壳聚糖—海藻酸钠聚电解质膜的制备及性能调控研究
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摘要
由于聚电解质复合物( Polyelectrolyte Complexes, PEC )的特殊性能,聚电解质复合物在药物控释领域应用的研究引起了重视,并在刺激响应药物控释、细胞免疫隔离移植、多肽蛋白质药物的控释、基因治疗及人造疫苗等领域取得了较大的进展。利用在水溶液中,带有相反电荷的多糖能形成聚电解质复合物的性质,壳聚糖作为典型的聚阳离子电解质,可与聚阴离子电解质海藻酸钠通过静电作用形成聚电解质复合物,这种性质被应用在片剂包衣、海绵、微球、微囊等的制备中。但是在微胶囊、微珠或包衣中,这种复合物以膜的形式原位形成,很难分离和表征。而且国内外对聚电解质复合物成膜的特性一直没有详细阐述。为解决这一问题,本实验以壳聚糖、海藻酸钠为基材,将这种聚电解质复合物制成膜并对其性能进行研究。
本文采用溶剂挥发法制备壳聚糖-海藻酸钠聚电解质复合膜,对铸膜液性质和聚电解质膜有关特性进行研究。利用OM、SEM考察其共混状态和外观形貌,用FTIR和XRD等表征方法对基团键合、结晶情况进行分析,尤其对力学特性、吸水性、吸湿性、透光性等作了较为深入的研究,以磺胺嘧啶银为模型药物考察膜的体外释放行为,并对影响药物释放的有关因素进行分析,以期在壳聚糖-海藻酸钠聚电解质作为药物控释载体的应用方面有所进展。
本文的主要研究内容和结论如下:
1.采用相转化溶剂挥发法,以壳聚糖、海藻酸钠为基材制备壳聚糖-海藻酸钠聚电解质膜。FTIR结果显示,壳聚糖和海藻酸钠在共混后,均发生基团特征吸收峰的位移,表明壳聚糖的功能基团与海藻酸钠的功能基团发生了相互作用。XRD分析结果表明,壳聚糖膜在18.7°和22.5°出有峰值,分别代表水合和脱水晶形,海藻酸钠膜在15.2°和22.5°处有结晶峰。而共混后,这种复合膜显示无规则结构,这种现象可以解释为壳聚糖和海藻酸钠高分子链间的强烈静电相互作用破坏了壳聚糖或海藻酸钠分子形成的规则晶形结构。
2.采用溶液共混的方法,考查溶液粘度性质。在实验中,对于极稀溶液及高浓度壳聚糖和海藻酸钠溶液,在共混过程中,共混溶液均出现黏度最大值,而且用这种溶液铸膜,膜的力学性能及吸水、透气等性能都与溶液粘度性质有关。当海藻酸钠溶液中含有离子交联剂钙离子浓度为0.02%时,溶液显示负触变性。
3.对壳聚糖-海藻酸钠聚电解质膜的力学性能方面进行考查。相关实验结果表明,共混溶液浓度和配比对膜的力学性能有重要影响。对于用极稀溶液配制的聚电解质膜,当海藻酸钠的含量为50%时,共混液的黏度达最大值224cps,铸膜后,干膜有最大断裂强度52.16 MPa,湿膜有最大断裂伸长率为46.28%,综合显示聚电解质复合物的形成对聚电解质膜的性能有重要影响。离子交联剂钙离子的存在以及配制溶液时溶剂的极性都会对聚电解质膜的力学性能产生影响。加入不同浓度的钙离子后,膜的刚性增加,这可能与钙离子在海藻酸钠的羧基之间建立桥连有关。降低溶剂极性能有效降低聚电解质复合物的生成速率。在较低极性的溶液中,壳聚糖分子链成卷曲状,减少了与海藻酸钠分子链的链间相互作用。从结果可以看出,随着溶剂极性的降低,聚电解质膜的力学强度下降,脆性增加。
4.对壳聚糖-海藻酸钠聚电解质膜的吸水、透光/气性、刺激响应方面进行研究。实验结果显示,这种聚电解质膜显示pH响应和离子强度响应的吸水特性,在低pH和高pH外界环境下,聚电解质膜均显示膨胀吸水特性;此聚电解质膜在湿态下可看做离子性凝胶,随着外界溶液离子强度的增大,凝胶膨胀吸水减少,这可能与离子凝胶内外渗透压差减小有关,减少了极性水分子的渗入,而且当NaCl浓度达到0.2M时,基质膜的吸水率不再发生显著变化。为了更清晰说明在两种材料的配比为1:1时生成的聚电解质复合物对聚电解质膜性能的影响,本实验考查了钙离子、溶剂极性、配比和铸膜液放置时间对聚电解质膜的WVTR的影响。结果显示,当钙离子含量为0.01%时,聚电解质膜的水蒸汽透过率最大。这可能与溶剂极性降低后,高分子链蜷曲,减少了高分子链基团间的相互作用,从而增加了高分子链间的孔隙,利于水蒸汽透过,导致聚电解质膜水蒸汽透过率增加有关。对于纯膜,其WVTR均显示较高值,而对于对于复合膜,只有配比为1:1时的复合膜显示较高的WVTR,与其他配比相比,有显著差异(p<0.05),这可能与聚电解质生成量较多,导致更多多孔网状结构,更利于水蒸汽的透过有关。本实验制备的聚电解质膜的WVTR从442至618 g/m2/day,可以通过组分配比调节膜的WVTR。随着铸膜液放置时间的延长,聚电解质膜的WVTR下降,可能是因为对于新鲜配制的铸膜液,两种高聚物中的氨基基团和羧基基团由于空间位阻的作用而没充分接触键合。而在放置过程中,壳聚糖和海藻酸钠的高分子链旋转伸展,有利于未反应的功能基团接触反应。结果是放置一段时间的铸膜液高分子之间相互作用更强,导致形成的聚电解质膜的结构更致密,因此WVTR随着放置时间的延长而显著下降。在透光实验中,壳聚糖膜/海藻酸钠聚电解质膜膜显示具有优良的透光性能。
5.体外药物释放实验中,当海藻酸钠的含量为50%时,药物的累积释放量最大,相同时间内释放的药物最快最多,此时的凝胶具有不溶于水的,有弹性的多孔的网状结构。随着载药量的增加,药物的释放不是同步增加的,载药量为15%时,药物累计释放量反而下降,这可能与药物的扩散系数有关。
本实验采用相转化溶剂挥发法,以壳聚糖、海藻酸钠为基材制备了壳聚糖-海藻酸钠聚电解质膜,并利用不同的测试方法对膜的性能进行测试和评价,对影响聚电解质膜性能的因素进行分析。制备过程简单温和,为其在胃肠道药物释放载体、生物活性物质的控释载体、辅料、组织工程、透析、包装以及包衣等领域的应用提供实验依据。
Due to its special properties, polyelectrolyte complexes ( PEC ) have been given much attention in drug control release areas and have made great progress in stimulating-reaction drug control release, cell immunity-isolation transplant, controlling release of peptide drug, gene therapy and man-made vaccine. In aqueous surroundings, polyasaccharides carrying opposite charges could form PEC. Polybase chitosan and polyacids sodium alginate can form PEC through ionic bonds. This property has been applied in tablet coating, sponge, microsphere and microbeads, but it is difficult to separate from microbeads, microspheres and tablet coating for the site-forming. It is not detailedly expatiated the properties of the membranes formation in present research. In order to solve the problem, we prepared the PEC membranes and investigated its properties using chitosan and sodium alginate.
Membranes of chitosan and alginate were prepared via a casting/solvent evaporation technique. This study investigated the characteristics of blend solutions and drug release properties of PEC membranes. Blendjing states and morphology were observed by OM and SEM. Intermolecular interactions in PEC films have been studied by Fourier transform infrared spectroscopy (FT-IR) and crystal states were measured by XRD. We specially investigated the mechanical characteristics, water-absorbability, moisture absorption, light transmission of the PEC. Aiming at making advanced progress in drug cotrolled carrier, the drug release property was studied by using silver sulfadizine as model drug and the influencing factors were analysed.
The main contents and conclusions are as follows:
1. Blended membranes and drug loaded membranes based on chitosan and alginate were produced by a casting/solvent evaporation method. FTIR results indicated that intermolecular interactions appeared in chitosan-alginate PEC membranes. The chitosan membrane showed two peaks at 18.7°and 22.5°related to the hydrated and anhydrated crystals, respectively. The diffractogram of alginate membrane consisted of two crystalline peaks at 15.2°and 22.5. After complexing, the typical peaks of chitosan disappeared and the PEC showed an amorphous morphology. This can be explained by the strong interactions between chitosan and alginate which had destroyed the close packing of the chitosan or alginate molecules for the formation of regular crystallites.
