Preparation of amifostine polylactide-co-glycolide microspheres and its irradiation protective to mouse through oral administration

The objectives of this study were to prepare the amifostine polylactide-co-glycolide (PLGA) microsphere and investigate its irradiation protective to mouse through oral administration. Amifostine-loaded PLGA microsphere was formulated using a modified double emulsion-solvent evaporation technique. The microsphere particle was spherical with a mean diameter of 2.8 ± 0.1 μm. Release data of amifostine PLGA microsphere was tested in phosphate-buffered saline at 37°C using a dialysis method and its release profiles was biphasic, showing a relatively large burst effect (50%) over the first 6 h, followed by a slower release phase, which sustained with 80% amifostine released in 48 h and almost 100% release till 6 days (144 h). A diffusion-controlled release model (Higuchi equation, R2 = 0.9725) was obtained for amifostine releasing from PLGA microsphere. The radiation experiment was performed by applied cobalt-60 γ-radiation source. One hour before γ-radiation exposure, the mouse was orally given free amifostine and PLGA microsphere, respectively. The irradiation effects, such as blood cell concentration, superoxidase dismutase (SOD) activity and malondialdehyde (MDA) level were monitored. The results indicated that amifostine PLGA microsphere was more irradiation protective to mouse than that of free amifostine under the same oral administration route.     

微波辐射下交联壳聚糖微球的制备及吸附性能研究

微波辐射下,以壳聚糖为原料,甲醛为预交联剂,环氧氯丙烷为交联剂,制得甲醛环氧氯丙烷交联壳聚糖微球树脂,研究了合成条件对微球吸附性能的影响,并采用傅里叶红外光谱仪和电子扫描电镜对树脂的微观结构和形貌进行表征。结果表明,树脂具有很好的球形;Shiff碱反应能够很好地保护壳聚糖上的氨基;交联剂用量、搅拌速率和酸处理条件对树脂的吸附性能的影响较大。当合成条件为搅拌速率600r/min、甲醛1.5mL、环氧氯丙烷3mL、酸化时间8min、盐酸用量30mL,所得交联壳聚糖微球对Cu(Ⅱ)的吸附容量可达到269.83mg/g。     

TiO2膜/硅胶复合微球的制备及光催化性能

采用硅胶微球为载体,以TiO2溶胶为涂膜液,制备TiO2膜/硅胶复合微球,用XRD,FT-IR和显微镜等对催化剂的物相、形貌行了表征,并考察其对甲基橙溶液的光催化降解性能.结果表明:TiO2膜和硅胶微球之间存在化学键合作用,涂膜5层微球粒径为0.5～3mm,呈白色,水溶液中透明,是理想的光催化材料.其光催化性能随涂膜层数和催化剂用量的增加而增大,涂膜的5层微球甲基橙降解率可达85%.     

单分散聚苯乙烯微球的制备及其模板表面形貌分析

以丙烯酸为分散剂、过硫酸铵为引发剂、水为分散介质进行了聚苯乙烯微球的制备,讨论了丙烯酸浓度、引发剂浓度、pH值、反应时间与温度等因素对微球制备的影响规律并确定了最佳的制备工艺参数。采用旋涂法制备聚苯乙烯微球模板,并发现其表面排布存在两种排列方式:(1)呈现面心立方〈100〉面的排列方式;(2)呈现面心立方〈111〉面的排列方式。     

壳聚糖-固态分散体载药微球的制备及性能研究

首先采用不同分子量的壳聚糖通过乳化-化学交联法制备了4种不同的壳聚糖载药微球。通过对微球的粒径、溶胀率、载药率、包封率等指标检测以及缓释性能的研究,发现分子量为240kDa的壳聚糖制备的载药微球缓释效果明显,载药率、包封率均较高,综合性能优于其它分子量壳聚糖制备的微球。利用该分子量壳聚糖包埋固态分散体制备了壳聚糖-固态分散体载药微球,改善了药物的溶解性并具有药物缓释作用。因此,壳聚糖-固态分散体载药微球是一种理想的药物缓释体系,可以用于包埋溶解性差,生物半衰期短,对胃肠刺激性强的药物。     

Pharmacokinetics and tissue distribution of amphotericin B following oral administration of three lipid-based formulations to rats

