壳聚糖油酸复合物纳米微球的制备及性能
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摘要
纳米药物具有能够改善药物的溶解速率,增强药物的靶向性、缓释性、可控性,低毒性及智能性等性质。壳聚糖具有良好的生物相容性和生物可降解性,近年来在药物制剂中的应用越来越广泛,壳聚糖基纳米微粒是一类极具应用前景的药物控释载体。本文建立了一种壳聚糖油酸复合物纳米微球体系,对这种体系进行了特性分析,并对纳米微球的制备工艺进行了进一步探讨。
本论文制备了油酰壳聚糖复合物(OCS),并检测了OCS的物理化学性质。利用OCS制备出纳米微球,分析了该纳米微球对成纤维细胞及血液细胞的细胞毒性、体内分布情况以及透粘膜特性。选用阿霉素和利福平做模型药物,检测了OCS纳米微球对药物的控释情况。在OCS疏水修饰的基础上通过羧甲基化、季铵盐化以及降解得到壳寡糖的办法制备了水溶性的两亲衍生物,并制备出纳米微粒。制备了OCS包被的聚丙酸-乙醇酸(PLGA)纳米微球。
利用EDC介导反应及壳聚糖和油酰氯反应的办法合成OCS,红外光谱、紫外光谱及核磁共振谱检测证明了产物的结构。OCS溶解性比壳聚糖差,但是溶解性随pH变化的趋势和壳聚糖一样;随着OCS取代度的增高溶解性降低;随着OCS分子量的增大溶解性降低。所制备的OCS具有降低表面张力的能力;随着取代度的增高和分子量的降低,这种降低表面张力的能力逐渐增强。OCS在溶液中具有较高的粘度,粘度高于壳聚糖,且粘度随着取代度的增大和分子量的增大而增强。OCS在盐酸中的粘度比在乙酸中低;温度增高OCS粘度降低。OCS具有一定的吸湿性,但是吸湿性比壳聚糖差,油酸基的引入打破了壳聚糖分子原来的排列,并且占据了部分氨基的位点,氨基数量的减少使氢键的减少,因此OCS吸湿性比壳聚糖差。
通过荧光探针实验、激光球度散射仪、透射电镜观察检测了OCS纳米微球的成球性质。结果表明随着浓度增大,取代度的增大,OCS分子量的降低成球趋势愈加明显。取代度5%、11%、27%的三个样品临界聚集浓度(CAC)值分别是79.43mg/L、31.6mg/L和10mg/L。分子量的增大不利于微球形成,分子量越大,CAC值越大。CH2Cl2的加入有利于OCS溶液中疏水微区的形成。利用乳化均质法处理OCS可以形成纳米微球,所制备的纳米微球呈圆形,形态完整。取代度5%和11%的两个样品所形成的纳米微球的粒径分别是327.4nm和275.3nm;随着OCS取代度增大球粒径降低,因为在高取代度溶液中能形成更紧密地疏水内核。分子量的增大不利于纳米微球的形成,高分子量的样品不能形成纳米微球。
红外光谱显示利福平已经成功的负载到OCS纳米微球上。随着取代度的增大微球对利福平包封率和载药量逐渐增高;随着分子量的降低微球对利福平包封率和载药量升高。OCS纳米微球具有一定的缓释效果,取代度的增大和分子量的提高可以增强缓释效果。利福平在pH6.0和pH6.8的释放介质中的释放没有明显差异,在pH3.8的介质中释放要比上面两个条件下慢。TPP的加入可以明显减慢利福平的释放。高利福平浓度的样品释放的比较缓慢,药物平衡释放分数较小。红外结果显示阿霉素已经成功的负载到OCS纳米微球上。阿霉素在三个不同取代度的OCS样品中的释放速率和平衡释放分数相差不大;阿霉素在高分子量的OCS样品中具有较好的缓释效果和较高的平衡释放分数。阿霉素在pH3.8的醋酸缓冲液中比在pH6.8的PBS中具有较高的平衡释放分数。投药量对阿霉素的缓释影响不大。OCS浓度的增大可以降低阿霉素释放速率。交联剂TPP的加入对阿霉素释放影响不大。
溶血实验表面直接接触时各个OCS样品对红细胞可被看作是无毒的;然而溶液实验以及纳米微球的结果却显示这些OCS复合物在溶液状态下对红细胞的毒性作用是不容忽视的。大部分OCS样品在作用浓度为0.1%时溶血率均低于10%,符合与血液接触应用以及适用于静脉注射的较宽泛标准。细胞毒性实验显示壳聚糖、OCS及OCS纳米微球对胎鼠皮肤成纤维细胞均未表现出明显的细胞毒性。OCS的细胞毒性略大于壳聚糖,但是所形成的OCS纳米微球对细胞毒性比壳聚糖低。体内分布实验表明纳米微球在心脏和肝脏内基本上没有;肺部分布得较多,在肺部的微球浓度随时间逐渐降低;在血液中的微球浓度随时间降低;肾脏中的微球浓度逐渐增大。透粘膜实验表面OCS和不同取代度的纳米微球对粘膜具有较好的透过性。纳米微球对胃粘膜的吸附性优于OCS溶液;但是对肠粘膜的透过吸附性显著差于溶液。取代度5%的样品对胃粘膜的吸附能力高于2%样品;而对肠粘膜的吸附能力差于2%的样品。
通过羧甲基化、季铵盐化和H2O2降解的办法制备水溶性的双亲OCS衍生物。红外结果显示我们已经成功的制备了羧甲基油酰壳聚糖(OCMCS)、油酰壳聚糖季铵盐(OQCS)和油酰壳寡糖(OCSO)。所制备的OCMCS和OQCS相对壳聚糖和OCS具有更好的溶解性,在中性条件下可以溶解;OCSO在中性条件下能够很好的溶胀。三种材料都具有良好的吸湿性和生物相容性。采用O/W乳化法制备了纳米微球,透射电镜结果显示纳米微球形状完整,粒径分析结果显示大小均为200nm左右。用这种方法成功制备出了在中性条件下的纳米微球,拓宽了我们之前制备的OCS纳米微球的应用范围。