2. The viscosity properties of blended solutions were analysed. Low-concentration and high concentration of chitosan and alginate blend solution both presented the maximum value in viscosity, which were related to the PEC membranes properties. Sodium alginate with 0.02%w/v CaCl2 exhibited thixotropy-negative.
3. Mechanical properties of chitosan-alginate PEC membranes were tested. Correlated experiments showed that the solution concentration and compostion played important role in mechanical properties. The blended solution viscosity reached the maximum value of 224 cps with 50% w/w sodium alginate concentration. Meanwhile, the dry membrane has maximum breaking stess of 52.16 MPa and the wet membrane has the maximum breaking elongation rate of 46.28%. The related experiments indicated that the formation of PECs influence the properties of PEC membranes. The ionic linker of calcium ions and the solvent polarity also can influence the mechanical properties of PEC membranes. The rigidity of PEC membranes can be improved after adding the calcium ions which may be related to the bridge role between the carboxylic groups. Decreasing the solvent polarity can effectively reduce the formation of PEC. In low polarity solution, the chitosan molecular chain curl and reduce the interactions with sodium alginate chains. The stress of PEC membranes reduced with the decreasing solvent polarity.
4. Water absobability, light transmission and water vapor transmission rate ( WVTR ) of chitosan-alginate PEC membranes were important factors for its application. Besides the aspect of material preparation, the application environment also affected the membrane properties because the PEC membrane exhibited pH and ionic strength dependent water uptake in aqueous medium. In low pH or high pH surrounding, the PEC membranes exhibited swelling water uptake. In fact, the wet PEC membranes could be seen as ionic gel. Generally, swelling of ionic gels is driven by osmotic pressure because of the ionic solutes in the gel and in the surrounding solution. The result was possibly related to the decrease of osmotic pressure inside the membrane with increasing of the salt concentration. However, the osmotic pressure difference reached an equivalent value when the concentration of NaCl was 0.2 M and continuously increasing the ionic strength could not significantly change the water absorbability of blank matrix membrane. In order to illuminate the special property of 1:1 composition, we investigated the calcium ions, solvent polarity, composition and stored time factors that may be influence the WVTR of PEC membranes. The chitosan-alginate PEC membranes showed the maximum WVTR value with the 0.01% (w/v) CaCl2 concentration. When the solvent polarity reduce, the macromolecular chains curl and thus lead to increase the space among the chains. For the pure membrane, its WVTR reach to relative high value. However, for the PEC membranes, the WVTR exhibited maximum value at the alginate content of 50% and displayed statistically difference compared with other groups which could be explained that the maximum amount of PEC lead to the pore web structure that facilitate the water vapor traverse. The WVTR of PEC membranes we prepared were from 442 to 618 g/m2/day, which can be regulated by composition. In order to further illustrate the interactions among macromolecular chains, we designed the stored blended solution experiment. The result showed that the WVTR of PEC membrane decrease with the stored time of blended solutionss prolonged. The chitosan-alginate PEC membranes also exhibited excellent light transmission.
5. In the drug release experiments, the cumulative release amount of CA-2 could reach 75% of total amount within 3 days and release rate was also fast when the PEC membrane contain 50% sodium alginate. It is interesting to note that we can not get a more persistent release by increasing the drug loaded amount. When the drug loaded content reach to 15%, the drug diffusion rate decreased significantly, which may be related to the drug diffusion coefficient.
Blended membranes and drug loaded membranes based on chitosan and alginate were prepared by a casting/solvent evaporation method. The structure and properties were evaluated by related techniques and analyse the factors that influence the PECs membrane properties. The process we prepared was moderate and provides the basic data for its application in targeting drug release to special locations in the gastrointestinal tract, bioactive substances controlled carriers, supplement agents, tissue engineering, dialysis, packaging and tablet coating.
本文采用溶剂挥发法制备壳聚糖-海藻酸钠聚电解质复合膜,对铸膜液性质和聚电解质膜有关特性进行研究。利用OM、SEM考察其共混状态和外观形貌,用FTIR和XRD等表征方法对基团键合、结晶情况进行分析,尤其对力学特性、吸水性、吸湿性、透光性等作了较为深入的研究,以磺胺嘧啶银为模型药物考察膜的体外释放行为,并对影响药物释放的有关因素进行分析,以期在壳聚糖-海藻酸钠聚电解质作为药物控释载体的应用方面有所进展。
本文的主要研究内容和结论如下:
1.采用相转化溶剂挥发法,以壳聚糖、海藻酸钠为基材制备壳聚糖-海藻酸钠聚电解质膜。FTIR结果显示,壳聚糖和海藻酸钠在共混后,均发生基团特征吸收峰的位移,表明壳聚糖的功能基团与海藻酸钠的功能基团发生了相互作用。XRD分析结果表明,壳聚糖膜在18.7°和22.5°出有峰值,分别代表水合和脱水晶形,海藻酸钠膜在15.2°和22.5°处有结晶峰。而共混后,这种复合膜显示无规则结构,这种现象可以解释为壳聚糖和海藻酸钠高分子链间的强烈静电相互作用破坏了壳聚糖或海藻酸钠分子形成的规则晶形结构。
2.采用溶液共混的方法,考查溶液粘度性质。在实验中,对于极稀溶液及高浓度壳聚糖和海藻酸钠溶液,在共混过程中,共混溶液均出现黏度最大值,而且用这种溶液铸膜,膜的力学性能及吸水、透气等性能都与溶液粘度性质有关。当海藻酸钠溶液中含有离子交联剂钙离子浓度为0.02%时,溶液显示负触变性。
3.对壳聚糖-海藻酸钠聚电解质膜的力学性能方面进行考查。相关实验结果表明,共混溶液浓度和配比对膜的力学性能有重要影响。对于用极稀溶液配制的聚电解质膜,当海藻酸钠的含量为50%时,共混液的黏度达最大值224cps,铸膜后,干膜有最大断裂强度52.16 MPa,湿膜有最大断裂伸长率为46.28%,综合显示聚电解质复合物的形成对聚电解质膜的性能有重要影响。离子交联剂钙离子的存在以及配制溶液时溶剂的极性都会对聚电解质膜的力学性能产生影响。加入不同浓度的钙离子后,膜的刚性增加,这可能与钙离子在海藻酸钠的羧基之间建立桥连有关。降低溶剂极性能有效降低聚电解质复合物的生成速率。在较低极性的溶液中,壳聚糖分子链成卷曲状,减少了与海藻酸钠分子链的链间相互作用。从结果可以看出,随着溶剂极性的降低,聚电解质膜的力学强度下降,脆性增加。
4.对壳聚糖-海藻酸钠聚电解质膜的吸水、透光/气性、刺激响应方面进行研究。实验结果显示,这种聚电解质膜显示pH响应和离子强度响应的吸水特性,在低pH和高pH外界环境下,聚电解质膜均显示膨胀吸水特性;此聚电解质膜在湿态下可看做离子性凝胶,随着外界溶液离子强度的增大,凝胶膨胀吸水减少,这可能与离子凝胶内外渗透压差减小有关,减少了极性水分子的渗入,而且当NaCl浓度达到0.2M时,基质膜的吸水率不再发生显著变化。为了更清晰说明在两种材料的配比为1:1时生成的聚电解质复合物对聚电解质膜性能的影响,本实验考查了钙离子、溶剂极性、配比和铸膜液放置时间对聚电解质膜的WVTR的影响。结果显示,当钙离子含量为0.01%时,聚电解质膜的水蒸汽透过率最大。这可能与溶剂极性降低后,高分子链蜷曲,减少了高分子链基团间的相互作用,从而增加了高分子链间的孔隙,利于水蒸汽透过,导致聚电解质膜水蒸汽透过率增加有关。对于纯膜,其WVTR均显示较高值,而对于对于复合膜,只有配比为1:1时的复合膜显示较高的WVTR,与其他配比相比,有显著差异(p<0.05),这可能与聚电解质生成量较多,导致更多多孔网状结构,更利于水蒸汽的透过有关。本实验制备的聚电解质膜的WVTR从442至618 g/m2/day,可以通过组分配比调节膜的WVTR。随着铸膜液放置时间的延长,聚电解质膜的WVTR下降,可能是因为对于新鲜配制的铸膜液,两种高聚物中的氨基基团和羧基基团由于空间位阻的作用而没充分接触键合。而在放置过程中,壳聚糖和海藻酸钠的高分子链旋转伸展,有利于未反应的功能基团接触反应。结果是放置一段时间的铸膜液高分子之间相互作用更强,导致形成的聚电解质膜的结构更致密,因此WVTR随着放置时间的延长而显著下降。在透光实验中,壳聚糖膜/海藻酸钠聚电解质膜膜显示具有优良的透光性能。
5.体外药物释放实验中,当海藻酸钠的含量为50%时,药物的累积释放量最大,相同时间内释放的药物最快最多,此时的凝胶具有不溶于水的,有弹性的多孔的网状结构。随着载药量的增加,药物的释放不是同步增加的,载药量为15%时,药物累计释放量反而下降,这可能与药物的扩散系数有关。
本实验采用相转化溶剂挥发法,以壳聚糖、海藻酸钠为基材制备了壳聚糖-海藻酸钠聚电解质膜,并利用不同的测试方法对膜的性能进行测试和评价,对影响聚电解质膜性能的因素进行分析。制备过程简单温和,为其在胃肠道药物释放载体、生物活性物质的控释载体、辅料、组织工程、透析、包装以及包衣等领域的应用提供实验依据。
Due to its special properties, polyelectrolyte complexes ( PEC ) have been given much attention in drug control release areas and have made great progress in stimulating-reaction drug control release, cell immunity-isolation transplant, controlling release of peptide drug, gene therapy and man-made vaccine. In aqueous surroundings, polyasaccharides carrying opposite charges could form PEC. Polybase chitosan and polyacids sodium alginate can form PEC through ionic bonds. This property has been applied in tablet coating, sponge, microsphere and microbeads, but it is difficult to separate from microbeads, microspheres and tablet coating for the site-forming. It is not detailedly expatiated the properties of the membranes formation in present research. In order to solve the problem, we prepared the PEC membranes and investigated its properties using chitosan and sodium alginate.
