季铵化两亲性壳聚糖衍生物载药性质研究

合成新型季铵化两亲性壳聚糖衍生物(DEAE-CMC)。用乳化交联固化法制备DEAE-CMC/VB12载药微球。用激光粒径仪、扫描电镜对微球的大小和形态进行表征。载药微球的平均粒径为4.53μm。在pH=7.4磷酸盐缓冲溶液中,DEAE-CMC/VB12载药微球体外药物释放达到平衡时间为60 h,药物包封率为33.70%,载药量为12.47%,平衡时药物累积释放率为56.30%。     

阿司匹林壳聚糖纳米缓释微球的制备及体外释放性能的研究

以自制阿司匹林为药物,壳聚糖为载体,采用乳化-化学交联法制备了阿司匹林-壳聚糖载药微球,确定了阿司匹林-壳聚糖载药微球的制备工艺条件,探讨搅拌速度、阿司匹林/壳聚糖质量比、交联剂戊二醛、乳化剂Span-80用量对微球的药物包封率、载药量和释药性能的影响。研究结果表明,室温条件下,以液体石蜡为介质,选用3%的壳聚糖冰醋酸溶液、按阿司匹林∶壳聚糖=1.5∶1、4%的戊二醛为交联剂、Span-80用量为体积比6%、中等搅拌速度制备出的微球药物包封率可达79%,微球粒径最小可达20 nm,制得的载药微球在16 h内对药物有良好的缓释作用,在25 h之内仍存在缓药效果。     

小檗碱壳聚糖微球制备及其抗真菌活性测定

采用乳化-化学交联法制备了负载小檗碱的壳聚糖微球. 以正交实验对微球形态、粒径、药物包封率和载药率等指标进行了制备工艺条件优化. 显微镜和电镜观察显示微球球形良好,表面光滑,平均粒径约15 mm,包封率为78.98%,载药率为4.78%. 持续30 d的药物释放实验表明,小檗碱可从微球中缓慢释放. 利用生长速率法测定了微球对3种重要植物病原真菌的抑制作用,5 mg/mL微球对番茄早疫病菌(Alternaria solani)的抑菌率达65%.     

壳聚糖聚乙烯醇复合载药微球的制备

以壳聚糖(CS)为基质,通过聚乙烯醇(PVA)的引入制备壳聚糖聚乙烯醇复合载体可以分别采用室温和高温酸催化反应两种方法制备出释药性能和结构形态不同的两种复合载药微球Ⅰ和Ⅱ。其中壳聚糖/聚乙烯醇复合载药微球Ⅰ的制备工艺是调节壳聚糖和聚乙烯醇质量比6/5,复合微球Ⅰ的平均粒径1～20μm,载药量13%,LVFX体外12h累积释放80%。而壳聚糖/聚乙烯醇复合载药微球Ⅱ的平均粒径1.69μm,载药量17.1%,LVFX体外6hr基本完全释放。     

环孢素A海藻酸盐缓释微球的制备及体外释放

针对角膜移植术后免疫排斥治疗研究背景,以多肽类免疫抑制剂环孢素A为药物模型,以海藻酸钠为载体材料,以辛癸酸甘油酯和Tween20为添加剂,采用脉冲电场工艺制备药物控释微球载体,对制备工艺参数进行正交设计优化。载药微球最佳制备处方为海藻酸钠质量分数0.8%、油水体积比1∶1.5、Tween20质量分数6.5%、环孢素A投药量65 mg。载药微球球型度优良,平均粒径(36.344±0.103)μm,粒径分布跨距2.314,药物包封率(86.03±0.65)%。在符合漏槽条件的人工泪液中,7 d累积释放率为56.5%,既能满足手术局部对药物浓度需求,又具有良好缓释性能。     

替米考星交联淀粉载药微球的制备研究

以可溶性淀粉为原料,采用反相悬浮聚合法,合成了替米考星淀粉交联共聚载药微球。探讨了投药量、反应时间、交联剂、乳化剂对替米考星淀粉微球载药量、包封率和微球形貌的影响,运用红外、热重、电镜、粒度分析仪对产物进行了表征。结果表明,最佳制备条件为:替米考星0.02 g,淀粉4 g,乳化剂0.75 g,交联剂0.95 g,反应1.5 h,合成的替米考星淀粉微球载药量2.43%,包封率88.6%。微球粒径分布均匀,外观圆整,表面粗糙,具有较好的热稳定性。     

