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%。     

快速膜乳化法制备载生长激素释放肽-6的PLGA微球

采用快速膜乳化法制备了聚(乳酸-羟基乙酸)(PLGA)微球,得到制备PLGA微球的优化条件为：过膜压力5 kPa,水相中PVA浓度19 g/L,油/水相体积比1:10,该条件下所制空白微球的平均粒径约为24 mm,粒径分布系数Span<0.7. 在此基础上制备载生长激素释放肽-6(GHRP-6)微球,油相乳化剂浓度2.5 g/L、外水相中NaCl浓度10 g/L条件下所制载GHRP-6微球包埋率最高可达85%,初乳制备方式对药物包埋率及体外释放行为均有较大影响,超声法制备的初乳所得微球内部结构紧密,药物包埋率较高(85%),但释药缓慢;而均质法制备的初乳所得微球内部结构疏松,药物包埋率较低(76.8%),但在体外释放更完全.     

快速膜乳化法制备胸腺法新长效缓释微球

采用快速膜乳化技术结合溶剂蒸发法制备以生物可降解聚乳酸-羟基乙酸(PLGA)为载体的胸腺法新载药微球,考察了PLGA分子量、油相中PLGA和乳化剂浓度、外水相pH值和内水相体积等对微球包埋率和粒径的影响. 结果表明,制备粒径均一的PLGA载药微球的优化条件为：PLGA分子量51 kDa,油相中PLGA和乳化剂浓度为100和10 g/L,内水相体积0.5 mL,外水相pH值为3.5. 该条件下所制载药微球粒径均一性好(Span<0.7),药物包埋率高达80%以上,突释率24 h内低于20%,线性持续稳定释药时间长达30 d.     

壳聚糖微球及其与白油混合乳液对禽用新流二联疫苗佐剂的免疫效果

用不同粒径的壳聚糖季铵盐凝胶微球及其与白油的混合乳液吸附新城疫及禽流感灭活抗原,评价其对新流二联灭活疫苗的免疫增强效果.结果表明,吸附时间2 h、微球浓度2 mg/m L、微球粒径1μm为吸附新流二联灭活抗原的最佳条件,抗原吸附率达90%.免疫SPF鸡后,壳聚糖季铵盐微球及混合乳液均能显著提高新城疫及禽流感病毒特异性抗体效价,且混合乳液组显著优于微球组.与白油佐剂相比,壳聚糖季铵盐微球及混合乳液均能显著增强细胞免疫,淋巴细胞增殖水平为纯抗原组的1.5倍,具有用作禽类疫苗佐剂的巨大潜力.     

丝素-羟丙基壳聚糖微球的结构和释药性能

以胰岛素为目标药物,以丝素(SF)和羟丙基壳聚糖(HPCS)为包药材料,复凝聚法制备SF-HPCS载药微球。采用红外光谱(FTIR)、扫描电镜(SEM)、X射线衍射(XRD)、热重分析(TGA)等对载药微球的结构、外部形貌及热性能等进行了表征。结果表明,所制备的载药微球表面密实,平均粒径22.4μm,呈正态分布;载药微球对胰岛素的包埋率达73.6%,大于HPCS载药微球(64.3%)及壳聚糖(CS)载药微球(57.1%);SF-HPCS载药微球在人工胃液中4h内累计释药率为21.3%,在人工肠液中24h内累计释药率达81.2%,48h累计释药率为92.2%,释放过程平稳、缓慢。     

膜乳化法与复乳法结合制备粒径均一的PELA载溶菌酶微球

采用快速膜乳化技术与复乳-溶剂去除法制备了尺寸均一的单甲氧基聚乙二醇-聚-DL-乳酸(PELA)载溶菌酶微球,比较了膜材种类和有机溶剂类型对微球中药物包埋率和活性保持的影响. 研究结果表明,该方法能快速制备粒径均一的载药微球,在油相与外水相体积比为1:6的条件下,微球粒径分布系数小于20%,而且该方法对膜材和有机溶剂有很好的普适性. 以PELA为膜材、乙酸乙酯为有机溶剂,采用溶剂扩散法制备的载药微球包埋率高达95.7%,并且能保持高的活性.     

快速膜乳化法制备载醋酸曲普瑞林PLGA微球

以生物可降解聚合物聚(乳酸?羟基乙酸)(PLGA)为载体,以160 g/L明胶水溶液为内水相、含500 g/L PLGA的二氯甲烷为油相,采用快速膜乳化和溶剂蒸发法制备了粒径均一的载醋酸曲普瑞林PLGA微球,微球粒径约30 mm,粒径分布系数Span<0.8,醋酸曲普瑞林包埋率达80.12%,药物在磷酸盐缓冲液中释放36 d的释放率为72.60%,体外释放行为良好.     