Membranes of chitosan and alginate were prepared via a casting/solvent evaporation technique. This study investigated the characteristics of blend solutions and drug release properties of PEC membranes. Blendjing states and morphology were observed by OM and SEM. Intermolecular interactions in PEC films have been studied by Fourier transform infrared spectroscopy (FT-IR) and crystal states were measured by XRD. We specially investigated the mechanical characteristics, water-absorbability, moisture absorption, light transmission of the PEC. Aiming at making advanced progress in drug cotrolled carrier, the drug release property was studied by using silver sulfadizine as model drug and the influencing factors were analysed.
The main contents and conclusions are as follows:
1. Blended membranes and drug loaded membranes based on chitosan and alginate were produced by a casting/solvent evaporation method. FTIR results indicated that intermolecular interactions appeared in chitosan-alginate PEC membranes. The chitosan membrane showed two peaks at 18.7°and 22.5°related to the hydrated and anhydrated crystals, respectively. The diffractogram of alginate membrane consisted of two crystalline peaks at 15.2°and 22.5. After complexing, the typical peaks of chitosan disappeared and the PEC showed an amorphous morphology. This can be explained by the strong interactions between chitosan and alginate which had destroyed the close packing of the chitosan or alginate molecules for the formation of regular crystallites.
2. The viscosity properties of blended solutions were analysed. Low-concentration and high concentration of chitosan and alginate blend solution both presented the maximum value in viscosity, which were related to the PEC membranes properties. Sodium alginate with 0.02%w/v CaCl2 exhibited thixotropy-negative.
3. Mechanical properties of chitosan-alginate PEC membranes were tested. Correlated experiments showed that the solution concentration and compostion played important role in mechanical properties. The blended solution viscosity reached the maximum value of 224 cps with 50% w/w sodium alginate concentration. Meanwhile, the dry membrane has maximum breaking stess of 52.16 MPa and the wet membrane has the maximum breaking elongation rate of 46.28%. The related experiments indicated that the formation of PECs influence the properties of PEC membranes. The ionic linker of calcium ions and the solvent polarity also can influence the mechanical properties of PEC membranes. The rigidity of PEC membranes can be improved after adding the calcium ions which may be related to the bridge role between the carboxylic groups. Decreasing the solvent polarity can effectively reduce the formation of PEC. In low polarity solution, the chitosan molecular chain curl and reduce the interactions with sodium alginate chains. The stress of PEC membranes reduced with the decreasing solvent polarity.
4. Water absobability, light transmission and water vapor transmission rate ( WVTR ) of chitosan-alginate PEC membranes were important factors for its application. Besides the aspect of material preparation, the application environment also affected the membrane properties because the PEC membrane exhibited pH and ionic strength dependent water uptake in aqueous medium. In low pH or high pH surrounding, the PEC membranes exhibited swelling water uptake. In fact, the wet PEC membranes could be seen as ionic gel. Generally, swelling of ionic gels is driven by osmotic pressure because of the ionic solutes in the gel and in the surrounding solution. The result was possibly related to the decrease of osmotic pressure inside the membrane with increasing of the salt concentration. However, the osmotic pressure difference reached an equivalent value when the concentration of NaCl was 0.2 M and continuously increasing the ionic strength could not significantly change the water absorbability of blank matrix membrane. In order to illuminate the special property of 1:1 composition, we investigated the calcium ions, solvent polarity, composition and stored time factors that may be influence the WVTR of PEC membranes. The chitosan-alginate PEC membranes showed the maximum WVTR value with the 0.01% (w/v) CaCl2 concentration. When the solvent polarity reduce, the macromolecular chains curl and thus lead to increase the space among the chains. For the pure membrane, its WVTR reach to relative high value. However, for the PEC membranes, the WVTR exhibited maximum value at the alginate content of 50% and displayed statistically difference compared with other groups which could be explained that the maximum amount of PEC lead to the pore web structure that facilitate the water vapor traverse. The WVTR of PEC membranes we prepared were from 442 to 618 g/m2/day, which can be regulated by composition. In order to further illustrate the interactions among macromolecular chains, we designed the stored blended solution experiment. The result showed that the WVTR of PEC membrane decrease with the stored time of blended solutionss prolonged. The chitosan-alginate PEC membranes also exhibited excellent light transmission.
5. In the drug release experiments, the cumulative release amount of CA-2 could reach 75% of total amount within 3 days and release rate was also fast when the PEC membrane contain 50% sodium alginate. It is interesting to note that we can not get a more persistent release by increasing the drug loaded amount. When the drug loaded content reach to 15%, the drug diffusion rate decreased significantly, which may be related to the drug diffusion coefficient.
Blended membranes and drug loaded membranes based on chitosan and alginate were prepared by a casting/solvent evaporation method. The structure and properties were evaluated by related techniques and analyse the factors that influence the PECs membrane properties. The process we prepared was moderate and provides the basic data for its application in targeting drug release to special locations in the gastrointestinal tract, bioactive substances controlled carriers, supplement agents, tissue engineering, dialysis, packaging and tablet coating.
引文
[1] Marguerite Rinaudo. Chitin and chitosan: Properties and applications [J]. Prog. Polym. Sci. 2006, 31: 603-632.
[2]蒋挺大,壳聚糖[M],化学工业出版社,北京. 2001, 3.
[3]姚日生,药用高分子材料[M],化学工业出版社,北京. 2005, 2.
[4] Tozaki H, Odoriba T, Okada N, et al. Chitosan capsules for colon-specific drug delivery: enhanced localization of 5-am-inosalicylic acid in the large intestine accelerates healing of TNBS-induced colitis in rats [J]. J Control Release, 2002, 82(1): 51-61.
[5] Prego C, Torres D, Alonso M J. The potential of chitosan for the oral administration of peptides [J]. Expert. Opin Drug Deliv, 2005, 2: 843-854.
[6] Gungor S, Yildi A, Ozsoy Y, et al. Investigation on mefena-mic acid sustained release tablets with water-insoluble gel [J]. Farmaco. 2003, 58: 397-341.
[7] Khan TA, Peh KK, Ching HS. Mechanical, bioadhesive strength and biological evaluations of chitosan films for wound dressing [J]. J Pharm Pharm Sci. 2000, 3: 303–311.
[8] Dubin PL, Gao J, Mattison K. Protein purification by selective phase separation with polyelectrolytes [J], Sep Puriff Methods, 1994, 23: 1-16.
[9] Shu XZ, Zhu KJ, Song WH. Novel pH-sensitive citrate cross-linked chitosan film for drug controlled release [J]. Int J Pharm. 2001, 212, 19-28.
