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Objective To modify polyethyleneimine (PEI) by using Poloxamer 188 (P188) , and evaluate its related feature as carriers of genes in vitro. Methods PEI was modified through conjugating one hydroxyl group of P188 to the amino group of PEI by carbonate method. Structural analysis of synthesized polymer was performed by using 1H-NMR. The particle size and Zeta potential of synthesized polymer /DNA complexes were measured. The cytotoxicity of the complexes was evaluated using MTT method in MCF-7 cells, HeLa cells and HepG2 cells. The pGL3-lus was used as a reporter gene, and the transfection efficiency of complexesat HeLa cells was evalutated by measuring activity of luciferase. Results The result of 1H-NMR showed the purity of these synthesized polymers was high. The particle size of complexes were decreased with the increment of N /P ratios. The Zeta potential of complexes increased with the increment of N /P ratios. The cytotoxicity of the complexes increased with the increment of N /P ratios. The synthesized polymers showed lower cytotoxicity than unmodified PEI. The new synthesized polymers had maintained the high transfection efficiency at high N /P ratios. In particular, the optimal transfection efficiency of (P188) 1- PEI (N /P = 24) was significantly higher than that of PEI (N /P = 6) . Conclusion The P188 modifed PEI can serve as a effective non-viral gene carriers to transfect Hela cells.
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Objective:To establish a paclitaxel (PTX)-resistance cell line of human cervical carcinoma Hela/PTX and investigate its biological features. Methods:Using Hela as the negative cells,drug-resistant cervical cancer Hela/PTX cells were applied as the target cells. The morphology changes were observed under an optical microscope;the drug resistance of Hela/PTX to different chemotherapeutic drugs was detected by CCK-8 method. The accumulation of drugs in the cells was determined by HPLC. The expression of P-glycoprotein (P-gp), Survivin protein and mRNA was detected by Western blot and RT-PCR. Results:Hela/PTX multidrug resistant cell line was successfully established. The resistance index to PTX was 58.40 and the resistance index of cross-resistance to docetaxel and 5-fluorouracil was 8.11 and 4.62,respectively. The mRNA expression level of P-gp and Survivin protein in Hela/PTX cells respectively was(9.93 +0.90) times(P < 0.05) and(3.02 +0.57) times(P <0.05) of that in Hela cells. The expression of P-gp and Survivin protein in drug-resistant cells was significantly higher than that in parental cells.Conclusion:Human cervical cancer resistant cell line Hela/PTX with the basic biological characteristics of multidrug resistance is successfully established, which can be used as an in vitro model for the studies on paclitaxel resistance mechanism and provide experimental basis for the studies of multidrug resistance mechanism of cervical cancer.
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OBJECTIVE:To improve the synthesis technology of 7-methoxy-4-(2-methyl-4-quinazolinyl)-3,4-dihydroquinoxalin-2 (1H)-ketone. METHODS:Using 2-methyl-4(3H)-quinazolone as starting material,the synthesis technology of 7-methoxy-4-(2-methyl-4-quinazolinyl)-3,4-dihydroquinoxalin-2(1H)-ketone was improved by clorination, nucleophilic substitution, diarylamine alkylation and nitro reductive cyclization. The yield of it was investigated. RESULTS:The structure of 7-methoxy-4-(2-methyl-4-quinazolinyl)-3,4-dihydroquinoxalin-2(1H)-ketone had been verified by 1H-NMR and ESI-MS. The yield was 43.5%and improved by 23.3% compared to 20.2% before improvement. CONCLUSIONS:Improved technology is simpler and milder, which is suitable for the batch preparation of laboratory study.
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Objective:To explore the effect of oxycontin combined with gabapentin on the clinical cure and immunity for patients with neuropathic cancer pain.Methods:80 patients with neuropathic cancer pain were enrolled in our hospital from June to 2016 July,of which patients divided into two groups randomly,Group A(n=40) accepted oxycontin treatment,and Group B (n=40) adopted gabapentin based on the patients in Group A.The VAS score and curative effect of the patients were compared between two groups;The quality of life of all patients were evaluated post-treatment,and the change of immunity indexes were compared and analyzed.Results:The VAS score of all patients was decreased significantly compared with pre-treatment (P＜0.05),and the score of Group B was lower than those patients in Group A (P＜0.05);The total remission rate of Group B was significantly higher than those of Group A (P＜0.05);after treatment,the score of appetite,emotion,sleep,daily activities,social communications of all patients decreased significantly compared with pre-treatment (P＜0.05),and the change of Group B was decrease significantly higher than those patients in Group A (P＜0.05);the immune index of two groups was significantly increased (P＜0.05),and the level of the indexes including IgG,IgA,IgM,CD4+,CD4+/CD8+ and circulating immune complex (CIC) increased compared with pre-treatment remarkably (P＜0.05),and which change in Group B was significantly higher than Group A (P＜0.05).Conclusions:Oxycontin combined with gabapentin for patients with neuropathic cancer pain deserved popularization in clinical,and which not only possessed well clinical effect,but also increased the quality of life.