离子交联法制备负载布洛芬的壳聚糖微球

以壳聚糖为药用载体,焦磷酸钠(TSPP)为离子交联剂,布洛芬为模型药物,采用离子交联法制备壳聚糖微球制剂,考察处方和工艺因素对载药微球的包封率和载药量的影响;采用扫描电子显微镜和红外光谱对微球结构进行表征。实验结果表明:在pH=3.68的壳聚糖溶液中,正负电荷摩尔比20∶1,转速为325r/min,投药量为0.05g是较理想的壳聚糖微球制备条件。而交联剂滴加时间在20～60min之间对微球的载药量和包封率的影响不大。     

壳聚糖-明胶载药微球的制备及释放性能

以壳聚糖（Cs）和明胶（Gel）为原料,采用乳液凝聚法制备了对药物具有缓释作用的微球。以异喹啉为模拟药物,分别通过丙酮浸泡载药／常温干燥法和盐酸浸泡载药／氢氧化钠再生／冷冻干燥法,制得不同载药量的微球,并对其包封率和释放行为进行了研究。结果表明,当戊二醛（GD）与壳聚糖（Cs）的质量比为0．40～0．53,载药量在20％～30％（质量分数）之间时,壳聚糖-明胶载药微球15h后释放75％左右,包封率可以达到40％～50％,为将壳聚糖。明胶共混微球应用于生物医学领域提供了试验基础。     

pH响应性的虾青素壳聚糖微球制备及应用

以氯乙酸和壳聚糖为原料，通过N,O-羧甲基化化学改性方法制备了水溶性羧甲基壳聚糖，并以此为原料通过乳液法制备羧甲基壳聚糖微球和羧甲基壳聚糖负载虾青素微球。考察了羧甲基壳聚糖微球的形态、分散性和粒径。结果表明，微球最佳制备条件为：羧甲基壳聚糖含量（以水相即去离子水质量为基准，下同）1.0%，油水体积比1∶1，表面活性剂Span 80含量（以油相即液体石蜡体积为基准，下同）4.0%，交联剂戊二醛含量（以油相即液体石蜡体积为基准，下同）7.5%，剪切速率4000 r/min。红外测试表明，微球成功负载虾青素，在虾青素初始添加量为20mg的载药率和包封率分别为10.74%和67.24%。在模拟胃液和模拟肠液中，负载虾青素微球的释放率分别为10%和85%。羧甲基壳聚糖可以用作药物载体。     

大蒜素/海藻酸钠/明胶/壳聚糖复合微球的制备及性能

以大蒜素为模型药物,采用复凝聚法制备了海藻酸钠/明胶/壳聚糖复合微球,考察了不同条件对微球溶胀性、载药性能和缓释性能等指标的影响。结果表明,明胶和海藻酸钠(质量比为1∶3)为2%,大蒜素投入量与混合胶比为1∶2时,制备的载药微球(DSGCM)外形规则,粒径分布在0.8~0.9mm之间,载药量为24.3%,包封率为69.4%,复合微球具有p H敏感性,在p H=7.4介质中微球溶胀率达到450%,药物释放过程符合Higuchi方程,明胶的加入可以延缓DSGCM复合微球的药物释放性能。     

载5-氟尿嘧啶壳聚糖/明胶微粒的制备及药物释放性能

壳聚糖及明胶是生物相容性良好的高分子药物载体,制备载5-氟尿嘧啶壳聚糖/明胶微粒,并进行体外释药研究。以石蜡油为外相,壳聚糖/明胶为内相,用乳化交联法制备微粒,以吸附药量为指标,采用正交设计实验优化获得最佳制备条件,用红外光谱、SEM对最佳条件下制备的微粒进行表征。结果表明壳聚糖/明胶微粒的最佳制备条件如下:水油比1:7,壳聚糖/明胶浓度比1:3,乳化剂100.7mmol/L,乳化5min,乳化温度60℃,交联剂戊二醛用量5.5mmol/L,交联时间1h。在此条件下,载药微粒的载药量为34.93%,包封率为38.36%。红外光谱图表明壳聚糖/明胶微粒已负载5-氟尿嘧啶,SEM表明微粒成球状,表面较光滑。模拟胃肠释放表明,微粒具有一定的缓释性能。采用乳化交联法制备载5-氟尿嘧啶壳聚糖/明胶微粒方法简单,重现性好,且其体外释放实验显示出明显的缓释作用。     

