Poloxamer188复合载多西紫杉醇聚L-乳酸电纺纤维的制备及表征
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摘要
目的考察均相纺丝条件下,Poloxamer188复合量对聚L-乳酸电纺纤维中多西紫杉醇释放的影响。方法将多西紫杉醇、Poloxamer188、聚L-乳酸共同溶解在二氯甲烷中形成均相溶液后静电纺丝。采用扫描电子显微镜观察纤维形态,X-射线衍射、差示热分析、傅里叶变换红外光谱表征三者的符合情况,采用高效液相色谱-紫外分光光度发法测定水释放介质中多西紫杉醇的含量,绘制释放曲线并采用Freundlich方程式进行拟合。结果 Poloxamer188的复合量越高,多西紫杉醇的突释量和14 d后的释放量越高,突释部分为混悬微晶,缓释部分为澄清溶液。Poloxamer188的复合量在60%以上时,能够得到无珠子、直径较为均一的纤维,纤维表面有结晶态的Poloxamer188存在;Poloxamer188的复合量达到70%以上时,释放曲线有明显的缓释相;Poloxamer188的复合量为100%时,多西紫杉醇的相对释放百分率达到58%。多西紫杉醇的释放曲线可用Freundlich方程式进行拟合。结论多西紫杉醇-Poloxamer188-聚L-乳酸均相溶液电纺复合纤维中,Poloxamer188促进了多西紫杉醇的释放。
Objective To investigate the effect of Poloxamer188 complexing amount to release of docetaxel which was incorporated within poly L-lactic acid homogeneous solution-electrospun fibers. Methods Docetaxel,Poloxamer188 and poly L-lactic acid were dissolved within dichloromethane to form homogeneous solution and to be electrospun to form fibers. The morphology of fibers was characterized by scanning electron microscope. Complexation of three materials was characterized by X-ray diffraction,differential thermal analysis and Fourier transform infrared spectrum. Docetaxel amount in water release medium was determined by high performance liquid chromatography-ultra-violet spectrometry,and the release curves were drewand regressed. Results No-beads fibers of homogeneous diameters could be obtained when the complexing amount of Poloxamer188 was above 60%,there was Poloxamer188 of crystalline state existing on the fibers surface. The more Poloxamer188 complexing amounts were,the more burst release amount and after 14 d release amount were. Burst released docetaxel were crystalline suspensions while the sustained released docetaxel were transparent solutions. When Poloxamer188 complexing amount was above 70%,there became to be obvious sustained release phase. When Poloxamer188 complexing amount was 100%,the relative percentage release ratio could be 58%. Docetaxel release curves could be regressed by Freundlich's equation. Conclusion Poloxamer188 facilitated the release of docetaxel in docetaxel-poloxamer188-poly lactic acid homogeneous solution electrospun fibers
Objective To investigate the effect of Poloxamer188 complexing amount to release of docetaxel which was incorporated within poly L-lactic acid homogeneous solution-electrospun fibers. Methods Docetaxel,Poloxamer188 and poly L-lactic acid were dissolved within dichloromethane to form homogeneous solution and to be electrospun to form fibers. The morphology of fibers was characterized by scanning electron microscope. Complexation of three materials was characterized by X-ray diffraction,differential thermal analysis and Fourier transform infrared spectrum. Docetaxel amount in water release medium was determined by high performance liquid chromatography-ultra-violet spectrometry,and the release curves were drewand regressed. Results No-beads fibers of homogeneous diameters could be obtained when the complexing amount of Poloxamer188 was above 60%,there was Poloxamer188 of crystalline state existing on the fibers surface. The more Poloxamer188 complexing amounts were,the more burst release amount and after 14 d release amount were. Burst released docetaxel were crystalline suspensions while the sustained released docetaxel were transparent solutions. When Poloxamer188 complexing amount was above 70%,there became to be obvious sustained release phase. When Poloxamer188 complexing amount was 100%,the relative percentage release ratio could be 58%. Docetaxel release curves could be regressed by Freundlich's equation. Conclusion Poloxamer188 facilitated the release of docetaxel in docetaxel-poloxamer188-poly lactic acid homogeneous solution electrospun fibers
引文
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[24]XU X,CHEN X,XU X,et al. BCNU-loaded PEG-PLLA ultrafine fibers and their in vitro antitumor ac-tivity against glioma C6cells[J]. Journal of Con-trolled Release,2006,114(3):307-316.
