静电纺载药聚乳酸超细纤维及其缓释性研究
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摘要
静电纺丝技术是目前制备超细纤维最重要的方法之一,其制备的超细纤维具有纤维纤度小、比表面积大、孔隙率高等特点,因而具有广泛用途,尤其在生物医学领域,静电纺超细纤维可用作组织工程支架、药物传输与缓控释放的载体及创伤敷料等。但由于静电纺丝过程的复杂性和实验参数的多样性,制备直径分布范围窄的纤维一直是静电纺丝的难点之一,另外,以静电纺超细纤维作为药物传输与释放载体的研究刚刚起步,属于医药领域较新的课题之一。
论文以可生物降解高分子材料聚乳酸(PLA)作为药物载体,以吲哚美辛、阿司匹林、利福平作为药物模型,分别共混进行静电纺丝,系统地研究了纺丝工艺参数、不同药物的加入、不同药物含量对所制得超细纤维形貌结构的影响。采用红外光谱(IR)和差热(DTA)分析法研究PLA中加入药物后对超细纤维微细结构的影响。利用体外释药方法,采用紫外分光光度计测试并研究了静电纺PLA/吲哚美辛、PLA/阿司匹林、PLA/利福平及丝素/利福平超细纤维的释药行为。结果表明:
(1)PLA能溶解于三氯甲烷与丙酮的混合溶剂中,呈均匀的纺丝液。随着纺丝液质量分数的减小、电压和极距的增大,纤维的直径逐渐减小;
(2)三种药物(吲哚美辛、阿司匹林、利福平)的加入提高了PLA静电纺丝的可纺性,并使纤维直径变细;随着药量的增加,纤维平均直径更减小;
(3)药物与PLA主要为共混物理结合,大部分药物被包埋在静电纺超细纤维内部;
(4)静电纺PLA超细纤维对药物具有明显的缓释性能:3h纯药粉全部释放完毕,而PLA/药物超细纤维在48h内的累积释药百分率为50%～80%;随着PLA质量分数的增加,释药速率减慢;随着含药量的增加,释药速率增快;
(5)疏水性材料PLA超细纤维对三种模型药物的释放机理主要为纯Fick扩散机理;同样作为利福平的载体,PLA比亲水性材料丝素超细纤维具有更好的缓释效果。
Electrospinning is one of the most important technique to produce ultrafine fibers. Because ultrafine fibers have several useful properties including small diameter、high surface area to volume ratio and high porosity, they can be used extensively, especially in biomedical fields such as tissue engineering scaffolds, drug delivery and controlled release, wound dressing and so on. However, due to the complexity of the electrospinning process and the diversity of the electrospinning parameters, one of the challenges in electrospinning is the preparation of the electrospun fibers with narrow diameter distribution. Moreover, the research of electrospun fibers in drug delivery and controlled release was developed recently and it belongs a new thesis in medicine fields.
This thesis made a preliminary research on the electrospun biodegradable PLA ultrafine fibers containing three different model drugs (indomethacin (IND)、aspirine (ASP) and rifampin (RFP)). The author systematically studied the influence of electrospinning parameters, the addition of three different model drugs and different amounts on fiber’s morphology and structure. The influence of the addition of drugs on microstructure of electrospun PLA ultrafine fibers was also tested and analyzed by means of IR and DTA. The author used UV-spectrophotometer to characterize the release of electrospun PLA/IND、PLA/ASP、PLA/RFP and silk fibroin(SF)/RFP ultrafine fibers and studied them by means of in vitro release.
The results showed that:
(1) PLA could be dissolved in the mixture of chloroform and acetone(2︰1 in volume) to make even spinning solution. The fiber’s diameter was reduced with the concentration of spinning solution decreasing、voltage and electrode distance increasing.
(2) The addition of three different drugs could improve the electrospinning process of PLA and reduced the fiber’s diameter. The fiber’s diameter was also reduced by adding the amount of IND、ASP、RFP.
(3) The drugs were physically mixed with PLA respectively. Most of the drugs were encapsulated within the fibers.
(4)Electrospun PLA ultrafine fibers had obvious sustained release pattern: The pure drugs finished release within three hours, whereas the cumulative drug release percentage of drug loaded PLA ultrafine fibers is from 50 to 80 percent.The release rate of PLA/IND、PLA/ASP and PLA/RFP were slow with increasing PLA concentration , whereas they were more rapid when the amount of drug increased.