The objective of this study was to assess the pharmacokinetics and tissue distribution of amphotericin B (AmB) in rats following oral administration of three lipid-based formulations (iCo-009, iCo-010 and iCo-011). The lipid-based formulations were administered to rats at a dose of 10?mg/kg and blood samples were withdrawn at predose, 1, 2, 4, 6, 8, 10, 12, 24, 48 and 72?h, after which the animals were sacrificed and the body organs were collected for AmB quantification using a validated HPLC method. Plasma pharmacokinetics parameters were determined using non-compartmental analysis. The disappearance of AmB from plasma was the slowest following the administration of iCo-010 with MRT of 63?h followed by iCo-009 then iCo-011 (36 and 27?h). The AUC_0-24h of iCo-009 and iCo-010 was 1.5–2-fold higher than that of iCo-011. The kidney exposure was comparable between iCo-009 and iCo-010 and was higher than that of iCo-011. The lung exposure was the highest following iCo-010 administration as compared to that of iCo-009. The distribution of AmB from plasma to tissues resulted in a high accumulation of AmB overtime with slow back-distribution to plasma. The pharmacokinetics profiles varied among the three formulations, despite the similarity in lipid composition between iCo-010 and iCo-011 and the presence of Peceol® as a common component in the formulations. The administration of oral iCo-010 could lead to higher steady state concentrations in the tissues after multiple dosing, which could lead to enhanced eradication of tissue borne fungal and parasitic infections.     

聚氨酯/有机刚性微球复合材料的制备和表征

采用乳液聚合的方法合成了表面富含羧基的核壳结构有机刚性微球,并以有机刚性微球、聚已二酸乙二醇酯二醇(PEA,M=1510)、甲苯二异氰酸酯(TDI)、扩链剂(MOCA)为原料,采用预聚法制备出新型聚氨酯/有机刚性微球复合材料并对其性能进行了表征.结果表明:有机刚性微球的添加量为1%～3%时,复合材料的力学性能最佳,耐溶剂性有所下降.     

氮掺杂TiO_2中空复合微球的制备及可见光光催化性能

为了提高TiO2的可见光光催化性能,以微米级聚苯乙烯微球为模板,钛酸四丁酯为前驱体,三乙胺为氮源,采用静电吸附自组装法制备了粒径为1.20μm、壳层的厚度约为30nm且球形形貌良好的氮掺杂TiO2中空复合微球,采用SEM、XPS、XRD和紫外-可见分光光度计研究了其结构及光催化性能。结果表明:氮进入TiO2晶格内取代了部分O并改变了晶格中Ti和O的化学状态,但对TiO2晶型结构没有明显影响;氮掺杂后的TiO2中空复合微球禁带宽度变窄,氮掺杂TiO2中空复合微球不仅在紫外区有较强的光吸收能力,在可见光区也表现出较强的光响应性,对甲基橙的光催化降解率较Degussa P25型纳米TiO2的明显增强。研究结果对TiO2在光催化领域的应用具有理论指导意义。     

双氯灭痛壳聚糖水凝胶微球的制备及其性能研究

在Span80与植物油形成的反相胶束体系中,通过戊二醛交联制备出壳聚糖水凝胶微球(CHM)。采用红外光谱和透射电镜等方法对CHM结构及粒子形态进行了研究。同时对CHM的溶胀度及其对模型药物双氯灭痛的体外释放行为进行了考察。结果表明,CHM具有较好的控制药物释放的作用。交联程度对微球粒径、溶胀度及药物释放性能影响较大。     

可生物降解聚合物微球的制备及载药应用

综述了近年来合成生物降解聚合物微球的种类、制备方法及作为药物载体的应用.结果表明,这类聚合物微球具有良好的安全性、生物相容性和生物降解性,在药物缓释、控释和疾病的治疗中具有非常重要的作用和应用前景.     

聚乳酸头孢唑啉钠微球的制备及其性能表征

采用复乳法制备聚乳酸．头孢唑啉钠（PLA-CEZ）微球．扫描电子显微镜（SEM）和差热分析（DTA）结果表明，PLA-CEZ呈现完整的球形且聚乳酸和模型药物能够有机地结合为一体．同时，探讨了聚乳酸分子量大小及释药介质对载药微球释放速度的影响；释药曲线显示，PLA-CEZ微球具有很好的缓释效果．     