[10] Denkbas EB, Ozturk E, Ozdemir N, et al. Norflox-axin- loaded chitosan sponges as wound dressing material [J]. Biomater Appl. 2004, 18 (4): 291-303.
[11] Wang L, Khor E, Wee A, et al. Chitosan- alginate PEC membrane as a wound dressing: assessment of incisional wound healing [J]. Biomed Mater Res. 2002, 63 (5): 610-618.
[12] Akihiko K, Minako K, Atsushi W, et al. Effect of Ca2+-alginate gel dissolution on release of dextran with different molecular weights. [J]. J Control Rel. 1999, 58: 21-28.
[13] Chen J, Jo S, Park K. Polysaccharide hydrogels for protein drug delivery, Carbohydr Polym. 1995, 28: 69-76.
[14] Shu XZ, Zhu KJ, Song WH. Novel pH-sensitive citrate cross-linked chitosan film for drug controlled release [J]. Int J Pharm. 2001, 212: 19-28.
[15] Wang SJ, Rhee GJ, Lee KM,et a1.Release characteristics of ibuprofen from exeipient-loaded alginate gel beads [J].Int J Pharm. 1995, 116:125-128.
[16] Takagi I, Shimizu H, Yotsuyanagi T. Application of alginate gel as a vehicle forliposomes I. Factors affecting the loading of drug-containing liposomes and drug release [J]. Chem Pharm Bull, 1996, 44(10):1941-1947.
[17] Orbay H, Unlu RE, Kerem M, et al. Preapplication of lidocaine to split-thickness skin graft donor site to decrease pain during the removal of dressing [J]. Ann Plast Surg. 2006; 56(3): 346-347.
[18]何林,蒋学华,李屯.黏膜给药系统质量评价[J].中国药学杂志, 1998, 33(2):68.
[19]林咸真,郑豪,朱克龙.替硝唑-壳聚糖-海藻酸钠生物复合膜的缓释性能研究[J].浙江大学学报:理学版, 2006, 33(4): 444-446.
[20] S.AL-Musa, Fara DA, Badwan AA. Evaluation of parameters involved in preparation and release of drug loaded in crosslinked matrics of alginate. J Control Rel. 1999, 57: 223-232.
[21] Vasiliu S, Popa M, Rinaudo M. Polyelectrolyte capsules made of two biocompatible natural polymers. Eur Polym J. 2005, 41: 923-932.
[22] Lee KY, Park WH, Ha WS. Polyelectrolyte complexes of sodium alginate with chitosan or its derivatives for microcapsules [J]. J Appl Polym Sci. 1997, 63: 425-432.
[23] Liu LS, Liu SQ, Sy NG, et al. Controlled release of interleukin-2 for tumour immunotherapy using alginate/chitosan porous microspheres [J]. J Control Rel. 1997, 43: 65-74.
[24] Sezer AD, Akbuga J, Release characteristics of chitosan treated alginate beads: I. Sustained release of a macromolecular drug from chitosan treated alginate beads [J], J Microencapsul. 1999, 16, 195-203.
[25]刘群,薛伟明,于炜婷,刘袖洞,严若媛,李金云,马小军.海藻酸钠-壳聚糖微胶囊膜强度的研究[J].高等学校化学学报, 2002, 23(7): 1417-1420.
[26] Gaserod O, Smidsrod O, Skjak-Braek G. Biomaterials [J]. 1998, 19: 18l5-l825.
[27] Polk A, Amsden B, Yao KD, et al. Controlled release of album from chitosan-alginate microcapsules [J]. J Pharm Sci. 1994, 83:178-182.
[28] Hari P R, Chandy T, Sharma C P. Chitosan/calcium-alginate beads for oral delivery of insulin [J]. J Appl Polym Sci. 1996, 59: 795-799.
[29] Charterjee S K,Yadav D.Ghosh S,Khan A M. J polymerSci,Part A.Polymer Chem. 1989, 27: 3855-3856.
[30] Grant GT, Morris ER, Rees DA, Smith PJC, Thom D. Biological interactions between polysaccharides and divalent cations: the egg-box model [J]. FEBS Lett 1973; 32: 195-198.
[31] Tsuchida E. Advance in Po1ym Science. New York Berlin, Heidelberg Springer-Vetlag. 1982.
[32] Bhise KS, Ravindra S, Dhumal et al. Effect of oppositely charged polymer and dissolution medium on swelling, erosion, and drug release from chitosan matrices [J]. AAPS Pharm Sci Tech, 2007; 8 (2): 44.
[33] Sakiyama T, Chia-Hong C, Fujii T, Yano T. Preparation of a polyelectrolyte complex gel from chitosan and kappa-carrageenan and its pH sensitive swelling. J Appl Polym Sci. 1993; 50: 2021-2025.
[34] Monal WA, Hechavarria OL, Rodriguez L, Peniche C. Swelling of membranes from the polyelectrolyte complex between chitosan and carboxymethyl cellulose [J]. Polymer Bulletin, 1993, 31, 471-478.
[35] Visith C, Carlos KS, Torres JA. Formation and characterization of an insoluble polyelectrolyte complex: Chitosan-polyacrylic acid [J]. Polym Bull. 1998, 19, 223-230.
[36] Stoilova O, Koseva N, Manolova N, Rashkov I. Polyelectrolyte complex between chitosan and poly(2-acryloylamido-2-methylpropanesulfonic acid) [J]. Polym Bull. 1999, 43, 67-73.
[37]汪一娟蒋宏亮,胡应乾朱康杰.可生物降解肝素钠/两性壳聚糖复合物用于蛋白药物pH响应释放研究[J].高分子学报, 2005, 4, 524-528.
[38] Muniruzzaman M, Tabata Y, Hijikata S, et al. Structural change of basic fibroblast growth factor through gelatin complexation [J]. Polym Prepr, 1998, 38 (2): 247.
[39] Tabata Y, Hijikata S, Ikada Y. Enhanced vascularization and tissue granulation by basic fibroblast growth factor impegrated in gelatin hydrogels [J]. J Control Rel. 1994, 31:189.
[40] Tabata Y, Yamada K, Miyamoto S, et al. Bone regeneration by basic fibroblast growth factor complexed with biodegradable hydrogels [J]. Biomaterials. 1998, 19: 807-810.
[41] Yamada K, Tabat AY, Yamamoto K, et al. Protential efficacy of basic fibroblast growth factor incorporated in biodegradable hydrogel for skull bone regenerate [J]. J Neurosurg. 1997, 86: 871.
[42] Schroeder-Tefft JA, Bentz H, Estridge TD. Collagen and heparin matrixs for growth factor delivery [J]. J Control Rel. 1997, 48:29.
[43] Mustrafaev M I. Polyelectrolytes in immunology: Iundamental and perspectives [J]. Turk J Chem. 1996, 20: 126-129.
[44] Khaitov RM. Molecular bases for the construction of artificial immunogens and vaccines based on synthetic polyions [J]. Allergy Proc. 1995, 16: 255-258.
[45] George M, Abraham TE. Polyionic hydrocolloids for the intestinal delivery of protein drugs: Alginate and chitosan- a review [J]. J. Control. Rel. 2006, 114: 1–14.
[46] Murata Y, Maeda T, Miyamoto E., Kawashima S, Preparation of chitosan-reinforced alginate gel beads- effects of chitosan on gel matrix erosion [J], Int J Pharm. 1993, 96, 139-145.
[47]朱盛山.药物新剂型[M].北京:化学工业出版社, 2003.
[48] Hurteaux R, Leya FE,Maquin DL, et a1.Coating alginate microspheres with a serum albumin-alginate membrane:application to the encapsulation of a peptide [J]. Eur J Pharm Sci. 2005, 24: 187-197.
[49] Wang SB, Chen AZ, Weng LJ, et al. Effect of the molecular weights of poly-L-arginine on membrane strength and permeability of poly-L-arginine group microcapsules [J]. Macromol Biosci. 2003, 3: 347-350.
[50] Wang SB, Chen AZ, Weng LJ, et al. Effect of drug-loading methods on drug load, encapsulation efficiency and release properties of alginate/poly-L-arginine/chitosan temary complex microcapsules [J]. Macromol Biosci. 2004, 4: 27-30.
[51] Wang SB, Xu FH, He HS, et al.Novel alginate-poly(L-histidine) microcapsules as drug carries: In vitro protein release and short term stability [J]. Macromol Biosci. 2005, 5: 408-414.