(5)The release mechanism of three different model drugs from PLA ultrafine fibers were followed by Fick’s law for diffusion. Two different biodegradable materials were used as skeletal base materials for production of RFP loaded ultrafine fibers , the hydrophobic PLA ultrafine fibers had a more sustained release pattern than hydrophilic SF during the same period.
论文以可生物降解高分子材料聚乳酸(PLA)作为药物载体,以吲哚美辛、阿司匹林、利福平作为药物模型,分别共混进行静电纺丝,系统地研究了纺丝工艺参数、不同药物的加入、不同药物含量对所制得超细纤维形貌结构的影响。采用红外光谱(IR)和差热(DTA)分析法研究PLA中加入药物后对超细纤维微细结构的影响。利用体外释药方法,采用紫外分光光度计测试并研究了静电纺PLA/吲哚美辛、PLA/阿司匹林、PLA/利福平及丝素/利福平超细纤维的释药行为。结果表明:
(1)PLA能溶解于三氯甲烷与丙酮的混合溶剂中,呈均匀的纺丝液。随着纺丝液质量分数的减小、电压和极距的增大,纤维的直径逐渐减小;
(2)三种药物(吲哚美辛、阿司匹林、利福平)的加入提高了PLA静电纺丝的可纺性,并使纤维直径变细;随着药量的增加,纤维平均直径更减小;
(3)药物与PLA主要为共混物理结合,大部分药物被包埋在静电纺超细纤维内部;
(4)静电纺PLA超细纤维对药物具有明显的缓释性能:3h纯药粉全部释放完毕,而PLA/药物超细纤维在48h内的累积释药百分率为50%～80%;随着PLA质量分数的增加,释药速率减慢;随着含药量的增加,释药速率增快;
(5)疏水性材料PLA超细纤维对三种模型药物的释放机理主要为纯Fick扩散机理;同样作为利福平的载体,PLA比亲水性材料丝素超细纤维具有更好的缓释效果。
Electrospinning is one of the most important technique to produce ultrafine fibers. Because ultrafine fibers have several useful properties including small diameter、high surface area to volume ratio and high porosity, they can be used extensively, especially in biomedical fields such as tissue engineering scaffolds, drug delivery and controlled release, wound dressing and so on. However, due to the complexity of the electrospinning process and the diversity of the electrospinning parameters, one of the challenges in electrospinning is the preparation of the electrospun fibers with narrow diameter distribution. Moreover, the research of electrospun fibers in drug delivery and controlled release was developed recently and it belongs a new thesis in medicine fields.
This thesis made a preliminary research on the electrospun biodegradable PLA ultrafine fibers containing three different model drugs (indomethacin (IND)、aspirine (ASP) and rifampin (RFP)). The author systematically studied the influence of electrospinning parameters, the addition of three different model drugs and different amounts on fiber’s morphology and structure. The influence of the addition of drugs on microstructure of electrospun PLA ultrafine fibers was also tested and analyzed by means of IR and DTA. The author used UV-spectrophotometer to characterize the release of electrospun PLA/IND、PLA/ASP、PLA/RFP and silk fibroin(SF)/RFP ultrafine fibers and studied them by means of in vitro release.
The results showed that:
(1) PLA could be dissolved in the mixture of chloroform and acetone(2︰1 in volume) to make even spinning solution. The fiber’s diameter was reduced with the concentration of spinning solution decreasing、voltage and electrode distance increasing.
(2) The addition of three different drugs could improve the electrospinning process of PLA and reduced the fiber’s diameter. The fiber’s diameter was also reduced by adding the amount of IND、ASP、RFP.
(3) The drugs were physically mixed with PLA respectively. Most of the drugs were encapsulated within the fibers.
(4)Electrospun PLA ultrafine fibers had obvious sustained release pattern: The pure drugs finished release within three hours, whereas the cumulative drug release percentage of drug loaded PLA ultrafine fibers is from 50 to 80 percent.The release rate of PLA/IND、PLA/ASP and PLA/RFP were slow with increasing PLA concentration , whereas they were more rapid when the amount of drug increased.
(5)The release mechanism of three different model drugs from PLA ultrafine fibers were followed by Fick’s law for diffusion. Two different biodegradable materials were used as skeletal base materials for production of RFP loaded ultrafine fibers , the hydrophobic PLA ultrafine fibers had a more sustained release pattern than hydrophilic SF during the same period.
引文
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