卵磷脂/果胶锌复合凝胶球的制备及性能

采用滴制法,以吲哚美辛(IDM)为模型药物,皂化高甲氧化苹果果胶为骨架材料,氯化锌为交联剂,并复合卵磷脂(PC)制成吲哚美辛卵磷脂/果胶锌复合凝胶球.针对工艺参数对复合凝胶球粒径、粒重、载药量与包封率以及体外释药性能的影响进行了讨论.凝胶球均成均匀球形,粒径1.13～1.42 mm,粒重1.13～2.32 mg,包封率范围70.72％～94.76％,载药量范围5.84％～13.54％.同时实验结果表明,卵磷脂的加入比例、药胶比(吲哚美辛与果胶的质量比)和皂化用NaOH浓度对复合凝胶球的形态、载药及释药性能均有明显影响.其中,卵磷脂的加入使复合凝胶球载药性能和在模拟肠液中的缓释性能明显提高,当卵磷脂与果胶的质量比为5∶4,皂化用NaOH浓度为30 g/L,药胶质量比1∶4时,复合凝胶球在肠模拟液中8h累计释药率为8.93％.稳定性实验结果表明,在高温和光照的条件下放置,卵磷脂/果胶锌复合凝胶球比原药及果胶锌凝胶球具有更好的稳定性,显示出卵磷脂对果胶锌复合凝胶球在结肠定位给药系统的明显改善作用.     

Preparation and in vitro evaluation of chitosan microspheres containing prednisolone: comparison of simple and conjugate microspheres

The purpose of the present study was to obtain a novel microparticulate formulation of prednisolone, which was adequate for the treatment of inflammatory bowel disease (IBD). The formulations prepared were evaluated in vitro. Two types of chitosan microspheres containing prednisolone, named Ch-Pred and Ch-SP-MS, were prepared by an emulsification-solvent evaporation method using a chitosan-prednisolone mixture and a chitosan-succinyl-prednisolone conjugate (Ch-SP), respectively. Ch-Pred and Ch-SP-MS were obtained in almost spherical shape. Ch-Pred showed a relatively high drug content of 13.2% (w/w), but the particle size was distributed from 10 to 45 µm, and a large initial burst release of approximately 60% was observed. On the other hand, although Ch-SP-MS exhibited a fairly low drug content of 3.5% (w/w), their particle size ranged from several hundred nanometers to 20 µm, with the mean diameter of 5 µm, and a gradual drug release profile was achieved. These characteristics on particle size and in vitro release suggested that Ch-SP-MS should have good potential as a microparticulate system for the treatment of IBD.     

卵磷脂/果胶锌复合凝胶球的制备及性能

采用滴制法, 以吲哚美辛(IDM)为模型药物, 皂化高甲氧化苹果果胶为骨架材料, 氯化锌为交联剂, 并复合卵磷脂(PC)制成吲哚美辛卵磷脂/果胶锌复合凝胶球。针对工艺参数对复合凝胶球粒径、粒重、载药量与包封率以及体外释药性能的影响进行了讨论。凝胶球均成均匀球形, 粒径1.13~1.42 mm, 粒重1.13~2.32 mg, 包封率范围70.72%~94.76%, 载药量范围5.84%~13.54%。同时实验结果表明, 卵磷脂的加入比例、药胶比(吲哚美辛与果胶的质量比)和皂化用NaOH浓度对复合凝胶球的形态、载药及释药性能均有明显影响。其中, 卵磷脂的加入使复合凝胶球载药性能和在模拟肠液中的缓释性能明显提高, 当卵磷脂与果胶的质量比为5:4, 皂化用NaOH浓度为30 g/L, 药胶质量比1:4时, 复合凝胶球在肠模拟液中8 h累计释药率为8.93%。稳定性实验结果表明, 在高温和光照的条件下放置, 卵磷脂/果胶锌复合凝胶球比原药及果胶锌凝胶球具有更好的稳定性, 显示出卵磷脂对果胶锌复合凝胶球在结肠定位给药系统的明显改善作用。     

Preparation and characterization of chitosan microspheres containing doxifluridine