[52] Lin WC, Yu DG, Yang MC. pH-sensitive polyelectrolyte complex gel microspheres composed of chitosan/sodium tripolyphosphate/dextran sulfate:swelling kinetics and drug delivery properties [J]. Colloid. Surface.B. 2005, 44: 143-151.
[53] Bhatia SR, Khattakl SF, Roberts SC. Polyelectrolytes for cell encapsulation [J]. Curr Opin Colloid Interface Sci. 2005, 10: 45-51.
[54] Tokifumi M, Tadanao F. Alginate and chitosan polyion complex hybrid fibers for scaffolds in ligament and tendon tissue engineering [J]. J Orthop Sci. 2005, 10: 302-307.
[55] Ott?y MH, Smidsr?d O. Swelling of poly-L-lysine and chitosan-coated superswelling sodium-alginate gel beads [J]. Polym Gels Netw. 1997, 5, 307-314.
[56] Yamane S, Iwasaki N, Majima T, et al. Feasibility of chitosan-based hyaluronic acid hybrid biomaterial for a novel scaffold in cartilage tissue engineering [J]. Biomaterials. 2005, 26: 611-619.
[57] Li Z, Ramay HR, Hauch KD, et al.Xiao D, Zhang M. Chitosan–alginate hybrid scaffolds for bone tissue engineering. Biomaterials. 2005, 26: 3919-3928.
[58] Bouraa C, Menu P, Stoltz JF, et al. Endothelial cells grown on thin polyelectrolyte mutilayered films: an evaluation of a new versatile surface modification [J]. Biomaterials. 2003, 24: 3521-3530.
[59] Etiennea OR, Gasnier C, Egles C, et al. Antifungal coating by biofunctionalized polyelectrolyte multilayered films [J]. Biomaterials. 2005, 26: 6704-6712.
[60] Richert L, Lavalle P, Picart C, et al. Layer by layer buildup of polysaccharide films: physical chemistry and cellular adhesion aspects [J]. Langmuir. 2004, 20: 448-458.
[61] Andreas H, Andreas G, et al. Creating artificial perichondrium by polymer complex membrane macroencapsulation: immune protection and stabilization of subcutaneously transplanted tissue-engineered cartilage [J]. Eur Arch Otorhinolaryngol. 2005, 262: 338-344.
[62]梅兴国主编.生物技术药物制剂-基础与应用[M].北京:化学工业出版社, 2004.
[63] Howard KA, Dash PR, Seymour LW, et al. Infuence of hydrophilicity of cationic polymers on the biophysical properties of polyelectrolyte complexes formed by self- assembly with DNA [J]. Biochimica Biophysica Acta. 2000, 1475: 245-255.
[64] Ren K, Wang Y, Ji J, et al. Construction and deconstruction of PLL/DNA multilayered films for DNA delivery: Effect of ionic strength [J]. Colloid. Surface. B., 2005, 46: 63-69.
[65] Jewel CM, Zhang JT, Lynn DM, et al. Multillayered polyelectrolyte films promote the direct and localized delivery of DNA to cells [J]. J Control Rel. 2005, 106: 214-223.
[66]陈中其,李孝增,鲁成学,化学学报. 1989, 47, 152.
[67] Yamakawa H, Fujii M. Intrinsic viscosity of wormlike chains. Determination of the shift factor [J]. Macromolecules. 1974, 7: 128–135.
[68] Quadrat, O. Adv Colloid Interface Sci. 1985, 24, 45.
[69] Christopoulou V, Papanagopoulos D, Dondos A. Towards abetter mixing of two incompatible polymers by casting from solution without compatibilizer [J]. J Polym Sci B. 1998, 36: 1051-1060.
[70] Dondos A, Christopoulou V, Papanagopoulos D. The influence of the molecular mass of two incompatible polymers on their miscibility in the solid state without compatibilizer after casting from solution [J]. J Polym Sci B. 1999; 37: 379–387.
[71] Christopoulou V, Papanagopoulos D, Dondos A. Relation between the repulsion of incompatible and compatible polymers in solution and their degree of mixing in the solid state: the memory effect [J]. Polym Int. 2000, 49: 1365–1370.
[72] Ogawa K, Yui T, Miya M. Dependence on the preparation procedure of the polymorphism and crystallinity of chitosan membranes [J]. Biosci Biotech Biochem. 1992, 56: 858-862.
[73] Cartier N, Domard A, Chanzy H. Single crystals of chitosan [J]. Int J Biol Macromol. 1990, 12: 289- 294.
[74] Wang LS, Khor E, Lim LY. Chitosan–alginate–CaCl2 system for membrane coat application [J]. J Pharm Sci. 2001, 90: 1134-1142.
[75] Silver FH. Wound dressings and skin replacement. In: Biomaterials, medicaldevices and tissue engineering: An integrated approach. London: Chapman & Hall. 1994, 46-91.
[76] ASTM. Standard test method for water vapor transmission of materials. In: Annual Book of ASTM Standard, vol. 4.06. West Conshohocken, PA: American Society for Testing and Materials. 1995, 697-704.
[77] Hoffman AS. Hydrogels for biomedical applications [J]. Adv Drug Deliv Rev. 2002, 43:3–12.
[78]陈新谦,金有豫,汤光.新编药物学[M].人民卫生出版社,2003: 100-101.
[79] Wright JB, Lam K, Burrell RE, Wound management in an era of increasing bacterial antibiotic resistance: a role for topical silver treatment [J]. Am J Infect Control. 1998, 26, 572-577.
[1] Yang M.-C., Lin W.-C.. The grafting of chitosan oligomerto polysulfone membrane via ozone-treatment and its effect on anti-bacterial activity [J]. J Polym Res, 2002,9: 135~140.
[2] Jennifer elisseeff. Structure starts to gel [J]. Nature materials, 2008, 7: 271~272.
[3] Sakchai Wittaya-areekul, Chureerat Prahsarn, Srisagul Sungthongjeen. Development and in vitro evaluation of chitosan–eudragit RS 30D composite wound dressings [J]. APS Pharm Sci Tech. 2006; 7 (1) Article 30.
[4] Galo Cardenas, Paola Anaya, Carlos von Plessing, Carlos Rojas, Jackeline Sepulveda. Chitosan composite films. Biomedical applications [J]. J Mater Sci: Mater Med, 2008 19: 2397~2405.
[5] Ali Demir Sezer, Fatih Hatipoglu, Erdal Cevher et al. AAPS Pharm Sci Tech 2007; 8 (2) Article 39: E1~E8.
[6] Krishendu Roy, Hai-quan Mao, Shau-ku Huang, Kam W. Leong. Oral gene delivery with chitosan–DNA nanoparticles generates immunologic protection in a murine model of peanut allergy [J]. J Nat Med ,1999, 5 (4) :387~391.
[7]顾汉卿,徐国风.生物医学材料学[M].天津:天津科技翻译出版公司,1993: 318~319.
[8] Kiran S. Bhise, Ravindra S. Dhumal, Bhaskar Chauhan, Anant Paradkar, and Shivajirao S. Kadam. Effect of oppositely charged polymer and dissolution medium on swelling, erosion, and drug release from chitosan matrices [J]. AAPS Pharm. Sci. Tech .2007, 8 (2): E1~E9.
[9]汪剑炜,董炎明,李旭升.甲壳素类液晶高分子的研究Ⅳ.脱乙酰度对壳聚糖液晶性的影响[J].高分子学报, 2000(6): 732~735.
[10] Strand, S. P., T?mmeraas, K., V?rum, K. M., & ?stgaard, K. Electrophoretic light scattering studies of chitosans with different degrees of N-acetylation [J]. Biomacromolecules, 2001, 2, 1310~1314.
[11]贺庆,敖强,修波,公衍道,赵南明,张秀芳. Mechanisms for biocompatibility of chitosan: A new view point [J].中国组织工程研究与临床康复. 2007, 11(35): 7110~7112.
[12] Menemse. In vitro characterization of chitosan scaffolds: influence of composition and deacetylation degree [J]. J Mater Sci: Mater Med, 2007, 18: 1665~1674.
[13] S.Tokura, K.Ueno, S.Miyazaki, N.Nishi, Macromol.Symp. 1997, 120, 1.
[14] Goosen M.F.A.et al. J Mem Sci, 1989, 41: 323~343.
[15]姚子昂,韩宝芹,刘万顺,王文正,玄龙德.不同分子量壳聚糖膜性质的研究[J].中国生物医学工程学报,2002,21(3): 256~262.