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[28]崔银,张天,蔡东,等. Tween-80复合聚L-乳酸电纺纤维的制备及表征[J].中国医药工业杂志,2018,(1):82-88.
[29]王浩,温梦,蔡东,等.度米芬聚L-乳酸电纺纤维膜的制备及表征[J].沈阳药科大学学报,2017,34(4):290-295.
[30]王浩,康卫民,张亚秋,等.壬苯醇醚聚己内酯电纺纤维膜的表征及释放[J].沈阳药科大学学报,2015,32(4):249-255.
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[35]王浩,宋宏锐,邓英杰,等.聚α-羟基辛酸对W/O乳液电纺聚乳酸纤维毡中阿霉素释放的影响[J].合成化学,2010,18(3):273-279.
[36]王浩,邓英杰,焦自学,等.聚L-乳酸与聚乙二醇-b-聚L-乳酸电纺纤维中布洛芬的释放[J].沈阳药科大学学报,2010,27(9):686-694.
[37]XU X,YANG L,XU X,et al. Ultrafine medicated fi-bers electrospun from W/O emulsions[J]. Journal ofControlled Release,2005,108(1):33-42.
[2] BERNARD C H,PIERRE F U,KERBRAT P,et al.Docetaxel is a major cytotoxic drug for the treatmentof advanced breast cancer:a phase II trial of the clini-cal screening cooperative group of the European or-ganization for research and treatment of cancer[J].Journal of Clinical Oncology,1995,13(2):314-315.
[3]吴洪斌,陆益.多西紫杉醇的不良反应及预防处理[J].药物不良反应杂志,2004,6(4):248-250.
[4]曹熙.多西紫杉醇聚合物胶束的研究进展[J].中国新药杂志,2017,26(10):1137-1143.
[5] ZHAO P,ASTRUC D. Docetaxel nanotechnology inanticancer therapy[J],Chem M edchem,2012,7(6):952-972.
[6]张学农,张强.紫杉烷类新剂型的研究进展及其临床应用[J].国外医学(药学分册),2002,29(6):321-324.
[7] KIM H. Parenteral docetaxel emulsion system and itsstability[J]. Journal of Pharmaceutical Investigation,2009,39(1):13-18.
[8] CHONG R,KIM H M,LEE P,et al. Preparation andstability evaluation of docetaxel-loaded oral liposome[J]. Journal of Pharmaceutical Investigation,2010,40(2):85-90.
[9] ZHENG Y,CHENG Y,CHEN J,et al. Injectable hy-drogel-microsphere construct w ith sequential degra-dation for locally synergistic chemotherapy[J]. Ap-plied M aterials and Interfaces,2017,9(4):3487-3496.
[10] FAN R R,WANG Y L,HAN B,et al.,Docetaxelload biodegradable porous microspheres for the treat-ment of colorectal peritoneal carcinomatosis[J]. Inter-national Journal of Biological M acromolecules,2014,69:100-107.
[11] GAO Y,REN F,DING B,et al. Thermo-sensitivePLGA-PEG-PLGA hydrogel for sustained releaseof docetaxel[J]. Journal of Drug Targeting,2011,19(7):516-527.
[12]陈洁,邱利焱,胡敏新,等.多西紫杉醇固体分散体的制备和体内外研究[J].中国药学杂志,2007,42(22):1717-1722.
[13]王军飞,张伟,丁宁,等.紫杉醇类前药的研究进展[J].中国药物化学杂志,2010,20(5):394-402.
[14] DANCKWERTS M,FASSIHI A. Implantbable con-trolled release drug delivery system:a review[J].Drug Development and Industrial Pharmacy,1991,17(11):1465-1466.
[15]MCKENZIE M,BETTS D,SUH A,et al. Hydrogel-based drug delivery systems for poorly w ater-solubledrugs[J]. M olecules,2015,20(11):20397-20408.
[16]SIDAWAY P. Localized docetaxel delivery is feasible[J]. Nature Reviews Urology,2017,14(10):585-586.