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Objective: To optimize the formula and preparation process of docetaxel-loaded pluronic P123 micelles. Methods:Docetaxel-loaded pluronic P123 micelles were prepared by a thin-film hydration method and optimized by central composite design and response surface methodology. The influencing factors including the quantity of docetaxel, volume of organic phase, volume of hydra-tion and temperature of hydration were investigated with the entrapment efficiency as the index. The morphology of micelles was ob-served under a transmission electron microscope. The particle diameter and zeta potential were determined. The in vitro release property was measured by a dialysis method. Results:The relationship between the influencing factors and the evaluation parameter was fitted by multi-linear equation, quadratic polynomial equation and cubic polynomial equation, respectively. The results showed that the cubic polynomial equation was superior to the others according to the correlation coefficient. Docetaxel-loaded pluronic P123 micelles were spherical with the mean diameter, zeta potential, polydispersity index, encapsulation efficiency and drug loading of 108. 3 nm,-3. 99 mV, 0. 265, (97. 91 ± 0. 28)% and (3. 72 ± 0. 12)%, respectively. The cumulative release in vitro reached 95. 03% in 120 h, and docetaxel-loaded pluronic P123 micelles had notable sustained-release property. Conclusion: The technical process for do-cetaxel-loaded pluronic P123 micelles is simple and usable, and docetaxel-loaded pluronic P123 micelles show high encapsulation effi-ciency and notable sustained-release property.
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Objective To study the characteristics of the inpatients with cancer pain, the application of WHO three steps analgesic solution (three steps analgesic) and the application of traditional Chinese analgesic (TCM). Methods Retrospective investigation of distribution of cancer pain, situation of pain, application of TCM, and the application of conbination of three steps analgesic and TCM treatment, by using, clinical data from the oncology department of afflicated hospital of Liaoning university of TCM ranging from May, 2009 to June, 2010. Results 47.4% (517/1 090) of patiens were combined with cancer pain. Among the patients, majority were the middle-aged and old (59.19%) and male patients (57.63%). The abdominal pain (57.45%) and chest pain (37.91%) were topranks, and the distributions of pain period such assustainability (65.37%), moderately (53.38%), bloated pain (49.71%) and dull pain (29.98%) had larger proportion. The TCM excessive patterns(50.87%) were more than the TCM deficiency patterns (28.63%) or mixed TCM patters of excessive and deficiency patterns (20.50%). A total of 46 patients had mild pain, 76.09% of whom used TCM, 15.22% used first step drugs, and 8.69% used combination treatment, while 276 patients with moderate pain used second step analgesic, and 91.67%of them also used TCM, the rest195 patients with severe pain used third step analgesic, and 55.38%of them also used TCM. The time of pain release of TCM alone or combination of TCM and three steps analgesic were longer than the three steps analgesic alone. Conclusions Early intervention of traditional Chinese medicine on the patients with mild pain could reduce the dose of first step analgesic drugs, and TCM application at the second step could delay the speed of transtformfrom second to third step pain, and TCM could prevent the side effects of morphine when patients were with severe pain.
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OBJECTIVE:To study the cytotoxicity of the graft polymer after polyethyleneimine (PEI) had been modified by polyoxyethylene stearate (POES) and the property of the carrier,grafted-polymer/DNA complexes. METHODS: To modify PEI by conjugating PEI to POES with succinimidyl carbonate method. Structural analysis of synthesized polymer was performed by using 1H-NMR. Agarose gel electrophoresis (AGE) behavior of the graft polymer/DNA complexes was observed with particle size and zeta potential measured. The cytotoxicity of the graft polymer was evaluated by MTT method. The pGL3-lus served as a reporter gene,and the luciferase activity was determined to evaluate the transfection efficiency of grafted-polymer/DNA on Hela cells. RESULTS: 1H-NMR showed that the graft polymer had high purity. AGE showed that the DNA-wrapping ability of the graft polymer were increased with the increase of N/P ratios,and decreased with the increase of the POES graft number. The size of complexes was below 300 nm,and the zeta potential of the complexes increased with the increase of N/P ratios. The graft polymer showed significantly lower cytotoxicity than PEI. The graft polymer with lower POES graft number had higher transfection efficiency. CONCLUSIONS: The POES-modified PEI can be used as an effective non-viral genetic carrier.
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Objective:To observe the stability of thymosin ?_1 microspheres under preparation conditions.Methods: Using HPLC method,we investigated the influence of different temperatures(-20 ℃, 6-8℃,60℃),sonification time(10-60 s) and pH values (pH 4.0,7.0 and 10.0) on thymosin ?_1 stability.Results: Under the conditions of frozen environment(-20℃) and refrigeration(6-8℃), thymosin ?_1 remained stable for 30 d.Thymosin ?_1 did not degrade in 60℃ water bath for 12 h or in phosphate buffer solution(PBS,pH 4.0) under 37℃ for 14 h.The sonification time within 60 s was found to be safe for the preparation.Conclusion: Thymosin ?_1 is stable under these preparation conditions.
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Objective:To prepare injectable interferon ?-2b(IFN-?-2b) loaded microsphere and develop a long-acting dosage form.Methods: IFN-?-2b loaded microspheres were prepared with poly(lactic-co-glycolic acid)(PLGA) as carrier material by double emulsion(w/o/w) method and solid in oil in oil(s/o/o) method separately.Physical and chemical characteristics of microspheres(mean diameter,morphology and drug entrapment efficiency) were evaluated;the in vitro release behavior and influencing factors of the microspheres were determined by micro-BCA(bicinchoninic acid) method;and IFN-?-2b stability during encapsulation and in vitro release was evaluated by sodium dodecyl sulfate polyacrylamide gel electropheresis.Results: The 2 types of microspheres produced had good shape and dispersive quality and a drug entrapment efficiency of more than 80%.IFN-?-2b bulk ultrafitration can significantly influence the mean diameter and in vitro release behavior of microspheres prepared by w/o/w method.The accumulated release(within 1 month) of the microspheres prepared by both methods was significantly improved when using PLGA with lower inherent viscosity.SDS-PAGE test showed aggregation of IFN-?-2b with s/o/o method,while there was no difference between the electrophoretic behavior of bulk IFN-?-2b and IFN-?-2b in microspheres prepared by w/o/w method.Conclusion: IFN-?-2b can be encapsulated into injectable microspheres to yield a one-month continuous release by both w/o/w method and s/o/o method.