[16] Shan-hui Hsu, Shu Wen Whu, Ching-LinTsai, Yuan-HsuanWu, Hui-Wan Chen, Kuo-HuangHsieh. Chitosan as scaffold materials: effects of molecular weight and degree of deacetylation [J]. J Polym Res, 2004, 11: 141~147.
[17] Xiao-Liang Yan, Eugene Khor, Lee Yong Lim. Chitosan-alginate Films prepared with chitosan of different molecular weights [J]. J Biomed Mater Res(Appl Biomater), 2001, 58:358~365.
[18] Thünemann AF, Müller M, Dautzenberg H, Joanny JF, L?wen H. Polyelectrolyte complexes. Advances in Polymer Science, 2004, 166, 113~171.
[19] Lishan Wang, Eugene Khor, Lee Yong Lim. Chitosan-alginate-CaCl2 systemfor membrane coat application [J]. J Pharm Sci, 2001, 90(8): 1134~1142.
[20] Lishan Wang, Eugene Khor, Lee Yong Lim. PEC films prepared from chitosan-alginate coacervates. Chem Pharm Bull, 2000, 48(7): 941~946.
[21]万昌秀.材料的生物学性能及其评价[M].四川大学出版社.2008
[22] Maria Liouni AE Panos Drichoutis AE Elias T. Nerantzis. Studies of the mechanical properties and the fermentation behavior of double layer alginate–chitosan beads, using saccharomyces cerevisiae entrapped cells [J]. World J Microbiol Biotechnol .2008, 24: 281~288.
[23]何保东,石毅等.壳聚糖-海藻酸钠协同相互作用及其凝胶化的研究[J].武汉大学学报. 2002, 48(2): 193~196.
[24] Lishan Wang, Eugene Khor, Aileen Wee, Lee Yong Lim. Chitosan-alginate PEC membrane as a wound dressing: assessment of incisional wound healing [J]. J Biomed Mater Res (Appl Biomater), 2002, 63: 610~618
[25]叶易春,但卫华,曾睿,林海,米贞健,但年华,关林波.胶原与壳聚糖分子间的作用力[J].高分子材料科学与工程.2007, 23(5): 112~115.
[26]梁志红,周长忍,张子勇等.胶原—壳聚糖共混膜的微观结构.应用化学. 2005, 22(4): 451~453.
[27]Zonggang Chen, Xiumei Mo, Chuanglong He, Hongsheng Wang. Intermolecular interactions in electrospun collagen-chitosan complex nanofibers [J]. Carbohydrate Polymers, 2008, 72:410~418.
[28]马建标,王红军,何炳林.壳聚糖与胶原或海藻酸复合物海绵的制备以及人胎儿皮肤成纤维细胞在其中的生长[J].自然科学进展. 2000,10(10): 896~903.
[29] Wei Wang , Shaoqiang Lin , Yechen Xiao , Yadong Huang ,YiTan ,Lu Cai, Xiaokun Li. Acceleration of diabetic wound healing with chitosan-crosslinked collagen sponge containing recombinant human acidic fibroblast growth factor in healing-impaired STZ diabetic rats. Life Sciences [J], 2008, 82: 190~204.
[30]高珊,赵莉,崔磊等.壳聚糖-明胶支架材料的制备及性能研究[J].组织工程与重建外科杂志. 2005, 1(6): 316-319.
[31]赵峰,尹玉姬,宋雪峰,姚康德,郭善一,郭若霖,张镜宇.壳聚糖-明胶网络/羟基磷灰石复合材料支架的研究—制备及形貌[J]. Chinese J Reparative and Reconstructive Surgery, 2001, 15( 5): 276-279.
[2]蒋挺大,壳聚糖[M],化学工业出版社,北京. 2001, 3.
[3]姚日生,药用高分子材料[M],化学工业出版社,北京. 2005, 2.
[4] Tozaki H, Odoriba T, Okada N, et al. Chitosan capsules for colon-specific drug delivery: enhanced localization of 5-am-inosalicylic acid in the large intestine accelerates healing of TNBS-induced colitis in rats [J]. J Control Release, 2002, 82(1): 51-61.
[5] Prego C, Torres D, Alonso M J. The potential of chitosan for the oral administration of peptides [J]. Expert. Opin Drug Deliv, 2005, 2: 843-854.
[6] Gungor S, Yildi A, Ozsoy Y, et al. Investigation on mefena-mic acid sustained release tablets with water-insoluble gel [J]. Farmaco. 2003, 58: 397-341.
[7] Khan TA, Peh KK, Ching HS. Mechanical, bioadhesive strength and biological evaluations of chitosan films for wound dressing [J]. J Pharm Pharm Sci. 2000, 3: 303–311.
[8] Dubin PL, Gao J, Mattison K. Protein purification by selective phase separation with polyelectrolytes [J], Sep Puriff Methods, 1994, 23: 1-16.
[9] Shu XZ, Zhu KJ, Song WH. Novel pH-sensitive citrate cross-linked chitosan film for drug controlled release [J]. Int J Pharm. 2001, 212, 19-28.
[10] Denkbas EB, Ozturk E, Ozdemir N, et al. Norflox-axin- loaded chitosan sponges as wound dressing material [J]. Biomater Appl. 2004, 18 (4): 291-303.
[11] Wang L, Khor E, Wee A, et al. Chitosan- alginate PEC membrane as a wound dressing: assessment of incisional wound healing [J]. Biomed Mater Res. 2002, 63 (5): 610-618.
[12] Akihiko K, Minako K, Atsushi W, et al. Effect of Ca2+-alginate gel dissolution on release of dextran with different molecular weights. [J]. J Control Rel. 1999, 58: 21-28.
[13] Chen J, Jo S, Park K. Polysaccharide hydrogels for protein drug delivery, Carbohydr Polym. 1995, 28: 69-76.
[14] Shu XZ, Zhu KJ, Song WH. Novel pH-sensitive citrate cross-linked chitosan film for drug controlled release [J]. Int J Pharm. 2001, 212: 19-28.
[15] Wang SJ, Rhee GJ, Lee KM,et a1.Release characteristics of ibuprofen from exeipient-loaded alginate gel beads [J].Int J Pharm. 1995, 116:125-128.
[16] Takagi I, Shimizu H, Yotsuyanagi T. Application of alginate gel as a vehicle forliposomes I. Factors affecting the loading of drug-containing liposomes and drug release [J]. Chem Pharm Bull, 1996, 44(10):1941-1947.
[17] Orbay H, Unlu RE, Kerem M, et al. Preapplication of lidocaine to split-thickness skin graft donor site to decrease pain during the removal of dressing [J]. Ann Plast Surg. 2006; 56(3): 346-347.
[18]何林,蒋学华,李屯.黏膜给药系统质量评价[J].中国药学杂志, 1998, 33(2):68.
[19]林咸真,郑豪,朱克龙.替硝唑-壳聚糖-海藻酸钠生物复合膜的缓释性能研究[J].浙江大学学报:理学版, 2006, 33(4): 444-446.
[20] S.AL-Musa, Fara DA, Badwan AA. Evaluation of parameters involved in preparation and release of drug loaded in crosslinked matrics of alginate. J Control Rel. 1999, 57: 223-232.
[21] Vasiliu S, Popa M, Rinaudo M. Polyelectrolyte capsules made of two biocompatible natural polymers. Eur Polym J. 2005, 41: 923-932.
[22] Lee KY, Park WH, Ha WS. Polyelectrolyte complexes of sodium alginate with chitosan or its derivatives for microcapsules [J]. J Appl Polym Sci. 1997, 63: 425-432.
[23] Liu LS, Liu SQ, Sy NG, et al. Controlled release of interleukin-2 for tumour immunotherapy using alginate/chitosan porous microspheres [J]. J Control Rel. 1997, 43: 65-74.
[24] Sezer AD, Akbuga J, Release characteristics of chitosan treated alginate beads: I. Sustained release of a macromolecular drug from chitosan treated alginate beads [J], J Microencapsul. 1999, 16, 195-203.
[25]刘群,薛伟明,于炜婷,刘袖洞,严若媛,李金云,马小军.海藻酸钠-壳聚糖微胶囊膜强度的研究[J].高等学校化学学报, 2002, 23(7): 1417-1420.
[26] Gaserod O, Smidsrod O, Skjak-Braek G. Biomaterials [J]. 1998, 19: 18l5-l825.
[27] Polk A, Amsden B, Yao KD, et al. Controlled release of album from chitosan-alginate microcapsules [J]. J Pharm Sci. 1994, 83:178-182.
