The human fibroblast MRC-5 cells incubated with PHB granules (TM) added at a final concentration of 4 mg/ml showed a time-course pattern of survival. The percentages of dead cells obtained were at the rate of 3.8% after 7 days, respectively. When the MRC-5 cells grown in different material, using the test concentration of 4 mg/ml PCM, they were found to show a similar time-course increasing pattern of death as that obtained with PHB. However, the death was noted in the cells incubated for 7 days, the death rates obtained was 40.54% respectively.
Cell Line ; Cell Survival/*drug effects ; Fibroblasts/drug effects ; Hydroxybutyrates/*toxicity ; *Materials Testing ; Polymers/*toxicity

OBJECTIVE: This phase I study aimed to determine the maximum tolerated dose (MTD) of Genexol-PM, when combined with carboplatin, as a first-line treatment in patients with advanced ovarian cancer. METHODS: This open-label, multicenter, phase I, dose-escalation study included 18 patients (median age: 59.0 years, range: 40–75 years) diagnosed with advanced epithelial ovarian cancer. All patients had measurable residual disease after debulking surgery. Patients were assigned to groups (n=6 each group) that received different doses of Genexol-PM (220, 260, and 300 mg/m², once every 3 weeks) and 5 area under the curve (AUC) carboplatin. Safety and efficacy were analyzed for each dose group. RESULTS: In this intention-to-treat population, 3 out of 18 patients dropped out of the study: 1 due to dose-limiting toxicity (DLT), 1 due to hypersensitivity, and 1 was lost during follow-up. DLTs were not reported at 220 mg/m² or 260 mg/m², but at 300 mg/m², 1 patient experienced DLT (grade 3 general pain). The MTD of Genexol-PM was not determined, but a dose of 300 mg/m² or less could be recommended for the phase II study. Most patients (73.9%) with adverse events recovered without sequelae, and no death occurred that was related to the disease or treatment. The best overall response rate was 94.1%. CONCLUSION: Genexol-PM combined with carboplatin was well tolerated as a first-line treatment, and good responses were observed in patients with advanced ovarian cancer. Based on these results, we recommended a dose of 300 mg/m² or less for a phase II study.
Carboplatin* ; Follow-Up Studies ; Humans ; Hypersensitivity ; Maximum Tolerated Dose ; Ovarian Neoplasms* ; Paclitaxel* ; Polymers* ; Toxicity Tests

A novel multi-components microcapsule--SA/CS-CaCl2/PMCG system was introduced. The effects of PMCG and SA/CS-CaCl2/PMCG microcapsules on the growth of free E. coli and Saccharomyces cerevisiae were studied respectively. In addition, the growth of immobilized E. coli and Saccharomyces cerevisiae were also investigated. The results showed that: Just like other synthetic polycations, PMCG above certain concentration (0.5%) strongly inhibited the growth of free E. coli and Saccharomyces cerevisiae, but SA/CS-CaCl2/PMCG microcapsules almost had no effects on their growth and on the consumption of glucose concentration by Saccharomyces cerevisiae. What's more, immobilized E. coli and Saccharomyces cerevisiae grew almost as normally as free cultivation. As a whole, SA/CS-CaCl2/PMCG microcapsules had good biocompatiability and can be used as a new immobilization system.
Alginates ; toxicity ; Biocompatible Materials ; toxicity ; Calcium Chloride ; toxicity ; Cellulose ; analogs & derivatives ; toxicity ; Escherichia coli ; drug effects ; growth & development ; Glucuronic Acid ; Hexuronic Acids ; Polymers ; toxicity ; Saccharomyces cerevisiae ; drug effects ; growth & development

Hypersusceptibility test, pyrogen test, cell cultivation, and toxicity examination were applied in the biological evaluation of the poly(lactic acid) (PLA)/chitosan composite materials. The results indicated that all the materials were negative, conforming to the ISO10993-1. The cell could grow well on the surface of the materials. So the PLA/chitosan composite materials have good biocompatibility and can be planted in the body as scaffolds.
Animals ; Biocompatible Materials ; chemical synthesis ; toxicity ; Cell Adhesion ; drug effects ; physiology ; Cells, Cultured ; Chitin ; analogs & derivatives ; chemical synthesis ; toxicity ; Chitosan ; Female ; Guinea Pigs ; Lactic Acid ; chemical synthesis ; toxicity ; Male ; Materials Testing ; Polyesters ; Polymers ; chemical synthesis ; toxicity ; Rabbits

