This study aimed to prepare andrographolide (AP)-loaded glycyrrhizic acid (GA) micelles (AP-GA)-PMs to enhance the solubility and anti-tumor effect of andrographolide. Firstly, andrographolide (AP) was used as the model drug and glycyrrhizic acid (GA) as carriers to prepare (AP-GA)-PMs. Then the preparation methods and the ratios of drug and carrier were screened and optimized based on particle size, encapsulation efficiency (EE) and loading capacity of micelles. Finally, the pharmaceutical characters and the inhibition rate on HepG2 cells were evaluated on the (AP-GA)-PMs prepared by optimal process. The results showed that the prepared micelles under the optimal process had a nanosize of (127.11±1.38) nm, zeta potential of (-24.01±0.55) mV, the entrapment efficiency rate of (92.01±4.02)% , the drug loading rate of (51.44±1.24)% and high storage stability at 4 °C in 30 d, with slow but highly stable release. Moreover, (AP-GA)-PMs with the IC₅₀ value of 19.25 mg·L⁻¹ had a more synergistic and better anti-tumor effect in comparison with AP (IC₅₀=122.40 mg·L⁻¹) on HepG2 cells (P<0.01). In conclusion, the (AP-GA)-PMs prepared with glycyrrhizic acid as a carrier had a small particle size, large drug loading capacity, and high stability, and could significantly improve the anti-tumor effects of AP.
Antineoplastic Agents ; pharmacology ; Diterpenes ; pharmacology ; Drug Carriers ; chemistry ; Glycyrrhizic Acid ; chemistry ; Micelles ; Particle Size ; Polymers

OBJECTIVETo prepare a platinum microcoil coated with polymers and vascular endothelial growth factor (VEGF), and evaluate its surface characteristics and property of sustained VEGF release.

METHODSThe surface of the platinum microcoils (GDC) were modified by coating P(DLLA-co-TMC) copolymer and immobilizing heparin on the surface of GDC. VEGF was then loaded onto the surface of GDC and the controlled release of VEGF within GDC was achieved. The morphology was observed by scanning electron microscope, and the sustained release of VEGF was evaluated by enzyme-linked immunosorbent assay (ELISA).

RESULTSPlatinum coils were prepared by successive deposition of P(DLLA-co-TMC) copolymer and anionic heparin, and VEGF was immobilized through affinity interaction with heparin. The accumulative release of VEGF increased obviously during the entire testing period without burst release.

CONCLUSIONThe use of P(DLLA-co-TMC) copolymer allows immobilization of VEGF on the platinum coils for controlled VEGF release, and improves the biological property of the coils.

Coated Materials, Biocompatible ; chemistry ; Delayed-Action Preparations ; pharmacology ; Platinum ; chemistry ; Polymers ; chemistry ; Vascular Endothelial Growth Factor A ; pharmacology

N-acetyl-L-cysteine (NAC) capped quantum dots (QDs) were synthesized by a hydrothermal method and coated with 2-amino-2-deoxy-D-glucose (DG), polyethylene glycol (PEG), and 9-D-arginine (9R). The optical properties, morphology and structure of 9R/DG-coated CdTe QDs were characterized by ultraviolet-visible spectrometry, fluorescence spectrum, Fourier transform infrared (FTIR), proton nuclear magnetic resonance (1H NMR), liquid chromatography-mass spectrometer (LC-MS), sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and transmission electron micrographs (TEM). Furthermore, the biocompatibility, tumor targeted ability and transmembrane action of 9R/DG-coated CdTe QDs were studied. Results indicated that 9R/DG-coated CdTe QDs was constructed successfully by ligand exchange. The 9R/DG-coated CdTe QDs with the size of 8-10 nm had good dispersity and the absorbance and fluorescence peaks of CdTe QDs after modification were red shifted from 480 nm to 510 nm and 627 nm to 659 nm, respectively. In addition, the CdTe QDs modified by PEG, DG and 9R displayed good biocompatibility, high targeted ability to the cancer cells with glucose transporter type 1 (GLUT1) receptor high expression and obvious transmembrane ability.
Acetylcysteine ; chemistry ; Cadmium Compounds ; pharmacology ; Humans ; Neoplasms ; drug therapy ; Polymers ; chemistry ; Quantum Dots ; chemistry ; Spectrophotometry, Ultraviolet ; Tellurium ; pharmacology