壳聚糖/聚丙烯酸共聚物微球的制备及性能

以环己烷为油相,壳聚糖溶液为水相,运用反相乳液聚合法制得了具有pH敏感性的壳聚糖/聚丙烯酸共聚物微球。讨论了微球在pH=1～10缓冲溶液中的溶胀率变化,研究表明,微球在强酸性(pH≈1)和碱性(pH>7)条件下,溶胀率均在10倍以上;而在pH=2～6时溶胀较差,当pH=4时出现最低值,溶胀率低于1倍。光学显微镜所观察到的微球粒径均在40μm以内,且大小均匀。采用傅里叶红外光谱仪分析了不同配比样品特征峰的峰值和峰面积的变化。用722光栅分光光度计研究了共聚物微球包埋考马斯亮蓝的溶胀释放过程。     

壳聚糖季铵盐表面修饰对载紫杉醇PLGA微球体外药效学的影响

采用聚(乳酸-羟基乙酸)共聚物(PLGA)纳微球装载紫杉醇,并用壳聚糖季铵盐(HTCC)对PLGA微球表面进行镀层修饰,比较了修饰前后载药微球的形貌、粒径、电位、载药率、释药行为和细胞杀伤效果. 结果表明,修饰后微球表面圆整光滑,平均粒径为882 nm,载药率可达5.15%,包埋率达70.46%,体外释药22 d累积释药率为70.17%,与修饰前没有显著性差异;但修饰后微球表面电荷由修饰前的-14.8 mV翻转为+36.7 mV,肿瘤细胞对PLGA和HTCC-PLGA载药微球的内吞量分别是Taxol?的5.6和9.7倍,且HTCC-PLGA载药微球对细胞杀伤效果显著,是一种有潜力的难溶性药物递送系统.     

季铵盐改性壳聚糖微球对含铬废水的吸附性能

用2,3-环氧丙基三甲基氯化铵对壳聚糖进行改性得到壳聚糖季铵盐,进一步通过乳化交联法合成壳聚糖季铵盐微球,采用傅里叶变换红外光谱（FT-IR）、差热热重分析（TG-DTG）、X-衍射衍射（XRD）和扫描电镜（SEM）对其进行表征分析。此外,研究了壳聚糖季铵盐的浓度、油水比、交联剂用量对合成的壳聚糖季铵盐微球吸附Cr(Ⅵ)性能的影响,并考察了重铬酸钾初始浓度、pH值、壳聚糖季铵盐微球添加量对Cr(Ⅵ)吸附效果的影响。结果表明：HACC浓度为0.8%(w/V)、油水比为8∶1、壳聚糖季铵盐与交联剂质量比为1.64的条件下,可以制备出球型圆整、分散性好的壳聚糖季铵盐微球。在酸性条件和较低浓度的重铬酸钾均有利于壳聚糖季铵盐微球对Cr(Ⅵ)的吸附。     

Controlled release of berberine hydrochloride from alginate microspheres embedded within carboxymethyl chitosan hydrogels

Berberine hydrochloride is a natural medicine with wide clinical application. In this article, berberine hydrochloride was entrapped into alginate microspheres via an emulsification/gelation method. The size distribution of the microspheres was determined by a laser particle sizer. Drug distribution within the microspheres was determined by confocal laser scanning microscopy. Those drug‐loaded microspheres were further entrapped into carboxymethyl chitosan (CMC) hydrogel to form a new drug‐delivery system (DDS). The surface morphology of the DDS was observed using metallographic microscopy and scanning electron microscopy (SEM). The compression strength of the DDSs with alginate microspheres was found significantly higher than that of the pure hydrogel. The drug‐release performances of the DDS in phosphate buffer solution (PBS, pH 7.4), saline solution (pH 6.3), and hydrochloric acid solution (HAS, pH 1.2) were also studied. Decay of the DDS in PBS within 72–80 h results in a faster release; however, the steady release in saline solution could last for all the testing period without cleavage of the DDS. In HAS, because of the shrinkage of the DDS, release is fast in the first period and remains steady later. The DDS exhibits prospective in controlled steady release of drugs. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2011     

Preparation,Characterization, and Drug-Release Behaviors of a pH-Sensitive Composite Hydrogel Bead Based on Guar Gum,Attapulgite, and Sodium Alginate

A novel guar gum-g-poly (acrylic acid)/attapulgite/sodium alginate (GG-g-PAA/APT/SA) composite hydrogel bead with excellent pH sensitivity was prepared via a facile ionic gelation approach and characterized by FTIR and SEM techniques. The effect of APT content on the encapsulation efficiency (EE), swelling ratio, and drug release behaviors of the beads was investigated and the in-vitro release kinetics were also evaluated using diclofenac sodium (DS) as the model drug. The results indicate that the burst release effect of DS drug was eliminated due to the incorporation of APT, and the DS cumulative release was clearly decreased with increasing the APT content.     

