyguanosine (M 1 dG) were determined. Repeated administration of silipide was safe and achieved levels of silibinin of 0.3 to 4 Amol/L in the plasma, 0.3 to 2.5 nmol/g tissue in the liver, and 20 to 141nmol/g tissue in colorectal tissue. Silibinin monoglucuronide, silibinin diglucuronide, silibinin monosulfate, and silibinin glucuronide sulfate were identified in the plasma. Intervention with silipide did not affect circulating levels of IGFBP-3, IGF-I, or M 1 dG. The high silibinin levels achieved in the human colorectal mucosa after consumption of safe silibinin doses support its further exploration as a potential human colorectal cancer chemopreventive agent.

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Section: Discussionmentioning

confidence: 93%

Pilot Study of Oral Silibinin, a Putative Chemopreventive Agent, in Colorectal Cancer Patients: Silibinin Levels in Plasma, Colorectum, and Liver and Their Pharmacodynamic Consequences

Hoh

Boocock

Marczylo

et al. 2006

Clinical Cancer Research

152

141

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“…Even under in vivo conditions, silipide was able to significantly enhance the anti-tumor activity of CDDP measured in terms of TWI % and log10cell kill(LCK) values. Importantly, mice receiving the combination therapy recovered from weight loss earlier to the ones receiving CCDP alone (Giacomelli et al, 2002).…”

Section: Ovarian Cancermentioning

confidence: 96%

Silymarin and epithelial cancer chemoprevention: How close we are to bedside?

Kaur

Agarwal

2007

Toxicology and Applied Pharmacology

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Failure and high systemic toxicity of conventional cancer therapies have accelerated the focus on the search for newer agents, which could prevent and/or slow-down cancer growth and have more human acceptability by being less or non-toxic. Silymarin is one such agent, which has been extensively used since ages for the treatment of liver conditions, and thus has possibly the greatest patient acceptability. In recent years, increasing body of evidence has underscored the cancer preventive efficacy of silymarin in both in vitro and in vivo animal models of various epithelial cancers. Apart from chemopreventive effects, other noteworthy aspects of silymarin and its active constituent silibinin in cancer treatment include their capability to potentiate the efficacy of known chemotherapeutic drugs, as an inhibitor of multidrug resistance associated proteins, and as an adjunct to the cancer therapeutic drugs due to their organ-protective efficacy specifically liver, and immunostimulatory effects. Widespread use of silymarin for liver health in humans and commercial availability of its formulations with increased bioavailability, further underscore the necessity of carrying out controlled clinical trials with these agents in cancer patients. In this review, we will briefly discuss the outcomes of clinical trials being conducted by us and others in cancer patients to provide insight into the clinical relevance of the observed chemopreventive effects of these agents in various epithelial cancer models.

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“…Phytosome technology has been considered to be a major advancement in clinical research for active phyto-constituents with poor bioavailability (5)(6)(7). Indeed, the solubility and bioavailability of several therapeutic candidates may be greatly enhanced by phytosome technology (8).…”

Section: Introductionmentioning

confidence: 99%

Design and Evaluation of a Novel Evodiamine-Phospholipid Complex for Improved Oral Bioavailability

et al. 2012

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Abstract. A novel evodiamine (EVO)-phospholipid complex (EPLC) was designed to improve the bioavailability of EVO. A central composite design approach was employed for process optimization. EPLC were characterized by differential scanning calorimetry, ultraviolet spectroscopy, Fourier transformed infrared spectroscopy, 1 H-NMR spectroscopy, matrix-assisted laser desorption/ionization time-offlight spectroscopy, apparent solubility, and dissolution rate. After oral administration of EPLC, the concentrations of EVO at different time points were determined by high-performance liquid chromatography. The optimal formulation for EPLC was obtained where the values of X 1 , X 2 , and X 3 were 2, 0.5, and 2.5 mg/mL, respectively. The average particle size and zeta potential of EPLC with the optimized formulation were 246.1 nm and −26.94 mV, respectively. The EVO and phospholipids in the EPLC were associated with non-covalent interactions. The solubility of EPLC in water and the dissolution rate of EPLC in phosphate-buffered solution (pH 6.8) were substantially enhanced. The plasma EVO concentration-time curves of EPLC and free EVO were both in accordance with the two-compartment model. The peak concentration and AUC 0−∞ of EPLC were increased, and the relative bioavailability was significantly increased to 218.82 % compared with that of EVO.

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Silybin and its bioavailable phospholipid complex (IdB 1016) potentiate in vitro and in vivo the activity of cisplatin

Cited by 69 publications

References 0 publications

Pilot Study of Oral Silibinin, a Putative Chemopreventive Agent, in Colorectal Cancer Patients: Silibinin Levels in Plasma, Colorectum, and Liver and Their Pharmacodynamic Consequences

Pilot Study of Oral Silibinin, a Putative Chemopreventive Agent, in Colorectal Cancer Patients: Silibinin Levels in Plasma, Colorectum, and Liver and Their Pharmacodynamic Consequences

Silymarin and epithelial cancer chemoprevention: How close we are to bedside?

Design and Evaluation of a Novel Evodiamine-Phospholipid Complex for Improved Oral Bioavailability

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