OBJECTIVE: To determine the feasibility whether the bovine jugular venous conduit (BJVC) can be fixed with polyepoxy compound (PC). METHODS: Twenty-four BJVCs were divided into 3 groups and fixed with polyepoxy compound (PC group, n = 8), glutaraldehyde (GA group, n = 8), and unfixed group (Control group, n = 8), respectively. The morphologic and mechanical properties of BJVCs in the 3 groups, including thickness, diameter, moisture content, denaturation temperature, tensile strength, elongation at break, and fixation index were measured. The rat subcutaneous model for the assessment of tissue calcification was used. The calcium content in bovine jugular vein patches and valves was determined by flame atomic absorption spectrophotometer. RESULTS: There was no difference in the wall thickness, diameter, and tissue water content between PC and the control group, but significant difference was found between GA and PC groups. The mechanical properties of PC group and GA group were not significantly different, but they were better than those of the control group. GA-fixed BJVC samples showed clear calcification, while PC fixed BJVC were calcified significantly less. CONCLUSION PC is an effective and suitable choice for the treatment of BJVC since it can effectively preserve the structure and the anti-reflow function of valves in bovine jugular vein and it has better anti-calcification properties.
Animals ; Biocompatible Materials ; Bioprosthesis ; Blood Vessel Prosthesis ; Cattle ; Cross-Linking Reagents ; pharmacology ; Epoxy Compounds ; pharmacology ; Jugular Veins ; Polymers

OBJECTIVETo develop a drug delivery system triptolide-polyethylenimine-cyclodextrin and to evaluate its anticancer activity in vitro.

METHODSTriptolide was conjugated to polyethylenimine-cyclodextrin by N, N'-carbonyldiimidazole to form triptolide-polyethylenimine-cyclodextrin. (1)H-NMR, FT-IR and XRD were used to confirm its structure. The anticancer effect of the polymer was assessed by MTT assay, erasion trace test and hematoxylin-eosin staining. The potential to condense siRNA and to delivery siRNA into cytoplasm was demonstrated by gel retardation assay, zeta-potential determination and fluorescence staining.

RESULTSTriptolide was successfully conjugated to polyethylenimine-cyclodextrin and the conjugation rate of triptolide was 10% (w/w). siRNA was effectively condensed by the polymer at the N/P ratio of 5, and its particle size was 300 ±15 nm and zeta potential was 8 ±2.5 mV. MTT assay, erasion trace test and hematoxylin-eosin staining revealed that triptolide-polyethylenimine-cyclodextrin had anticancer effect and low cytotoxicity to normal cells. The polymer was able to deliver siRNA to the cytoplasm effectively as demonstrated by fluorescence staining.

CONCLUSIONTriptolide-polyethylenimine-cyclodextrin is able to inhibit the growth and migration of cancer cells in vitro and to carry siRNA into cells effectively. It is potential to be used as a novel prodrug for co-delivery of gene and drug in cancer treatment.

Antineoplastic Agents ; administration & dosage ; pharmacology ; Cell Line, Tumor ; Cyclodextrins ; Diterpenes ; administration & dosage ; pharmacology ; Drug Carriers ; Epoxy Compounds ; administration & dosage ; pharmacology ; Humans ; Nanoparticles ; Phenanthrenes ; administration & dosage ; pharmacology ; Polyethyleneimine ; Polymers

OBJECTIVETo prepare cisPLLAtin-loaded polylactic acid/cnts, and to study the anti-tumor effect of 5-FU-PLLA-CNTs on human gastric carcinoma cell lines(MGC803 and MNK45).

METHODS5-FU-PLLA-CNTs were prepared with ultrasound emulsification. The morphology of 5-FU-PLLA-CNTs was determined by scanning electron microscope(SEM), and its drug loading and drug release curve in vitro were detected by UV-Vis-NIR spectrophotometer. Cells were divided into experiment, positive control and negative control groups. CCK8 method was used to test the cytotoxic effect of 5-FU-PLLA-CNTs in different concentrations on MGC803 and MNK45 cell proliferation. Flow cytometry was employed to measure the apoptotic rate of MGC803 and MNK45 cells before and after the intervention of 5-FU-PLLA-CNTs.