Enhanced gastric retention and drug release via development of novel floating microspheres based on Eudragit E100 and polycaprolactone: synthesis and in vitro evaluation

Eudragit E 100 and polycaprolactone (PCL) floating microspheres for enhanced gastric retention and drug release were successfully prepared by oil in water solvent evaporation method. Metronidazole benzoate, an anti-protozoal drug, was used as a model drug. Polyvinyl alcohol was used as an emulsifier. The prepared microspheres were observed for % recovery, % degree of hydration, % water uptake, % drug loading, % buoyancy and % drug release. The physico-chemical properties of the microspheres were studied by calculating encapsulation efficiency of microspheres and drug release kinetics. Drug release characteristics of microspheres were studied in simulated gastric fluid and simulated intestinal fluid i.e., at pH 1.2 and 7.4 respectively. Fourier transform infrared spectroscopy was used to reveal the chemical interaction between drug and polymers. Scanning electron microscopy was conducted to study the morphology of the synthesized microspheres.     

Preparation and evaluation of poly(3‐hydroxybutyrate) microspheres containing bovine serum albumin for controlled release

The utility of the Poly(3‐hydroxybutyrate) (PHB) to encapsulate and control the release of bovine serum albumin (BSA), via microspheres, was investigated. Various preparing parameters, including polymer concentration in oil phase, emulsification concentration in external water phase, volume ratio of inner water phase to oil phase, and volume ratio of primary emulsion to external water phase were altered during the microspheres production. The effects of these changes on the morphological characteristics of the microspheres, size of the microspheres, drug loading, encapsulation efficiency, and drug release rates were examined. The diameter of the microspheres ranged from 6.9 to 20.3 μm and showed different degrees of porous structure depending on the different preparation parameters. The maximum and minimum BSA encapsulation efficiency within the polymeric microspheres were 69.8 and 7.5%, respectively, varying with preparation conditions. The controlled release characteristics of the microspheres for BSA were investigated in pH 7.4 media. The initial BSA burst release from 8.9 to 63.1% followed by constant slow release for 28 days was observed for BSA from BSA‐loaded microspheres and followed the Higuchi matrix model. So, the release behavior of microspheres showed the feasibility of BSA‐loaded microspheres as controlled release devices. Pristine BSA, pristine PHB microspheres, and BSA‐loaded microspheres were analyzed by Fourier transform infrared spectrophotometer, which indicated no interaction between BSA and PHB. Differential scanning calorimetry on BSA‐loaded microspheres indicated a molecular level dispersion of BSA in the microspheres. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2008     

海藻酸钙/埃洛石载药微球的制备与缓释盐酸二甲双胍性能

缓释可提高药物利用率,降低其毒副作用。采用交联法制备了海藻酸钙/埃洛石载药微球,以载药微球对盐酸二甲双胍（MH）药物的包封率和缓释效果为考察对象,研究了载药微球的制备工艺和缓释性能,并通过SEM、FTIR和TGA对其结构进行了表征。结果表明：在交联温度为0℃、海藻酸钠用量为1g、埃洛石添加量为2g时,能得到较优的载药微球包封率（79.23%）。上述条件下制得的复合载药微球在pH=6.8的磷酸盐缓冲液中能有效缓释,且720min后缓释度可达85.83%,说明其具有较好的pH敏感性和缓释效果。SEM表明海藻酸钙颗粒与埃洛石在载药微球内部形成复合结构,FTIR表明MH主要以物理包埋的形式于载药微球中,TGA表明添加埃洛石可以提高复合材料在200℃以上的热稳定性。     

Preparation of bioactive glycosylated glial cell‐line derived neurotrophic factor‐loaded microspheres for medical applications

Poly (lactic‐co‐glycolic acid) (PLGA)‐coated gelatin microspheres containing glial cell‐line derived neurotrophic factor (GDNF) were developed by thermal gelation through a water‐in‐oil emulsion technique. Gelatin types (A and B) at four different pH levels were investigated for their influences on the morphology, the microsphere size, the zeta potential, and the swelling ability. The encapsulation of GDNF and the release characteristics of GDNF were also determined using enzyme‐linked immunosorbent assay (ELISA). The maximum cumulative released amounts of GDNF from the microspheres were increased from 50 to 90% after 4 d (based on the actual amount of the GDNF). Thus, the release of the GDNF contents in the microspheres depends on the amount of GDNF. Trigeminal ganglion cells (TGCs) were used to study the bioactivity of GDNF released from the microspheres, which was proven to retain its bioactivity in promoting the TGCs' neurite outgrowth. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 40167.