| Background and objectivesGlioma is the most common intracranial malignant tumor.Surgery is fully complete removal of the tumor is one of the main factors affecting the prognosis of patients with glioma.Because invasive glioma growth, preoperative examination and intraoperative microscope difficult to determine the accurate positioning and the tumor and normal tissue boundaries, surgery is difficult to completely removed, easy to relapse after the operation, the prognosis is poor. Surgical adjuvant radiotherapy for synchronous mo thiazole amine chemotherapy is one of the new standard solution in the diagnosis of glioma. Abroad, however, related studies have shown that the standard treatment of benefit in patients with newly diagnosed glioblastoma survival, but the median survival period was only 14.6 months and 5 years survival rate is only 9.8%, the survival time is very limited, curative effect is difficult to satisfactory. Glioma is a major disease seriously affect human health. As the operating microscope, neurosurgery navigation technology is widely used, as well as ultrasound, CT and MRI in positioning technology development and application of glioma surgery cut all rate increased. Owing to the high cost of equipment, is still difficult to clinical widely.Kinetic energy of light and photosensitizer intraoperative localization technology in recent years began to clinical applications, but also exist surrounding tumor surgery ooze blood imaging light green fluorescence. At present, the widely used 5-amino ketones pentanoic acid (5-ALA) mediated second-generation photosensitizer intraoperative need blue, make the glioma cells glow red, application is very limited. With the development of new type of molecular biotechnology, molecular biological fluorescent agent or nanometer stain may become the new fluorescent agent, is expected to be as glioma intraoperative localization of new development direction.How to determine the boundary of the gliomas, in the case of as less as possible to remove the normal brain tissue completely resected gliomas, improve tumor resection rate and reduce damage neurosurgeons are facing a big problem, the concept of nanometer stain is put forward to provide the possibility.Materials and methodsPrecision weigh the prescriptions of soybean lecithin, temozolomide and fetal bovine serum liquid centrifugal supernatant fluid, the two unsymmetrical-NH PEG solution to join 3ml cyclohexane solution, the ultrasonic oscillation, make each substances dissolved in cyclohexane. To join in solution prescriptions of genipin, carries on the oscillation after ultrasonic put solution in 40℃ water bath pot, magnetic stirring, for a certain time of crosslinking. Will be the completion of the crosslinking solution connected to the rotary evaporation apparatus, removal of cyclohexane, then add 3 ml purified water,and oscillation ultrasound, namely the stain solution made from blue. Will be made of the nanoscale blue stain solution in 40℃ environment about 2h, remove access to the lyophilizer after 48 h, nanoscale producing dye into the blue of the glioma. According to the blue of the glioma nanoscale stain producing method, experiment with orthogonal experiment method prescription screening, screening the best prescription preparation. Choose the nanoscale stain on the blue of the glioma producing influence during the preparation of magnetic stirring speed, the temperature of water bath, the crosslinking time, optimized choice respectively.For the preparation of the optimal solution using the Blue Nanoscale Coloring Agent of a glioma (nano lipoprotein of temozolomide) producing average nano particle size, average charge tests respectively, and the morphology, producing morphology under the electron microscope, the morphology in the aqueous solution, PH value, and the stability is examined. SD rat glioma model is established and the Blue Nanoscale Coloring Agent of a glioma (nano lipoprotein of temozolomide) is used to test the dyeing.Result1.Preparation of Blue Nanoscale Coloring Agent of a glioma (nano lipoprotein of temozolomide) optimum prescription for 60mg soybean lecithin, fetal bovine serum 900 μL, double amino PEG 10 mg·ml-1, temozolomide 2mg·ml-1, genipinl.5mg·ml-1.2.Preparation of glioma in nanoscale blue stain in the process of optimizing process are:magnetic stirring speed is 400 RPM, water bath temperature of 40℃, the crosslinking time of 48 h.3.Glioma of nanoscale blue stain aqueous solution under the electron microscope form basic assumes the circular uniform and dispersed evenly, observed by naked eye without particles and debris; Blue Nanoscale Coloring Agent of a glioma (nano lipoprotein of temozolomide) freeze-dried powder observed by naked eye view is powder or granule.4.Glioma of nanoscale blue stain of the aqueous solution PH value of 5.72, PH value of 5.85 after diluted 10 times,100 times dilution after PH 6.026, PH value of 6.163 after diluted 1000 times.5.Glioma of nanoscale blue stain good stability and placed after six months, the particle size of basically the same.6.1n animal experiments have obvious dyeing effect, meet the glioma blue stain in nanometer scale production effect and the production purpose.7.Glioma of nanoscale blue stain can keep stable in aqueous solution at the 24 h, for mo thiazole amine nano lipoprotein producing drug coating at a rate of 25.97%, for mo thiazole amine nano lipoprotein producing drug loadings is: 0.575%.Conclusion1.Glioma blue nanoscale particle size of 100-nm or less dye, is easy to penetrate biofilm physiological barrier ability, can quickly reach the tumor tissue, and cell contact area is large, can be more steady contact with tumor tissue and consumed by the tumor cells.2.Glioma of nanoscale blue stain can be dyed blue tumor tissue, do not need special operating room and with the aid of additional equipment, in normal light and ordinary in the operating room, staff will be able to distinguish between tumor tissue and normal tissue to the naked eye, to facilitate accurate resection of the tumor in the operation.3.Glioma of nanoscale blue stain of good stability, placed after six months, the particle size of basically the same.4.The blue of the glioma nanoscale stain of easy accessible raw materials, low cost, the preparation method is simple, to large-scale chemical production. |
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