AIM:To study the oral bioavailability of Silymarin-loaded Nanoparticles(SM-NP). METHODS: Beagle dogs were employed as experiment animals,Yiganling Tablet and Silymarin Extraction were used as the reference preparations.Three constituents were isolated on Ultimate~(TM) AQ-C_(18) column with mobile phase methanol:water(50∶50) at 0.8 mL/min flow rate using gradient elution and ESI ionic source and negative ion detection.Silybin plasma concentration in rat was determined by LC-M. RESULTS: The pharmacokinetics of the tested preparation and Yiganling Tablet met with one-compartment model.The relative bioavailability of three components of SMNP were higher than that of Yiganling Tablet. CONCLUSION: The results indicate that SM-NP has better bioavailability than the reference preparation,which confirms that nanoparticles is a good carrier for improving oral bioavailability of poorly-soluble drugs.

OBJECTIVETo study the absorption kinetics of dehydrocavidine in rats' stomachs and intestines.

METHODThe absorption kinetics was investigated by the in situ perfusion in rats and the concentrations of drug perfusion solutions were determined by HPLC.

RESULTThe hourly absorption percentages of dehydrocavidine in stomach, small intestine were 8.88%, 2.08%, respectively. Although the absorption rate constants of dehydrocavidine in duodenum and jejunum are more than that in ileum and colon, there is no significance difference between them. The absorption rate constants kept at the same level when the concentrations of drug perfusion solution are at middle and high level. The increase of the pH of perfusion solution didnt significantly affect the absorption rate constants of the drug.

CONCLUSIONDehydrocavidine was absorbed poorly at stomach and all segments of intestine in rats, but the absorptions in stomach are better than intestine. Dehydrocavidine was absorbed mainly via passive transport mechanism between middle and high concentration levels.

Animals ; Berberine Alkaloids ; pharmacokinetics ; Colon ; metabolism ; Duodenum ; metabolism ; Hydrogen-Ion Concentration ; Ileum ; metabolism ; Intestines ; metabolism ; Jejunum ; metabolism ; Male ; Rats ; Rats, Sprague-Dawley ; Stomach ; metabolism

Up to 70% of patients with late-stage breast cancer have bone metastasis. Current treatment regimens for breast cancer bone metastasis are palliative with no therapeutic cure. Disseminated tumor cells (DTCs) colonize inside the osteogenic niches in the early stage of bone metastasis. Drug delivery into osteogenic niches to inhibit DTC colonization can prevent bone metastasis from entering its late stage and therefore cure bone metastasis. Here, we constructed a 50% DSS6 peptide conjugated nanoparticle to target the osteogenic niche. The osteogenic niche was always located at the endosteum with immature hydroxyapatite. Arsenic-manganese nanocrystals (around 14 nm) were loaded in osteogenic niche-targeted PEG-PLGA nanoparticles with an acidic environment-triggered arsenic release. Arsenic formulations greatly reduced 4T1 cell adhesion to mesenchymal stem cells (MSCs)/preosteoblasts (pre-OBs) and osteogenic differentiation of osteoblastic cells. Arsenic formulations also prevented tumor cell colonization and dormancy via altering the direct interaction between 4T1 cells and MSCs/pre-OBs. The chemotactic migration of 4T1 cells toward osteogenic cells was blocked by arsenic in mimic 3D osteogenic niche. Systemic administration of osteogenic niche-targeted arsenic nanoparticles significantly extended the survival of mice with 4T1 syngeneic bone metastasis. Our findings provide an effective approach for osteogenic niche-specific drug delivery and suggest that bone metastasis can be effectively inhibited by blockage of tumor cell colonization in the bone microenvironment.