RESULTSDeep layer film of 5-FU-PLLA-CNTs was successfully established, whose drug-load rate was(4.54±0.43)%, entrapment rate was(21.56±2.36)%. In vitro release test showed release rate within 24 h of 5-FU-PLLA-CNTs was 23.9% in a as lowly increasing manner, and accumulating release rate was 85.3% at day 31. CCk8 experiment revealed, as compared to control group, 5-FU-PLLA-CNTs significantly inhibited the proliferation of two cell lines in dose-dependent and time-dependent manner. The best 5-FU-PLLA-CNTs concentration of inhibition for human gastric cancer cell lines was 1 mg/well. Flow cytometry indicated the apoptotic rate of MGC803 and MNK45 cells in experiment group treated by 1 mg/well 5-FU-PLLA-CNTs significantly increased as compared to negative control group (P<0.05), while the difference was not significant as compared to positive control group (P>0.05).

CONCLUSIONThe 5-FU-PLLA-CNTs has good drug sustained-release capacity, and can significantly kill and inhibit the proliferation of MGC803 and MNK45 cell lines.

Cell Line, Tumor ; Cell Proliferation ; drug effects ; Delayed-Action Preparations ; Fluorouracil ; pharmacology ; Humans ; Lactic Acid ; pharmacology ; Nanotubes, Carbon ; Polyesters ; Polymers ; pharmacology ; Stomach Neoplasms ; pathology

Lamellar particles(lamellae) were prepared by non-solvent precipitation from crystalic poly-L-lactic acid (PLLA). The PLLA lamellae exhibite a diamond or stepped irregular shape with a size range between 3-5 microns. Prepared without any surfactants and dispersing agents, the lamellar particles have clean surface, which is advantageous for the adsorption of proteins. The PLLA lamellar particles adsorbed protein cytokine interferon-alpha (IFN-alpha) with an adsorption efficiency of > or = 95%. The release of loaded IFN could continue for more than 10 days. The cell incubation experiments showed that the PLLA lamellar particles were easy to be phagocytosed by macrophages. The immunological experiments showed that the biological activity of IFN-alpha loaded on the PLLA lamellar particle was effectively retained.
Adsorption ; Chemistry, Pharmaceutical ; Drug Carriers ; Interferon-alpha ; chemistry ; pharmacology ; Lactic Acid ; chemistry ; Particle Size ; Polyesters ; Polymers ; chemistry

OBJECTIVETo study the ectopic osteogenesis of tissue engineered bone with recombinant human bone morphogenetic protein/transforming growth factor-beta (rhBMP/TGF-beta) or WO-1 slow-released factors.

METHODSPartial demineralized freeze-dried bone (PDFDB) of pig was used as scaffold material. rhBMP/TGF-beta or WO-1 were pre-coated on the surface of material by means of vacuum negative pressure absorption, and then coated with polylactic acid (PLA) to make slow-released material. There were six group: PDFDB material (group A); PDFDB combined with osteoblasts (group B); PDFDB material with rhBMP/TGF-beta slow-released system (group C); PDFDB material combined with rhBMP/TGF-beta slow-released system osteoblasts (group D); PDFDB with WO-1 slow-released system (group E); PDFDB material combined with WO-1 slow-released system and osteoblasts (group F) were implanted in bilateral lower limbs of 36 Newzealand rabbits respectively (6 rabbits in each groups). Histological, histochemical and biochemical analysis were detected 2, 4, 6, 8 weeks after operation.

RESULTSWithin the observation periods, no osteogenesis was observed in group A. The osteogenesis in group B, D, F were superior to that of group C and E (P < 0.05). The osteogenetic activity in group C and E was delayed. The quantity and quality of osteogenesis in group D and F were 2 weeks ahead of time compared with group B, and 4 weeks to that of group C and E. The newborn calcification content was superior to that of group A, C, and E (P < 0.05).

CONCLUSIONSThe osteogenesis of PDFDB materials with BMP/TGF-beta or WO-1 is slower than that of which combined with osteoblasts. Simple material PDFDB has no ectopic osteogenesis.

