Methoxypolyethylene glycol-poly lactic acid (PELA) was synthesized by ring-opening copolymerization of lactide in the presence of mPEG and its structure was characterized by 1H NMR. The novel hypomicrons were prepared by solution-casting method using PELA block copolymer as a matrix and 7-ethyl-10-hydroxycamptothecin (SN-38) as an antitumor agent. The morphology, size and size distribution, drug loading, entrapment efficiency, and release characteristics in vitro of the SN-38 loaded hypomicrons were studied. The results showed that the obtained hypomicrons showed spherical shape with the core-shell structure, the sizes are in the range of 157-238 nm, and the drug loading content varied from 1.35%-3.58% depending on the copolymer composition and the SN-38 fed amount. The in vitro release behavior in phosphate-buffered saline, pH 7.4, exhibited a sustaining release manner and was affected by the copolymer composition. The drug-loaded amount and entrapment efficiency decreased with increasing the molecular weight of the copolymer. With the increasing of the SN-38 fed amount, the drug-loaded amount and the size of hypomicrons increased, the entrapment efficiency decreased. The SN-38 hypomicrons increased the solubility of SN-38 in water and were valuable for the development of the novel dosage form of SN-38.
Antineoplastic Agents, Phytogenic ; administration & dosage ; Camptothecin ; administration & dosage ; analogs & derivatives ; Drug Carriers ; Lactic Acid ; chemistry ; Microspheres ; Particle Size ; Polyesters ; Polyethylene Glycols ; chemistry ; Polymers ; chemistry ; Solubility ; Technology, Pharmaceutical

AIMTo investigate the intestinal absorption of silybin (SLB) in male rats.

METHODSSingle-pass intestinal perfusion (SPIP) technique was performed in each isolated region of the small intestine at a flow rate of 0.1 mL x min(-1). The samples of perfusate and portal plasma were collected at the designated periods of time after rat intestinal perfusion and analyzed for drug by HPLC.

RESULTSThe absorption rate constant (k(a)) and the effective permeability (P(eff)) of SLB at 190 microg x mL(-1) were determined for each segment. These data indicated the absorption rate were duodenum > jejunum > ileum > colon. SPIP was also performed in duodenum with three concentrations of SLB (80, 190 and 300 microg x mL(-1)). The concentration dependent changes of k(a) and P(eff) were evident in the duodenum perfusion of silybin. At silybin perfusate concentrations of 80 microg x mL(-1), k(a) and P(eff) were different from the values at either of the two higher concentrations (190 and 300 microg x mL(-1), P < 0.05). However there was no difference between 190 microg x mL(-1) and 300 microg x mL(-1) groups. The drug mass appearing in the plasma further indicated the absorption were duodenum > jejunum > ileum > colon.

CONCLUSIONSLB can be absorbed in whole intestinal sections. When the concentration raises to a certain level, the uptake of SLB will not increase.

Animals ; Colon ; metabolism ; Duodenum ; metabolism ; Ileum ; metabolism ; Intestinal Absorption ; Intestine, Small ; metabolism ; Jejunum ; metabolism ; Male ; Milk Thistle ; chemistry ; Perfusion ; Plants, Medicinal ; chemistry ; Rats ; Rats, Sprague-Dawley ; Silymarin ; blood ; isolation & purification ; pharmacokinetics

In order to study the intestinal absorption behaviors of three active constituents, columbianetin acetate, osthole and columbianadin in Radix Angelicae Pubescentis extracts, in situ rat single pass intestine perfusion (SPIP) was carried out by the perfusion solution of the extract I containing less than 10% total coumarins. The absorption of extract II containing more than 60% total coumarins was compared with that of extract I by rat colon SPIP to elucidate the influence on absorption of the different coumarin content extracts of the Chinese traditional medicine. The samples of the perfusion solution were collected in certain intervals. The concentrations of three active components in the perfusion samples were determined by HPLC method. The results demonstrated that the absorption rate constants (Ka) or apparent permeability coefficients (Papp) of columbianetin acetate, osthole and columbianadin from extract I had no significant difference among concentration ranges of 62-555 microg x mL(-1), 101-887 microg x mL(-1), 19-186 microg x mL(-1), respectively. The absorption quantity of three components was proportional to its concentration respectively and the saturate absorption phenomena were not observed. This suggested that the absorption of columbianetin acetate, osthole and columbianadin showed the passive diffusion process. Three components could be absorbed in whole intestinal sections. The Ka and Papp of three components all showed colon > duodenum > jejunum > ileum in four different regions of rat intestine. At colon, Ka and P app were significant different from the others. The Ka or Papp of three components from the extract I was significantly more than that of same components from extract II. The extract I redounded to increase the absorption of three active components.
Angelica ; chemistry ; Animals ; Chromatography, High Pressure Liquid ; methods ; Colon ; metabolism ; Coumarins ; isolation & purification ; pharmacokinetics ; Drugs, Chinese Herbal ; isolation & purification ; pharmacokinetics ; Duodenum ; metabolism ; Furocoumarins ; isolation & purification ; pharmacokinetics ; Ileum ; metabolism ; Intestinal Absorption ; Jejunum ; metabolism ; Male ; Perfusion ; Plant Roots ; chemistry ; Plants, Medicinal ; chemistry ; Rats ; Rats, Sprague-Dawley

AIMTo study the non-ion surfactant vehicle (niosome) entrapped-camptothecin.