通过乳化法制备了OCS包被的PLGA纳米微球,并检测了制备过程中各个因素对成球率、微球稳定性和微球形态的影响。随着PLGA加入量增多,纳米微球成球率先增大后减小;提高OCS浓度使成球率降低;成球率随着CH2Cl2加入量的增多而上升;提高均质速率使成球率上升。提高PLGA的量有利于纳米微球核心的形成;加大OCS的浓度有利于纳米微球的形成;加大CH2Cl2的加入量有利于纳米微球的形成。所制备的纳米微球具有较好的形态和稳定性,原子力显微镜和透射电镜结果显示样品纳米微球的粒径200nm左右,微球形态圆形,大小均一。
所制备的壳聚糖油酸复合物纳米微球具有较好的形态和稳定性,壳聚糖油酸复合物是一种非常好的可用作载药微球制备的材料。
Chitosan is inexpensive, non-toxic, hydrophilic, biocompatible and biodegradable and has been used as medical materials for drug delivery systems. A new oleoylchitosan compound nanoparticles system is prepared and the characteristics are evaluated.
Oleoyl-chitosan (OCS) is synthesized and examined. OCS nanoparticles are prepared using an O/W emulsification method. Cytotoxicity of OCS is investigated via the red blood cell lysis test and the MTT assay. Rifampicin and doxorubicin, as model drug, are investigated for release properties in vitro. Oleoyl-carboxymethyl chitosan (OCMCS), oleoyl-quaternized chitosan (OQCS), oleoyl-chitosan oligosaccharide (OCSO) are synthesized to improve the solubility of OCS. The PLGA-OCS nanoparticle is prepared using PLGA as hydrophobic core to improve the stability of OCS nanoparticles.
OCS with different molecular weight (MW) and degrees of substitution (DS) are synthesized by reacting chitosan with oleoyl chloride. The FT-IR, UV, and 1H NMR suggest the formation of an amide linkage between amino groups of chitosan and carboxyl groups of oleic acid. These OCS exhibited poor solubility in aqueous acidic solution. The solubility of OCS decreases as the increase of DS and MW. These OCS are not soluble at neutral or alkali pH. All the OCS samples can reduce the surfacee tension slightly. The increase of DS values and decrease of MW can increase the ability of OCS. The viscosity of OCS sharply increases with the increase of concentration, whereas that of unmodified chitosan rises only slightly. This increase is stronger as the increase of DS and MW of the polymer. The viscosity of OCS in HCl is larger than in HAc. The viscosity decreases with the increase of temperature. The hydration property of OCS is good. The hydration property of OCS is lower than CS. As for OCS, some of–NH2 are occupied by oleoyl groups, which decreases the numbers of–NH2 and also the hydrogen bonds between hydrophilic groups and water.