[28] Hari P R, Chandy T, Sharma C P. Chitosan/calcium-alginate beads for oral delivery of insulin [J]. J Appl Polym Sci. 1996, 59: 795-799.
[29] Charterjee S K,Yadav D.Ghosh S,Khan A M. J polymerSci,Part A.Polymer Chem. 1989, 27: 3855-3856.
[30] Grant GT, Morris ER, Rees DA, Smith PJC, Thom D. Biological interactions between polysaccharides and divalent cations: the egg-box model [J]. FEBS Lett 1973; 32: 195-198.
[31] Tsuchida E. Advance in Po1ym Science. New York Berlin, Heidelberg Springer-Vetlag. 1982.
[32] Bhise KS, Ravindra S, Dhumal et al. Effect of oppositely charged polymer and dissolution medium on swelling, erosion, and drug release from chitosan matrices [J]. AAPS Pharm Sci Tech, 2007; 8 (2): 44.
[33] Sakiyama T, Chia-Hong C, Fujii T, Yano T. Preparation of a polyelectrolyte complex gel from chitosan and kappa-carrageenan and its pH sensitive swelling. J Appl Polym Sci. 1993; 50: 2021-2025.
[34] Monal WA, Hechavarria OL, Rodriguez L, Peniche C. Swelling of membranes from the polyelectrolyte complex between chitosan and carboxymethyl cellulose [J]. Polymer Bulletin, 1993, 31, 471-478.
[35] Visith C, Carlos KS, Torres JA. Formation and characterization of an insoluble polyelectrolyte complex: Chitosan-polyacrylic acid [J]. Polym Bull. 1998, 19, 223-230.
[36] Stoilova O, Koseva N, Manolova N, Rashkov I. Polyelectrolyte complex between chitosan and poly(2-acryloylamido-2-methylpropanesulfonic acid) [J]. Polym Bull. 1999, 43, 67-73.
[37]汪一娟蒋宏亮,胡应乾朱康杰.可生物降解肝素钠/两性壳聚糖复合物用于蛋白药物pH响应释放研究[J].高分子学报, 2005, 4, 524-528.
[38] Muniruzzaman M, Tabata Y, Hijikata S, et al. Structural change of basic fibroblast growth factor through gelatin complexation [J]. Polym Prepr, 1998, 38 (2): 247.
[39] Tabata Y, Hijikata S, Ikada Y. Enhanced vascularization and tissue granulation by basic fibroblast growth factor impegrated in gelatin hydrogels [J]. J Control Rel. 1994, 31:189.
[40] Tabata Y, Yamada K, Miyamoto S, et al. Bone regeneration by basic fibroblast growth factor complexed with biodegradable hydrogels [J]. Biomaterials. 1998, 19: 807-810.
[41] Yamada K, Tabat AY, Yamamoto K, et al. Protential efficacy of basic fibroblast growth factor incorporated in biodegradable hydrogel for skull bone regenerate [J]. J Neurosurg. 1997, 86: 871.
[42] Schroeder-Tefft JA, Bentz H, Estridge TD. Collagen and heparin matrixs for growth factor delivery [J]. J Control Rel. 1997, 48:29.
[43] Mustrafaev M I. Polyelectrolytes in immunology: Iundamental and perspectives [J]. Turk J Chem. 1996, 20: 126-129.
[44] Khaitov RM. Molecular bases for the construction of artificial immunogens and vaccines based on synthetic polyions [J]. Allergy Proc. 1995, 16: 255-258.
[45] George M, Abraham TE. Polyionic hydrocolloids for the intestinal delivery of protein drugs: Alginate and chitosan- a review [J]. J. Control. Rel. 2006, 114: 1–14.
[46] Murata Y, Maeda T, Miyamoto E., Kawashima S, Preparation of chitosan-reinforced alginate gel beads- effects of chitosan on gel matrix erosion [J], Int J Pharm. 1993, 96, 139-145.
[47]朱盛山.药物新剂型[M].北京:化学工业出版社, 2003.
[48] Hurteaux R, Leya FE,Maquin DL, et a1.Coating alginate microspheres with a serum albumin-alginate membrane:application to the encapsulation of a peptide [J]. Eur J Pharm Sci. 2005, 24: 187-197.
[49] Wang SB, Chen AZ, Weng LJ, et al. Effect of the molecular weights of poly-L-arginine on membrane strength and permeability of poly-L-arginine group microcapsules [J]. Macromol Biosci. 2003, 3: 347-350.
[50] Wang SB, Chen AZ, Weng LJ, et al. Effect of drug-loading methods on drug load, encapsulation efficiency and release properties of alginate/poly-L-arginine/chitosan temary complex microcapsules [J]. Macromol Biosci. 2004, 4: 27-30.
[51] Wang SB, Xu FH, He HS, et al.Novel alginate-poly(L-histidine) microcapsules as drug carries: In vitro protein release and short term stability [J]. Macromol Biosci. 2005, 5: 408-414.
[52] Lin WC, Yu DG, Yang MC. pH-sensitive polyelectrolyte complex gel microspheres composed of chitosan/sodium tripolyphosphate/dextran sulfate:swelling kinetics and drug delivery properties [J]. Colloid. Surface.B. 2005, 44: 143-151.
[53] Bhatia SR, Khattakl SF, Roberts SC. Polyelectrolytes for cell encapsulation [J]. Curr Opin Colloid Interface Sci. 2005, 10: 45-51.
[54] Tokifumi M, Tadanao F. Alginate and chitosan polyion complex hybrid fibers for scaffolds in ligament and tendon tissue engineering [J]. J Orthop Sci. 2005, 10: 302-307.
[55] Ott?y MH, Smidsr?d O. Swelling of poly-L-lysine and chitosan-coated superswelling sodium-alginate gel beads [J]. Polym Gels Netw. 1997, 5, 307-314.
[56] Yamane S, Iwasaki N, Majima T, et al. Feasibility of chitosan-based hyaluronic acid hybrid biomaterial for a novel scaffold in cartilage tissue engineering [J]. Biomaterials. 2005, 26: 611-619.
[57] Li Z, Ramay HR, Hauch KD, et al.Xiao D, Zhang M. Chitosan–alginate hybrid scaffolds for bone tissue engineering. Biomaterials. 2005, 26: 3919-3928.
[58] Bouraa C, Menu P, Stoltz JF, et al. Endothelial cells grown on thin polyelectrolyte mutilayered films: an evaluation of a new versatile surface modification [J]. Biomaterials. 2003, 24: 3521-3530.
[59] Etiennea OR, Gasnier C, Egles C, et al. Antifungal coating by biofunctionalized polyelectrolyte multilayered films [J]. Biomaterials. 2005, 26: 6704-6712.
[60] Richert L, Lavalle P, Picart C, et al. Layer by layer buildup of polysaccharide films: physical chemistry and cellular adhesion aspects [J]. Langmuir. 2004, 20: 448-458.
[61] Andreas H, Andreas G, et al. Creating artificial perichondrium by polymer complex membrane macroencapsulation: immune protection and stabilization of subcutaneously transplanted tissue-engineered cartilage [J]. Eur Arch Otorhinolaryngol. 2005, 262: 338-344.
[62]梅兴国主编.生物技术药物制剂-基础与应用[M].北京:化学工业出版社, 2004.
[63] Howard KA, Dash PR, Seymour LW, et al. Infuence of hydrophilicity of cationic polymers on the biophysical properties of polyelectrolyte complexes formed by self- assembly with DNA [J]. Biochimica Biophysica Acta. 2000, 1475: 245-255.
[64] Ren K, Wang Y, Ji J, et al. Construction and deconstruction of PLL/DNA multilayered films for DNA delivery: Effect of ionic strength [J]. Colloid. Surface. B., 2005, 46: 63-69.
[65] Jewel CM, Zhang JT, Lynn DM, et al. Multillayered polyelectrolyte films promote the direct and localized delivery of DNA to cells [J]. J Control Rel. 2005, 106: 214-223.
[66]陈中其,李孝增,鲁成学,化学学报. 1989, 47, 152.
[67] Yamakawa H, Fujii M. Intrinsic viscosity of wormlike chains. Determination of the shift factor [J]. Macromolecules. 1974, 7: 128–135.
[68] Quadrat, O. Adv Colloid Interface Sci. 1985, 24, 45.
[69] Christopoulou V, Papanagopoulos D, Dondos A. Towards abetter mixing of two incompatible polymers by casting from solution without compatibilizer [J]. J Polym Sci B. 1998, 36: 1051-1060.