Animals ; Bone Morphogenetic Proteins ; pharmacology ; Bone Substitutes ; pharmacology ; Child ; Drug Synergism ; Female ; Humans ; Lactic Acid ; pharmacology ; Osteogenesis ; drug effects ; Polyesters ; Polymers ; pharmacology ; Rabbits ; Recombinant Proteins ; pharmacology ; Swine ; Tissue Engineering ; Transforming Growth Factor beta ; pharmacology

OBJECTIVETo determine the efficacy of polylactic acid glue in preventing epidural scar adhesion after laminectomy in rabbits.

METHODSTwenty-four Japanese white rabbits underwent laminectomy (including the attached ligaments) at L(2 ) and L(5). After laminectomy at L(5), polylactic acid glue was sprayed on the dura and nerve roots and this segment was taken as the experimental group. After laminectomy at L(2), nothing was used and this segment was enrolled as the self control group. Four rabbits were killed every two weeks postoperatively till the end of the experiment at 12 weeks. Then the operated spine was observed grossly, histologically and ultrastructurally to check the degree of scar formation, the status of epidural scar adhesion, the absorption of the glue, and the intracellular structure of fibroblasts.

RESULTSThe glue coagulated immediately after spraying and showed excellent hemostatic effect. The glue membrane was easy to be taken away from the dura mater of the samples for 2 weeks and there were no cells in the epidural space in the experimental group. But the dura mater was covered by hematoma in the control group, which formed mild adhesion, with fibroblasts proliferating actively. In the 4th week, some glue shivers remained in the epidural space with fibroblasts increasing a little, and the dura mater was smooth in the experimental group. However, in the control group, the formed scar was fragile and conglutinated with the dura mater diffusely and fibroblasts were much more than those in the experimental group. In the 6th-12th weeks, there was a potential interspace between the scar and the dura mater, and the polylactic acid glue was absorbed completely in the experimental group. Much tough scar was found in the control group, which was very difficult to dissect from the dura mater and the surrounding tissues. From the ultrastructural observation of the fibroblasts, the nucleus became much bigger and the rough endoplasmic reticulum was much more plentiful in the control group than that in the experimental group.

CONCLUSIONSPolylactic acid glue can effectively reduce epidural cicatrization and adhesion.

Animals ; Biocompatible Materials ; Cicatrix ; prevention & control ; Lactic Acid ; administration & dosage ; pharmacology ; Laminectomy ; Membranes, Artificial ; Polyesters ; Polymers ; administration & dosage ; pharmacology ; Postoperative Complications ; prevention & control ; Rabbits ; Tissue Adhesions ; prevention & control

OBJECTIVETo overcome the deficiency in the current therapies for erectile dysfunction (ED), we designed and synthesized a novel high-efficiency polymer/gene compound drug controlled release system and discussed the feasibility of pH and temperature dually sensitive injectable hydrogel in ED gene therapy.

METHODSWe synthesized optimal siRNA gene nanoparticles by characterizing the zeta potential of polylysine (PLL)/siRNA gene compounds, and established a pH and temperature dually sensitive injectable gene compound drug controlled release system via Schiffs reaction between glycol chitosan (GC) and benzaldehyde capped OHC-PEO-PPO-PEO-CHO. Then we demonstrated the sustained release of the system at different temperatures.

RESULTSWhen the mass ratio of PLL to siRNA was 20:1, the zeta potential of the PLL/siRNA gene compound reached the peak (+23.5 mV) and the siRNA was encapsulated by PLL in the maximal degree. GC and OHC-PEO-PPO-PEO-CHO was crosslinked via benzoicimine reaction when environmental pH was changed from 5.5 to 7.4. The reslease of the siRNA encapsulated in this system kept at a low rate at 37 degrees C, significantly enhanced with the increase of the temperature to 60 degrees C, rising to (122.5 +/- 5.3) microg at 1 000 minutes as compared with (23.8 +/- 6.0) microg at 37 degrees C (P < 0.05).

CONCLUSIONThe polymer/gene compound drug controlled release system was successfully synthesized, which improved the stability and capacity of gene carriers and achieved siRNA release at different temperatures, promising to be a new approach to the gene therapy of ED.

Delayed-Action Preparations ; pharmacology ; Drug Delivery Systems ; Erectile Dysfunction ; drug therapy ; Genetic Therapy ; Humans ; Male ; Nanoparticles ; chemistry ; Polylysine ; chemistry ; Polymers ; RNA, Small Interfering ; pharmacology