阿司匹林壳聚糖-明胶载药微胶囊的制备及性能研究

以阿司匹林为囊芯,壳聚糖和明胶为壁材,采用乳化交联法制备了明胶-壳聚糖微胶囊,考察了芯壁比、水油体积比、乳化剂用量、交联时间等因素对微胶囊性能的影响.采用高效液相色谱法来测定微胶囊的载药量、包封率和释放性能.研究发现,当芯壁比为1∶1,水油体积比为1∶3,乳化剂Span-80用量为5％,交联时间为2h的条件下制备的微胶囊形状规整,载药量为47.99％,包封率为83.18％,且在人工肠液中具有明显的缓释效果.     

5-FU-PLGA复乳微球的制备及体外释放

采用乳化溶剂挥发法制备W/O/W型5-FU-PLGA复乳微球,采用单因素设计考察了第一相体积比(内水相与油相)、第二相体积比(初乳与外水相)对复乳稳定性的影响,采用正交设计考察了搅拌温度、搅拌时间、辅料浓度和有机相中载体材料浓度对微球质量的影响,并对制备条件进行优化。最适宜制备条件为:第一相体积比为1:2,第二相体积比为1:1,搅拌温度为10 ℃、搅拌时间为6 h、辅料浓度为0.5%、有机相中载体材料浓度为15%。依据最适宜条件制备的微球圆整度良好、粒径范围窄,平均粒径5.20 μm,载药量为5.34%,包封率为77.22%。体外释放试验表明微球具有明显的缓释效果,释放行为符合Higuchi模型。     

Encapsulation and release of cladribine from chitosan nanoparticles

This study shows the potential of chitosan (CH) nanoparticles as both an oral and IV drug delivery system using the anticancer drug cladribine as a model drug. Smooth, spherical nanoparticles were prepared by the ionotropic gelation of CH with sodium tripolyphosphate. Nanoparticle size depended on degree of hydration, drug loading, and crosslinking conditions, with the smallest nanoparticles in the size range of 212 ± 51 nm. Cladribine was entrapped in the CH matrix with an entrapment efficiency of up to 62%, depending on the initial loading. The release of cladribine followed a near‐Fickian diffusion rate over the first several hours and then reached a plateau. A second release phase began after 30–40 h of incubation in the release medium, and proceeded until ～100 h. Loaded CH nanoparticles that were crosslinked with genipin showed a delayed release profile, with only 40% of loaded drug being released after 100 h. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013     

PVA-SA复合微球的制备及性能研究

用溶液共混法制备聚乙烯醇-海藻酸钠(PVA-SA)复合微球,考察了SA质量分数、PVA质量分数、CaCl2质量分数、m(PVA)/m(SA)和干燥方式对PVA-SA复合微球制备的影响,并测定了微球的含水率、溶胀率、载药量和包封率,通过红外光谱(FTIR)对微球进行了表征,研究了不同m(PVA)/m(SA)的PVA-SA复合微球对药物的缓释作用。结果表明,SA质量分数为6%,PVA质量分数为10%,CaCl2质量分数为5%,m(PVA)/m(SA)为1∶3时,可以制备出各项性能较好的微球,其载药率30.24%,包封率90.11%,并且有良好的缓释效果。     

Synthesis and characterization of polyacrylamide‐grafted chitosan hydrogel microspheres for the controlled release of indomethacin