[17]张志云,黄宇彬,景遐斌.用于原位癌症治疗的电纺纤维毡[C].全国高分子学术论文报告会,2015.
[18]KENAWY E R,ABDEL HAY F I,MEWEHY M H,et al. Processing of nanofibers through electrospinningas drug delivery systems[J]. M aterial Chemistry andPhysics,2009,113(1):296-302.
[19]ZENG J,YANG L. Influnce of the drug compatibilityw ith polymer solution on the release kinetics of elec-trospun fiber formulation[J]. Journal of ControlledRelease,2005,105(1/2):43-51.
[20]MEINEL A J,GERMERSHAUS O,LUHMANN T,etal. Electrospun matrices for localized drug delivery:current technologies and selected biomedical applica-tions[J]. European Journal of Pharmaceutics and Bio-pharmaceutics,2012,81(1):1-13.
[21]HU X L,LIU S,ZHOU G Y. Electrospinning of poly-meric nanofibers for drug delivery applications[J].Journal of Controlled Release,2014,185(1):12-21.
[22]MEI L,WANG Y L,TONG A P,et al. Facile electro-spinning of an efficient drug delivery system[J]. Ex-pert Opinion on Drug Delivery,2016,13(5):741-753.
[23]WANG X,LIU J,WANG H,et al. Influencing factorsof preparation of polylactic acid nanofiber via electro-spinning[J]. Polymer M aterials Science and Engineer-ing,2014,30(8):161-166.
[24]XU X,CHEN X,XU X,et al. BCNU-loaded PEG-PLLA ultrafine fibers and their in vitro antitumor ac-tivity against glioma C6cells[J]. Journal of Con-trolled Release,2006,114(3):307-316.
[25] ZENG J,XU X,CHEN X,et al. Biodegradable elec-trospun fibers for drug delivery[J]. Journal of Con-trolled Release,2003,92(3):227-231.
[26]HU J,PRABHAKARAN M P,DING X,et al. Emul-sion electrospinning of polycaprolactone:influence ofsurfactant type tow ards the scaffold properties[J].Journal of Biomaterials Science-Polymer Edition,2015,26(1):57-75.
[27]王浩,崔银,温梦,等. Polomaxer188复合聚L-乳酸电纺纤维的制备及表征[J].沈阳药科大学学报,2018,35(3):155-162.
[28]崔银,张天,蔡东,等. Tween-80复合聚L-乳酸电纺纤维的制备及表征[J].中国医药工业杂志,2018,(1):82-88.
[29]王浩,温梦,蔡东,等.度米芬聚L-乳酸电纺纤维膜的制备及表征[J].沈阳药科大学学报,2017,34(4):290-295.
[30]王浩,康卫民,张亚秋,等.壬苯醇醚聚己内酯电纺纤维膜的表征及释放[J].沈阳药科大学学报,2015,32(4):249-255.
[31]王浩,温梦,康卫民,等. W/O乳液静电纺丝法制备盐酸环丙沙星聚L-乳酸纤维膜及表征[J].沈阳药科大学学报,2016,33(6):426-437.
[32]XU W,ATALA A,YOO J J,et al. Controllable dualprotein delivery through electrospun fibrous scaffoldsw ith different hydrophilicities[J]. Biomedical M ateri-als,8(1):SI.
[33]方亮.药剂学[M].第八版.北京:人民卫生出版社,2016:66-69.
[34]杨蓓,郑璐侠,段更利,等.高效液相色谱法测定多西紫杉醇注射液含量及其有关物质[J].复旦学报,2006,33(5):701-703.
[35]王浩,宋宏锐,邓英杰,等.聚α-羟基辛酸对W/O乳液电纺聚乳酸纤维毡中阿霉素释放的影响[J].合成化学,2010,18(3):273-279.
[36]王浩,邓英杰,焦自学,等.聚L-乳酸与聚乙二醇-b-聚L-乳酸电纺纤维中布洛芬的释放[J].沈阳药科大学学报,2010,27(9):686-694.
[37]XU X,YANG L,XU X,et al. Ultrafine medicated fi-bers electrospun from W/O emulsions[J]. Journal ofControlled Release,2005,108(1):33-42.
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