The self-assembling properties of OCS are analyzed using the fluorescence probe test, the laser light scattering and the transmission electron microscopy. The results show that OCS molecules tend to assemble when the concentration is higher than about 0.1g/l and this trend increases with the rise of concentration. This tend is stronger as the increase of DS and decrease of MW of OCS. The critical aggregation concentration (CAC) of OCS with DS 5, 11, and 27% are 79.43, 31.6, 10 mg/L, respectively, and the CAC of samples with molecular masses of 20, 38, 300, and 1100 kDa are 50.1, 79.43, 125.9, and 630.9 mg/L, respectively. The addition of CH2Cl2 helps to the formation of nanoparticles. Nanoparticles were prepared using O/W emulsification method. Most of the nanoparticles formed are around 200nm and are of a spherical shape, which indicates that the prepared nanoparticles have good structural integrity. The size of self-aggregates decreased as the DS increased, indicating formation of denser hydrophobic cores in high DS sample. Mean diameter of the polymeric amphiphilic nanoparticles of OCS with DS 5% and 11% were around 327.4 nm and 275.3 nm. The increase of DS and decrease of MW might facilitate the formation of nanoparticles but the DS should be not too large to have a compromise between solubility and viscosity.
Rifampicin and doxorubicin, as model drug, are investigated for their release properties in vitro. The FTIR of rifampicin loaded OCS nanoparticles indicate the success of model drug rifampicin to OCS nanoparticles. The loading efficiency increases as the increase of DS and the decrease of MW. The release of rifampicin slower as the DS and MW increased. The release of rifampicin from solution with pH 6.0 and 6.8 was characterized by a faster release than from solution with pH 3.8. The increase of TPP can slow the release of drug. The sample with low concentration of rifampicin release faster and entirely. The FTIR of doxorubicin loaded OCS nanoparticles indicate the success of model drug doxorubicin to OCS nanoparticles. The release speed of doxorubicin of three DS OCS sample is similar. The increase of MW of OCS can slow the release of doxorubicin. The release of doxorubicin is slower in pH 3.8 HAc than in pH 6.8 PBS. The effect of doxorubicin and TPP concentration on release is unconspicuous. The increase of OCS concentration can slow the release of doxorubicin.
Cytotoxicity of OCS is investigated via the red blood cell lysis test and the MTT assay. The red blood cell lysis test shows that each sample can be regarded as non-toxic to red blood cells in the solid state, while the cytotoxicity can not be neglected in the solution state and nanoparticles state. The hemolysis rate of most OCS samples is less than 10% which was regarded as non-toxic effect level. OCS exhibits no cytotoxicity to fetal mouse skin fibroblast with the increase of concentration. All the OCS and OCS nanoparticles have good biocompatibility from the cytotoxicity testing. And the biocompatibility of OCS nanoparticles was better than OCS solution. The toxic effect of nanoparticles in the acidic medium may be due to the fully protonation of the primary amino groups. The biodistribution test of OCS nanoparticles suggests the accumulation in spleen and lung. The mucosa test suggests the OCS can adhere and across the stomach and intestine mucosa. The adherence of OCS nanoparticles onto stomach mucosa is stronger than OCS solution,while that onto intestine mucosa is less than OCS solution.
Oleoyl-carboxymethyl chitosan (OCMCS), Oleoyl-quaternized chitosan (OQCS), oleoyl-chitosan oligosaccharide (OCSO) are synthesized to impvove the solubility of OCS. The results of FTIR confirm the successful modification. The solubility of OCMCS, OQCS, and OCSO are better than OCS. Three kinds of chitosan derivatives have good biocompatibility and hydration property. Nanoparticles of OCMCS, OQCS and OCSO are prepared using an O/W emulsification method. The TEM conformed nanoparticles have good structural integrity.
The PLGA-OCS nanoparticles are prepared using PLGA as hydrophobic core. The effect of PLGA content, OCS concentration, emulsification speed, and H2Cl2 content on the formation of nanoparticles is invisigated. The PLGA content affect the foamation efficiency of slightly. The increase of OCS concentration can decrease the foamation efficiency. The increase of CH2Cl2 concentration can increase the foamation efficiency. The inceease of emulsification speed can increase the foamation efficiency. The increase of emulsification speed can redound to the formation. The incerese of PLGA content, OCS concentration, and CH2Cl2 concentration can redound to the formation of nanoparticles. The Most of the nanoparticles formed are around 200nm and are of a spherical shape.