Microspheres of polyacrylamide‐grafted‐chitosan crosslinked with glutaraldehyde were prepared and used to encapsulate indomethacin, a nonsteroidal anti‐inflammatory drug. The microspheres were produced by the water/oil emulsion technique and encapsulation of indomethacin was carried out before crosslinking of the matrix. The extent of crosslinking was analyzed by Fourier transform infrared spectroscopy and differential scanning calorimetry. Microspheres were characterized for drug‐entrapment efficiency, particle size, and water transport into the polymeric matrix as well as for drug‐release kinetics. Scanning electron microscopy confirmed the spherical nature and surface morphology of the particles with a mean particle size of 525 μm. Dynamic swelling experiments suggested that, with an increase in crosslinking, the transport mechanism changed from Fickian to non‐Fickian. The release of indomethacin depends upon the crosslinking of the network and also on the amount of drug loading. This was further supported by the calculation of drug‐diffusion coefficients using the initial time approximation. The drug release in all the formulations followed a non‐Fickian trend and the diffusion was relaxation‐controlled. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 87: 1525–1536, 2003     

Preparation,characterization, and salicylic acid release behavior of chitosan/poly(vinyl alcohol) blend microspheres

Blend microspheres of chitosan (CS) with poly(vinyl alcohol) (PVA) were prepared as candidates for oral delivery system. CS/PVA microspheres containing salicylic acid (SA), as a model drug, were obtained using the coacervation‐phase separation method, induced by addition of a nonsolvent (sodium hydroxide solution) and then crosslinked with glutaraldehyde (GA) as a crosslinking agent. The microspheres were characterized by Fourier transform infrared spectroscopy, differential scanning calorimetry (DSC), and scanning electron microscopy. Percentage entrapment efficiency, particle size, and equilibrium swelling degree of the microsphere formulations were determined. The results indicated that these parameters were changed by preparation conditions of the microspheres. Effects of variables such as CS/PVA ratio, pH, crosslinker concentration, and drug/polymer (d/p) ratio on the release of SA were studied at three different pH values (1.2, 6.8, and 7.4) at 37°C. It was observed that SA release from the microspheres increased with decreasing CS/PVA ratio and d/p ratio whereas it decreased with the increase in the extent of crosslinking. It may also be noted that drug release was much higher at pH 1.2 than that of at pH 6.8 and 7.4. The highest SA release percentage was obtained as 100% for the microspheres prepared with PVA/CS ratio of 1/2, d/p ratio of 1/2, exposure time to GA of 5 min, and concentration of GA 1.5% at the end of 6 h. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2009     

静电喷射技术制备可酸致突释给药的壳聚糖微颗粒

利用静电喷射技术,以西咪替丁作为模型药物,混有药物的壳聚糖水溶液作为喷射液,甲苯/正己醇的混合溶液作为接收液,成功制备得到可在酸性条件下溶解并突释给药的壳聚糖载药微颗粒。系统考察了交联剂含量对壳聚糖微颗粒的药物包封率以及载药量的影响,并研究了壳聚糖微颗粒在酸性条件下的溶解特性以及在体外的突释给药效果。结果表明,当交联剂质量分数为2%时,壳聚糖微颗粒的包封率及载药量最大,分别为80%和3.8%。由于对苯二甲醛与壳聚糖交联形成的Schiff-base结构,使得壳聚糖微颗粒能够在中性条件下保持结构完整,而在酸性条件下由于Schiff-base结构的不稳定性致使微颗粒迅速溶解。因此,体外释药实验结果显示,在pH = 2、37℃的模拟胃酸溶液中,1min内壳聚糖微颗粒即可达到最大释药效果,而在pH = 6.4、37℃的水溶液中,壳聚糖微颗粒可以较长时间保持稳定,药物释放缓慢。这种具有酸致突释释药性能的壳聚糖微粒载体在胃部给药系统方面有良好的应用前景。     

水杨酸壳聚糖/卵磷脂纳米粒的制备

采用溶剂注入法制备水杨酸壳聚糖/卵磷脂纳米粒。考察了粒子结构、形貌特征及表面电位等性能,并探讨了制备工艺对药物包封率的影响。确定最佳制备工艺为:卵磷脂质量浓度20 g/L、卵磷脂与壳聚糖及水杨酸与载体的质量比分别为3∶1和1∶6、水相pH=4。所制备的水杨酸壳聚糖/卵磷脂固体纳米粒子为球形粒子、表面电位+18.7 mV、包封率及载药量可分别达到55%和8.07%。