The authors, after inducing acute sinusitis in rabbits, compared cases where we opened the natural ostium and a general dose of administered antibiotics and cases where we opened the natural ostium and locally administered dose of antibiotics using polymer, and found that the application of local antibiotics using polymer is the superior of the two in treating sinusitis. To be able to develop a treatment for sinusitis using antibiotics incorporating polymer, we first need to examine the toxicity of polymer. The purpose of this study was to examine the toxicity of polymer through a general toxicity test as well as a special toxicity test in experiments using animals. As a result of this study, we discovered that poly-L-lactic acid (PLA) polymer works as an intraperitoneal foreign body and causes adhesion of viscera, but nethier acute nor subacute toxicity of PLA polymer was detected, and no negative effect on reproductive function was observed. It was also observed to induce neither immune reaction such as hypersensitivity nor local toxicity to the maxillary sinus mucosa of rabbit. We conclude that the results of this study can provide basic information for developing antibiotics-incorporating PLA polymer for the treatment of sinusitis and for clinical experiments involving such antibiotics.
Animals ; Anti-Bacterial Agents ; Foreign Bodies ; Hypersensitivity ; Maxillary Sinus ; Mucous Membrane ; Polymers* ; Rabbits ; Sinusitis* ; Toxicity Tests ; Viscera

OBJECTIVETo establish an animal model of lung injury in SD rats using intratracheal instillation of unknown polymer and to provide the base for exploring the molecular mechanism of lung tissue injury induced by occupational exposure.

METHODSOne hundred forty SD rats were randomly divided into seven groups, including the control group 1 which was exposed to normal solution, the control group 2 which was not exposed to any one and five treatment groups which were exposed to 1 ml unknown polymer (0.5 ml for each lung) at the doses of 40, 30, 20, 10 and 5 mg/ml, respectively by intratracheal instillation. The rats were sacrificed on the 1st, 3rd, 7th, 10th, 14th, 21th and 28th day after exposure, then the lung tissues were examined pathologically and the blood bio-chemical analysis was conducted.

RESULTSThe results of blood biochemical analysis indicated that ALT and AST levels in rats exposed to 30 and 40 mg/ml unknown polymer were significantly higher than those in control groups. Intratracheal instillation of unknown polymer can causes PLF in experimental animals on the 14th days after exposure. The results of pathological examination exhibited that the lung tissue injury in rats exposed to unknown polymer for 14 days or more was found and the dose-effect relationship was observed.

CONCLUSIONAn animal model of lung injury in SD rats induced by unknown polymer with intratracheal instillation was established successfully. The results of pathological examination showed that the types of rat lung injury were similar to the clinical lung injury after exposure to unknown polymer, which provided a base for studying the mechanism of lung injury caused by occupational exposure to unknown polymer.

Animals ; Disease Models, Animal ; Female ; Lung ; drug effects ; pathology ; Lung Injury ; chemically induced ; Male ; Polymers ; toxicity ; Rats ; Rats, Sprague-Dawley

This is a study on the biodegradable polymers as gene controlled-released coatings for gene transfer. The PELA (poly (Dl-lactic acid)-co-poly (ethylene glycol), and PLGAE (poly (lactic acid)-co-poly (ethylene glycol)-co-poly (glycolic acid) random copolymer) were synthesized and prepared as the coatings of plasmid pCH110 in the transfection. All kinds of factors affecting the loading efficiency, cytotoxicity, transfection efficiency and the course of the degradation and release in vitro were discussed. The average diameters of microspheres of PELA and PLGAE were 1-3 microm and 0.72 microm respectively. The loading efficiency levels of them were 62% and 70% respectively. The transfection efficiency levels of two kinds of pCH110 delivery system for COS-1 cells were higher and two of them had few cytotoxicity. After transfection, the X-gal assay was performed and reported positive for 96 h. The biodegradable polymeric materials as gene carriers possess their potential superiority.
Biocompatible Materials ; DNA ; chemistry ; Drug Carriers ; chemical synthesis ; chemistry ; toxicity ; Gene Transfer Techniques ; Lactates ; chemical synthesis ; chemistry ; toxicity ; Lactic Acid ; chemical synthesis ; chemistry ; toxicity ; Polyethylene Glycols ; chemical synthesis ; chemistry ; toxicity ; Polyglycolic Acid ; chemical synthesis ; chemistry ; toxicity ; Polymers ; chemical synthesis ; chemistry ; toxicity ; Transfection