Oleoylchitosan compound nanoparticles had good biocompability and characteristics which could be the ideal delivery systems of active biomaterials.
本论文制备了油酰壳聚糖复合物(OCS),并检测了OCS的物理化学性质。利用OCS制备出纳米微球,分析了该纳米微球对成纤维细胞及血液细胞的细胞毒性、体内分布情况以及透粘膜特性。选用阿霉素和利福平做模型药物,检测了OCS纳米微球对药物的控释情况。在OCS疏水修饰的基础上通过羧甲基化、季铵盐化以及降解得到壳寡糖的办法制备了水溶性的两亲衍生物,并制备出纳米微粒。制备了OCS包被的聚丙酸-乙醇酸(PLGA)纳米微球。
利用EDC介导反应及壳聚糖和油酰氯反应的办法合成OCS,红外光谱、紫外光谱及核磁共振谱检测证明了产物的结构。OCS溶解性比壳聚糖差,但是溶解性随pH变化的趋势和壳聚糖一样;随着OCS取代度的增高溶解性降低;随着OCS分子量的增大溶解性降低。所制备的OCS具有降低表面张力的能力;随着取代度的增高和分子量的降低,这种降低表面张力的能力逐渐增强。OCS在溶液中具有较高的粘度,粘度高于壳聚糖,且粘度随着取代度的增大和分子量的增大而增强。OCS在盐酸中的粘度比在乙酸中低;温度增高OCS粘度降低。OCS具有一定的吸湿性,但是吸湿性比壳聚糖差,油酸基的引入打破了壳聚糖分子原来的排列,并且占据了部分氨基的位点,氨基数量的减少使氢键的减少,因此OCS吸湿性比壳聚糖差。
通过荧光探针实验、激光球度散射仪、透射电镜观察检测了OCS纳米微球的成球性质。结果表明随着浓度增大,取代度的增大,OCS分子量的降低成球趋势愈加明显。取代度5%、11%、27%的三个样品临界聚集浓度(CAC)值分别是79.43mg/L、31.6mg/L和10mg/L。分子量的增大不利于微球形成,分子量越大,CAC值越大。CH2Cl2的加入有利于OCS溶液中疏水微区的形成。利用乳化均质法处理OCS可以形成纳米微球,所制备的纳米微球呈圆形,形态完整。取代度5%和11%的两个样品所形成的纳米微球的粒径分别是327.4nm和275.3nm;随着OCS取代度增大球粒径降低,因为在高取代度溶液中能形成更紧密地疏水内核。分子量的增大不利于纳米微球的形成,高分子量的样品不能形成纳米微球。
红外光谱显示利福平已经成功的负载到OCS纳米微球上。随着取代度的增大微球对利福平包封率和载药量逐渐增高;随着分子量的降低微球对利福平包封率和载药量升高。OCS纳米微球具有一定的缓释效果,取代度的增大和分子量的提高可以增强缓释效果。利福平在pH6.0和pH6.8的释放介质中的释放没有明显差异,在pH3.8的介质中释放要比上面两个条件下慢。TPP的加入可以明显减慢利福平的释放。高利福平浓度的样品释放的比较缓慢,药物平衡释放分数较小。红外结果显示阿霉素已经成功的负载到OCS纳米微球上。阿霉素在三个不同取代度的OCS样品中的释放速率和平衡释放分数相差不大;阿霉素在高分子量的OCS样品中具有较好的缓释效果和较高的平衡释放分数。阿霉素在pH3.8的醋酸缓冲液中比在pH6.8的PBS中具有较高的平衡释放分数。投药量对阿霉素的缓释影响不大。OCS浓度的增大可以降低阿霉素释放速率。交联剂TPP的加入对阿霉素释放影响不大。
溶血实验表面直接接触时各个OCS样品对红细胞可被看作是无毒的;然而溶液实验以及纳米微球的结果却显示这些OCS复合物在溶液状态下对红细胞的毒性作用是不容忽视的。大部分OCS样品在作用浓度为0.1%时溶血率均低于10%,符合与血液接触应用以及适用于静脉注射的较宽泛标准。细胞毒性实验显示壳聚糖、OCS及OCS纳米微球对胎鼠皮肤成纤维细胞均未表现出明显的细胞毒性。OCS的细胞毒性略大于壳聚糖,但是所形成的OCS纳米微球对细胞毒性比壳聚糖低。体内分布实验表明纳米微球在心脏和肝脏内基本上没有;肺部分布得较多,在肺部的微球浓度随时间逐渐降低;在血液中的微球浓度随时间降低;肾脏中的微球浓度逐渐增大。透粘膜实验表面OCS和不同取代度的纳米微球对粘膜具有较好的透过性。纳米微球对胃粘膜的吸附性优于OCS溶液;但是对肠粘膜的透过吸附性显著差于溶液。取代度5%的样品对胃粘膜的吸附能力高于2%样品;而对肠粘膜的吸附能力差于2%的样品。
通过羧甲基化、季铵盐化和H2O2降解的办法制备水溶性的双亲OCS衍生物。红外结果显示我们已经成功的制备了羧甲基油酰壳聚糖(OCMCS)、油酰壳聚糖季铵盐(OQCS)和油酰壳寡糖(OCSO)。所制备的OCMCS和OQCS相对壳聚糖和OCS具有更好的溶解性,在中性条件下可以溶解;OCSO在中性条件下能够很好的溶胀。三种材料都具有良好的吸湿性和生物相容性。采用O/W乳化法制备了纳米微球,透射电镜结果显示纳米微球形状完整,粒径分析结果显示大小均为200nm左右。用这种方法成功制备出了在中性条件下的纳米微球,拓宽了我们之前制备的OCS纳米微球的应用范围。