[70] Dondos A, Christopoulou V, Papanagopoulos D. The influence of the molecular mass of two incompatible polymers on their miscibility in the solid state without compatibilizer after casting from solution [J]. J Polym Sci B. 1999; 37: 379–387.
[71] Christopoulou V, Papanagopoulos D, Dondos A. Relation between the repulsion of incompatible and compatible polymers in solution and their degree of mixing in the solid state: the memory effect [J]. Polym Int. 2000, 49: 1365–1370.
[72] Ogawa K, Yui T, Miya M. Dependence on the preparation procedure of the polymorphism and crystallinity of chitosan membranes [J]. Biosci Biotech Biochem. 1992, 56: 858-862.
[73] Cartier N, Domard A, Chanzy H. Single crystals of chitosan [J]. Int J Biol Macromol. 1990, 12: 289- 294.
[74] Wang LS, Khor E, Lim LY. Chitosan–alginate–CaCl2 system for membrane coat application [J]. J Pharm Sci. 2001, 90: 1134-1142.
[75] Silver FH. Wound dressings and skin replacement. In: Biomaterials, medicaldevices and tissue engineering: An integrated approach. London: Chapman & Hall. 1994, 46-91.
[76] ASTM. Standard test method for water vapor transmission of materials. In: Annual Book of ASTM Standard, vol. 4.06. West Conshohocken, PA: American Society for Testing and Materials. 1995, 697-704.
[77] Hoffman AS. Hydrogels for biomedical applications [J]. Adv Drug Deliv Rev. 2002, 43:3–12.
[78]陈新谦,金有豫,汤光.新编药物学[M].人民卫生出版社,2003: 100-101.
[79] Wright JB, Lam K, Burrell RE, Wound management in an era of increasing bacterial antibiotic resistance: a role for topical silver treatment [J]. Am J Infect Control. 1998, 26, 572-577.
[1] Yang M.-C., Lin W.-C.. The grafting of chitosan oligomerto polysulfone membrane via ozone-treatment and its effect on anti-bacterial activity [J]. J Polym Res, 2002,9: 135~140.
[2] Jennifer elisseeff. Structure starts to gel [J]. Nature materials, 2008, 7: 271~272.
[3] Sakchai Wittaya-areekul, Chureerat Prahsarn, Srisagul Sungthongjeen. Development and in vitro evaluation of chitosan–eudragit RS 30D composite wound dressings [J]. APS Pharm Sci Tech. 2006; 7 (1) Article 30.
[4] Galo Cardenas, Paola Anaya, Carlos von Plessing, Carlos Rojas, Jackeline Sepulveda. Chitosan composite films. Biomedical applications [J]. J Mater Sci: Mater Med, 2008 19: 2397~2405.
[5] Ali Demir Sezer, Fatih Hatipoglu, Erdal Cevher et al. AAPS Pharm Sci Tech 2007; 8 (2) Article 39: E1~E8.
[6] Krishendu Roy, Hai-quan Mao, Shau-ku Huang, Kam W. Leong. Oral gene delivery with chitosan–DNA nanoparticles generates immunologic protection in a murine model of peanut allergy [J]. J Nat Med ,1999, 5 (4) :387~391.
[7]顾汉卿,徐国风.生物医学材料学[M].天津:天津科技翻译出版公司,1993: 318~319.
[8] Kiran S. Bhise, Ravindra S. Dhumal, Bhaskar Chauhan, Anant Paradkar, and Shivajirao S. Kadam. Effect of oppositely charged polymer and dissolution medium on swelling, erosion, and drug release from chitosan matrices [J]. AAPS Pharm. Sci. Tech .2007, 8 (2): E1~E9.
[9]汪剑炜,董炎明,李旭升.甲壳素类液晶高分子的研究Ⅳ.脱乙酰度对壳聚糖液晶性的影响[J].高分子学报, 2000(6): 732~735.
[10] Strand, S. P., T?mmeraas, K., V?rum, K. M., & ?stgaard, K. Electrophoretic light scattering studies of chitosans with different degrees of N-acetylation [J]. Biomacromolecules, 2001, 2, 1310~1314.
[11]贺庆,敖强,修波,公衍道,赵南明,张秀芳. Mechanisms for biocompatibility of chitosan: A new view point [J].中国组织工程研究与临床康复. 2007, 11(35): 7110~7112.
[12] Menemse. In vitro characterization of chitosan scaffolds: influence of composition and deacetylation degree [J]. J Mater Sci: Mater Med, 2007, 18: 1665~1674.
[13] S.Tokura, K.Ueno, S.Miyazaki, N.Nishi, Macromol.Symp. 1997, 120, 1.
[14] Goosen M.F.A.et al. J Mem Sci, 1989, 41: 323~343.
[15]姚子昂,韩宝芹,刘万顺,王文正,玄龙德.不同分子量壳聚糖膜性质的研究[J].中国生物医学工程学报,2002,21(3): 256~262.
[16] Shan-hui Hsu, Shu Wen Whu, Ching-LinTsai, Yuan-HsuanWu, Hui-Wan Chen, Kuo-HuangHsieh. Chitosan as scaffold materials: effects of molecular weight and degree of deacetylation [J]. J Polym Res, 2004, 11: 141~147.
[17] Xiao-Liang Yan, Eugene Khor, Lee Yong Lim. Chitosan-alginate Films prepared with chitosan of different molecular weights [J]. J Biomed Mater Res(Appl Biomater), 2001, 58:358~365.
[18] Thünemann AF, Müller M, Dautzenberg H, Joanny JF, L?wen H. Polyelectrolyte complexes. Advances in Polymer Science, 2004, 166, 113~171.
[19] Lishan Wang, Eugene Khor, Lee Yong Lim. Chitosan-alginate-CaCl2 systemfor membrane coat application [J]. J Pharm Sci, 2001, 90(8): 1134~1142.
[20] Lishan Wang, Eugene Khor, Lee Yong Lim. PEC films prepared from chitosan-alginate coacervates. Chem Pharm Bull, 2000, 48(7): 941~946.
[21]万昌秀.材料的生物学性能及其评价[M].四川大学出版社.2008
[22] Maria Liouni AE Panos Drichoutis AE Elias T. Nerantzis. Studies of the mechanical properties and the fermentation behavior of double layer alginate–chitosan beads, using saccharomyces cerevisiae entrapped cells [J]. World J Microbiol Biotechnol .2008, 24: 281~288.
[23]何保东,石毅等.壳聚糖-海藻酸钠协同相互作用及其凝胶化的研究[J].武汉大学学报. 2002, 48(2): 193~196.
[24] Lishan Wang, Eugene Khor, Aileen Wee, Lee Yong Lim. Chitosan-alginate PEC membrane as a wound dressing: assessment of incisional wound healing [J]. J Biomed Mater Res (Appl Biomater), 2002, 63: 610~618
[25]叶易春,但卫华,曾睿,林海,米贞健,但年华,关林波.胶原与壳聚糖分子间的作用力[J].高分子材料科学与工程.2007, 23(5): 112~115.
[26]梁志红,周长忍,张子勇等.胶原—壳聚糖共混膜的微观结构.应用化学. 2005, 22(4): 451~453.
[27]Zonggang Chen, Xiumei Mo, Chuanglong He, Hongsheng Wang. Intermolecular interactions in electrospun collagen-chitosan complex nanofibers [J]. Carbohydrate Polymers, 2008, 72:410~418.
[28]马建标,王红军,何炳林.壳聚糖与胶原或海藻酸复合物海绵的制备以及人胎儿皮肤成纤维细胞在其中的生长[J].自然科学进展. 2000,10(10): 896~903.
[29] Wei Wang , Shaoqiang Lin , Yechen Xiao , Yadong Huang ,YiTan ,Lu Cai, Xiaokun Li. Acceleration of diabetic wound healing with chitosan-crosslinked collagen sponge containing recombinant human acidic fibroblast growth factor in healing-impaired STZ diabetic rats. Life Sciences [J], 2008, 82: 190~204.
[30]高珊,赵莉,崔磊等.壳聚糖-明胶支架材料的制备及性能研究[J].组织工程与重建外科杂志. 2005, 1(6): 316-319.
[31]赵峰,尹玉姬,宋雪峰,姚康德,郭善一,郭若霖,张镜宇.壳聚糖-明胶网络/羟基磷灰石复合材料支架的研究—制备及形貌[J]. Chinese J Reparative and Reconstructive Surgery, 2001, 15( 5): 276-279.