For the purpose of increasing the hydrophilicity of poly aspartic acid, a series of polymer of L-aspartic acid and 4-aminobutanoic acid with different ratios (mol/mol) were prepared. The copolymers were characterized by 13CNMR, DSC and x-ray. The confirmed the structures of the polymers. In-vitro tests of release at phosphate buffer saline, enzyme solution of trypsin and papain (37.0 degrees C, pH = 7.4) were carried out. The result indicated that the polymers could be degraded in some degree, and that 4-aminobutanoic acid segments accelerated the degradation rate of the polymers. Skin irritation test and systemic acute toxicity test were carried out, which showed that the polymer was a nontoxic biomedical material.
Animals ; Aspartic Acid ; chemistry ; Female ; Hydrolysis ; Male ; Materials Testing ; Mice ; Polymers ; chemical synthesis ; chemistry ; metabolism ; toxicity ; Rabbits ; gamma-Aminobutyric Acid ; chemistry

OBJECTIVETo investigate the effect of tea polyphenols on cell apoptosis in rat model of cyclosporine-induced chronic nephrotoxicity.

METHODSFour groups of animals in rat model of cyclosporine-induced chronic nephrotoxicity were respectively treated by olive oil (n = 6), tea polyphenols (TP, n = 6), cyclosporine A (CsA, n = 8) and TP plus CsA (n = 8). At the end of 28th day of treatment, all animals were sacrificed and blood was analyzed for blood serum creatinine and creatinine clearance, kidney tissue for pathologic analysis. The TUNEL assay, caspase-3 mRNA expression detected by reverse transcription-polymerase chain reaction (RT-PCR) and caspase-3 activity were used for the analysis of cell apoptosis.

RESULTSCsA plus TP ameliorated the CsA-induced decrease of renal function and interstitial fibrosis. There was a significant increase in the number of apoptosis-positive cells in the CsA-vs-CsA plus TP-treated group at four weeks (18.9 +/- 3.3 vs. 7.7 +/- 1.4, P < 0.05). The expression of caspase-3 mRNA and caspase-3 activity of CsA-treated group was significantly higher than that of CsA plus TP-treated group (P < 0.05).

CONCLUSIONThese results indicate that antioxidant tea polyphenols significantly inhibit apoptosis of tubular and interstitial cells in rat model of chronic cyclosporine-induced nephrotoxicity, and suggest that the decrease of cell apoptosis exerted by tea polyphenols may be one of mechanisms to protect renal function and tissue structure.

Animals ; Antioxidants ; pharmacology ; Apoptosis ; drug effects ; Caspase 3 ; Caspases ; genetics ; Cyclosporine ; toxicity ; Flavonoids ; Immunosuppressive Agents ; toxicity ; In Situ Nick-End Labeling ; Kidney ; drug effects ; Male ; Phenols ; pharmacology ; Polymers ; pharmacology ; Polyphenols ; RNA, Messenger ; analysis ; Rats ; Rats, Sprague-Dawley ; Tea

Chitosan and its derivatives are extensively studied as non-viral gene delivery vectors nowadays. Polyethylene glycol-chitosan (mPEG-CS) copolymers were synthesized by oxidation of mPEG-OH and then combined mPEG-CHO with amino groups on chitosan chains. The in vitro cytotoxicity of copolymers was evaluated by MTT method. The results showed > 70% cell viability of HeLa and A549 cells after incubation with mPEG-CS copolymer from concentration 5 to 100 microg x mL(-1). The mPEG-CS copolymers with various degrees of PEG substitution were combined with DNA and the properties of mPEG-CS/DNA complexes were investigated such as nanoparticle size, zeta potential and agarose gel analysis. The best one among all these mPEG-CS copolymers was mPEG (3.55) -CS, for its capability to condense plasmid DNA was most efficient. For this reason, mPEG (3.55) -CS was picked out to mediate plasmid enhanced green fluorescence protein (pEGFP) and transfect HeLa and A549 cells. The expression of green fluorescence protein was observed by fluorescence microscope and the transfection efficiency was detected by flow cytometry. The gene expression mediated by mPEG-CS was resistant to serum, and the optimal transfection efficiency (8.1% for HeLa cells and 4.8% for A549 cells) of mPEG-CS/EGFP system was obtained under the condition of N/P 40 and 48 h transfection time. These results indicate that mPEG-CS copolymer is an efficient non-viral gene vector.
Adenocarcinoma ; pathology ; Cell Line, Tumor ; Chitosan ; chemistry ; toxicity ; Drug Carriers ; Genetic Vectors ; chemistry ; HeLa Cells ; Humans ; Lung Neoplasms ; pathology ; Nanoparticles ; Particle Size ; Plasmids ; Polyethylene Glycols ; chemistry ; toxicity ; Polymers ; Transfection