通过乳化法制备了OCS包被的PLGA纳米微球,并检测了制备过程中各个因素对成球率、微球稳定性和微球形态的影响。随着PLGA加入量增多,纳米微球成球率先增大后减小;提高OCS浓度使成球率降低;成球率随着CH2Cl2加入量的增多而上升;提高均质速率使成球率上升。提高PLGA的量有利于纳米微球核心的形成;加大OCS的浓度有利于纳米微球的形成;加大CH2Cl2的加入量有利于纳米微球的形成。所制备的纳米微球具有较好的形态和稳定性,原子力显微镜和透射电镜结果显示样品纳米微球的粒径200nm左右,微球形态圆形,大小均一。
所制备的壳聚糖油酸复合物纳米微球具有较好的形态和稳定性,壳聚糖油酸复合物是一种非常好的可用作载药微球制备的材料。
Chitosan is inexpensive, non-toxic, hydrophilic, biocompatible and biodegradable and has been used as medical materials for drug delivery systems. A new oleoylchitosan compound nanoparticles system is prepared and the characteristics are evaluated.
Oleoyl-chitosan (OCS) is synthesized and examined. OCS nanoparticles are prepared using an O/W emulsification method. Cytotoxicity of OCS is investigated via the red blood cell lysis test and the MTT assay. Rifampicin and doxorubicin, as model drug, are investigated for release properties in vitro. Oleoyl-carboxymethyl chitosan (OCMCS), oleoyl-quaternized chitosan (OQCS), oleoyl-chitosan oligosaccharide (OCSO) are synthesized to improve the solubility of OCS. The PLGA-OCS nanoparticle is prepared using PLGA as hydrophobic core to improve the stability of OCS nanoparticles.
OCS with different molecular weight (MW) and degrees of substitution (DS) are synthesized by reacting chitosan with oleoyl chloride. The FT-IR, UV, and 1H NMR suggest the formation of an amide linkage between amino groups of chitosan and carboxyl groups of oleic acid. These OCS exhibited poor solubility in aqueous acidic solution. The solubility of OCS decreases as the increase of DS and MW. These OCS are not soluble at neutral or alkali pH. All the OCS samples can reduce the surfacee tension slightly. The increase of DS values and decrease of MW can increase the ability of OCS. The viscosity of OCS sharply increases with the increase of concentration, whereas that of unmodified chitosan rises only slightly. This increase is stronger as the increase of DS and MW of the polymer. The viscosity of OCS in HCl is larger than in HAc. The viscosity decreases with the increase of temperature. The hydration property of OCS is good. The hydration property of OCS is lower than CS. As for OCS, some of–NH2 are occupied by oleoyl groups, which decreases the numbers of–NH2 and also the hydrogen bonds between hydrophilic groups and water.