METHODSThe niosome loaded with camptothecin was prepared from Span and cholesterol using aqueous dispersion of film. The vehicles were visualised by transmission electron microscopy and sized by laser particle analyzer on a Malvern Mastersizer. An HPLC analysis method of the camptothecin was established by fluorescence detection. The entrapment efficiency of the niosomes containing camptothecin was determinated after the ultracentrifugation of the niosome. The antitumor activities of the vehicles on S180 sarcoma in mouse were studied.

RESULTSThe given niosomes were the suspension finely dispersed in aqueous solution. They were spherical vehicles with the single lamellar bilayers similar to phospholipid vehicles. The mean sizes of the vehicles were (565 +/- 6) nm. The recovery of the HPLC analysis method was 100.3% with 0.4% RSD. The entrapment efficiency of the camptothecin encapsulated by the niosome was 61%. The inhibition (%) of the niosome loaded with camptothecin on S180 sarcoma in mouse were 76.1% (P < 0.05). After the given dose the weight of the mouse of the niosome groups were 92.7% (P > 0.05) and 134.7% of blank control groups and compatothecin solution groups, respectively.

CONCLUSIONThe camptothecin niosomes were spherical in shape and similar to phospholipid vehicles with singlelamellar bilayers. Their size distributions were narrow. Their entrapment efficiency were higher. Its antitumor activity was better than camptothecin.

Acrylic Resins ; chemistry ; Animals ; Antineoplastic Agents, Phytogenic ; administration & dosage ; therapeutic use ; Camptothecin ; administration & dosage ; therapeutic use ; Cholesterol ; chemistry ; Disease Models, Animal ; Drug Compounding ; Drug Delivery Systems ; Mice ; Neoplasm Transplantation ; Particle Size ; Sarcoma 180 ; drug therapy ; pathology ; Surface-Active Agents ; Tumor Cells, Cultured

To synthetize 3-carboxypropyl-triphenylphosponium bromide-polycaprolacton-CTPP-PEG-PC, and prepare curcumin CTPP-PEG-PCL micelles by using the self-assembled emulsion solvent evaporation method, in order to determine the critical micelle concentration (CMC) with the pyrene fluorescent probe technology, detect the particle size, entrapment efficiency (%), morpheme and in vitro release rate, and evaluate the cytotoxicity of hepatic stellate cells with MTT assay. The structure of CTPP-PEG-PCL had been identified by 1H-NMR spectra. Specifically, the CMC of polymer was 2.25 mg x L(-1), the average size was 190 nm, the drug content was (0.66 +/- 0.008) g x L(-1), and the entrapment efficiency was (94 +/- 0.6)%. The in vitro release results showed curcumin micelles had a significant higher inhibition ratio in the growth of hepatic stellate cells than crude curcumin (P < 0.05). This suggested that CTPP-PEG-PCL micelles feature low CMC, high encapsulation efficiency and notable inhibition effect in growth of hepatic stellate cells.
Cell Line ; Cell Proliferation ; drug effects ; Curcumin ; administration & dosage ; chemistry ; pharmacology ; Hepatic Stellate Cells ; drug effects ; Micelles ; Polyesters ; administration & dosage ; chemistry ; Polyethylene Glycols ; administration & dosage ; chemistry

OBJECTIVETo observe the influence of endoscopic radial artery harvesting techniques on the prevalence of complications after coronary artery bypass grafting, and to assess the potential trauma to the radial artery through the histological changes.

METHODSFrom August 2003 to June 2008, 87 patients undergoing CABG had radial artery harvested by endoscopic harvesting system. About 4 mm proximal and distal radial artery end segment of 10 patients undergoing endoscopic and conventional harvesting were examined with light and electro-microscope.

RESULTSThe endoscopic harvest time was 42 to 98 min, with a mean of (57.6 +/- 17.3) min. The harvested conduit length was 15 to 20 cm, with a mean of (17.5 +/- 1.6) cm. Objective dorsal thenar numbness remained in 7 patients, none complained of forearm numbness at 3-month follow-up. The result of light and electro-microscope had no differences in the intima, media, or adventitia between endoscopically and conventionally obtained radial artery segments.

CONCLUSIONThe use of endoscopic radial artery harvesting in coronary artery bypass grafting can be performed safely with infrequent complications. This method results in excellent patient satisfaction, particularly regarding the cosmetic outcome.

Adult ; Aged ; Coronary Artery Bypass ; Endoscopy ; Female ; Humans ; Male ; Middle Aged ; Radial Artery ; transplantation ; Tissue and Organ Harvesting ; methods ; Treatment Outcome