The self-assembling properties of OCS are analyzed using the fluorescence probe test, the laser light scattering and the transmission electron microscopy. The results show that OCS molecules tend to assemble when the concentration is higher than about 0.1g/l and this trend increases with the rise of concentration. This tend is stronger as the increase of DS and decrease of MW of OCS. The critical aggregation concentration (CAC) of OCS with DS 5, 11, and 27% are 79.43, 31.6, 10 mg/L, respectively, and the CAC of samples with molecular masses of 20, 38, 300, and 1100 kDa are 50.1, 79.43, 125.9, and 630.9 mg/L, respectively. The addition of CH2Cl2 helps to the formation of nanoparticles. Nanoparticles were prepared using O/W emulsification method. Most of the nanoparticles formed are around 200nm and are of a spherical shape, which indicates that the prepared nanoparticles have good structural integrity. The size of self-aggregates decreased as the DS increased, indicating formation of denser hydrophobic cores in high DS sample. Mean diameter of the polymeric amphiphilic nanoparticles of OCS with DS 5% and 11% were around 327.4 nm and 275.3 nm. The increase of DS and decrease of MW might facilitate the formation of nanoparticles but the DS should be not too large to have a compromise between solubility and viscosity.
Rifampicin and doxorubicin, as model drug, are investigated for their release properties in vitro. The FTIR of rifampicin loaded OCS nanoparticles indicate the success of model drug rifampicin to OCS nanoparticles. The loading efficiency increases as the increase of DS and the decrease of MW. The release of rifampicin slower as the DS and MW increased. The release of rifampicin from solution with pH 6.0 and 6.8 was characterized by a faster release than from solution with pH 3.8. The increase of TPP can slow the release of drug. The sample with low concentration of rifampicin release faster and entirely. The FTIR of doxorubicin loaded OCS nanoparticles indicate the success of model drug doxorubicin to OCS nanoparticles. The release speed of doxorubicin of three DS OCS sample is similar. The increase of MW of OCS can slow the release of doxorubicin. The release of doxorubicin is slower in pH 3.8 HAc than in pH 6.8 PBS. The effect of doxorubicin and TPP concentration on release is unconspicuous. The increase of OCS concentration can slow the release of doxorubicin.
Cytotoxicity of OCS is investigated via the red blood cell lysis test and the MTT assay. The red blood cell lysis test shows that each sample can be regarded as non-toxic to red blood cells in the solid state, while the cytotoxicity can not be neglected in the solution state and nanoparticles state. The hemolysis rate of most OCS samples is less than 10% which was regarded as non-toxic effect level. OCS exhibits no cytotoxicity to fetal mouse skin fibroblast with the increase of concentration. All the OCS and OCS nanoparticles have good biocompatibility from the cytotoxicity testing. And the biocompatibility of OCS nanoparticles was better than OCS solution. The toxic effect of nanoparticles in the acidic medium may be due to the fully protonation of the primary amino groups. The biodistribution test of OCS nanoparticles suggests the accumulation in spleen and lung. The mucosa test suggests the OCS can adhere and across the stomach and intestine mucosa. The adherence of OCS nanoparticles onto stomach mucosa is stronger than OCS solution,while that onto intestine mucosa is less than OCS solution.
Oleoyl-carboxymethyl chitosan (OCMCS), Oleoyl-quaternized chitosan (OQCS), oleoyl-chitosan oligosaccharide (OCSO) are synthesized to impvove the solubility of OCS. The results of FTIR confirm the successful modification. The solubility of OCMCS, OQCS, and OCSO are better than OCS. Three kinds of chitosan derivatives have good biocompatibility and hydration property. Nanoparticles of OCMCS, OQCS and OCSO are prepared using an O/W emulsification method. The TEM conformed nanoparticles have good structural integrity.
The PLGA-OCS nanoparticles are prepared using PLGA as hydrophobic core. The effect of PLGA content, OCS concentration, emulsification speed, and H2Cl2 content on the formation of nanoparticles is invisigated. The PLGA content affect the foamation efficiency of slightly. The increase of OCS concentration can decrease the foamation efficiency. The increase of CH2Cl2 concentration can increase the foamation efficiency. The inceease of emulsification speed can increase the foamation efficiency. The increase of emulsification speed can redound to the formation. The incerese of PLGA content, OCS concentration, and CH2Cl2 concentration can redound to the formation of nanoparticles. The Most of the nanoparticles formed are around 200nm and are of a spherical shape.
Oleoylchitosan compound nanoparticles had good biocompability and characteristics which could be the ideal delivery systems of active biomaterials.
引文
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