Chitosan microspheres containing 5-fluorouracil (5-FU), tegafur (FT), and doxifluridine (DFUR) were prepared by the dry-in-oil method using silicone oil with no surfactant as a dispersion medium. For DFUR-containing chitosan microspheres (DFUR-M), reacetylation with acetic anhydride or coating using chitosan and glutaraldehyde was performed. DFUR-M, reacetylated DFUR-M, and chitosan-coated DFUR-M were investigated on in vitro drug release, and the former two microspheres were examined for in vivo degradation after subcutaneous (s.c.) implantation in mice, and in vivo plasma concentration-time profiles after s.c. implantation in rats. The present method gave fairly large microspheres purely composed of chitosan and drug because of no use of surfactant, which showed the mean particle diameters of 300-900 µm and the drug contents of 4-22% (w/w). Encapsulation efficiency of DFUR was higher than that of 5-FU and FT. DFUR-M and reacetylated DFUR-M exhibited spherical shape except chitosan-coated DFUR-M. DFUR-M showed high initial rapid release, which was suppressed to some extent by reacetylation or chitosan coating. DFUR-M and reacetylated DFUR-M subcutaneously implanted were gradually degraded, and approximately half or a little more of the microspheres disappeared from the implanted site at 3 weeks postimplantation. DFUR-M and reacetylated DFUR-M implanted subcutaneously gave similar plasma concentration-time profiles of DFUR, which did not indicate prolonged release in vivo. DFUR-containing chitosan microspheres with fairly large size and good drug content could be obtained by the present preparation but remained to be improved for drug release properties.     

Ondansetron-loaded chitosan microspheres for nasal antiemetic drug delivery: an alternative approach to oral and parenteral routes

Background: The aim of this study was to develop chitosan microspheres for nasal delivery of ondansetron hydrochloride (OND). Method: Microspheres were prepared with spray-drying method using glutaraldehyde as the crosslinking agent. Microspheres were characterized in terms of morphology, particle size, zeta potential, production yield, drug content, encapsulation efficiency, and in vitro drug release. Results: All microspheres were spherical in shape with smooth surface and positively charged. Microspheres had also high encapsulation efficiency and the suitable particle size for nasal administration. In vitro studies indicated that all crosslinked microspheres had a significant burst effect, and sustained drug release pattern was observed until 24 hours following burst drug release. Nasal absorption of OND from crosslinked chitosan microspheres was evaluated in rats, and pharmacokinetic parameters of OND calculated from nasal microsphere administration were compared with those of both nasal and parenteral administration of aqueous solutions of OND. In vivo data also supported that OND-loaded microspheres were also able to attain a sustained plasma profile and significantly larger area under the curve values with respect to nasal aqueous solution of OND. Conclusion: Based on in vitro and in vivo data, it could be concluded that crosslinked chitosan microspheres are considered as a nasal delivery system of OND.     

Preparation of curcumin-hydroxypropyl-β-cyclodextrin inclusion complex by cosolvency-lyophilization procedure to enhance oral bioavailability of the drug

Abstract

The curcumin (CUR)-hydroxypropyl-β-cyclodextrin (HP-β-CD) inclusion complex (CUR-HP-β-CD) was prepared to erase its therapeutic restrictions of poor aqueous solubility and low oral bioavailability. CUR-HP-β-CD was prepared by a simple procedure of water-ethanol cosolvent incubation-lyophilization which may be suitable for scale up production, and characterized by Fourier transform-infrared spectroscopy (FT-IR), powder X-ray diffractometry (PXRD), differential scanning calorimetry (DSC), phase solubility method and dissolution study; the in vitro cytotoxicity was assayed by MTT, whereas the in vivo pharmacokinetics was tested by HPLC in rats receiving formulations via intravenous and oral administration, respectively. CUR was successfully encapsulated in HP-β-CD with a loading capacity of about 1:7 of CUR to HP-β-CD mole ratio, which remarkably enhanced drug water solubility and maintained well the antitumour activity of CUR. The CUR-HP-β-CD and free CUR have a similar pharmacokinetic behaviour in rats after intravenous administration; however, the oral bioavailability of CUR was enhanced to 2.77-fold by the HP-β-CD. The CUR-HP-β-CD can be successfully prepared by a simple method, which may be feasible for industrial scaling up, to remarkably increase drug water solubility and oral bioavailability while maintaining its bioactivity and may be a promising therapeutic preparation.     

核-壳结构磁性复合微球的制备与表征

通过分散共聚制得了聚(丙烯酸-丙烯腈-苯乙烯)(PAAS)三元共聚物微球,调整聚合反应介质乙醇与水的体积比及分散剂的用量,可将PAAS微球的粒径控制在230～680nm的范围内;扫描电子显微镜观察发现,所得微球粒径具有较好的单分散性.以该PAAS共聚物微球为载体,在二价和三价铁盐存在的条件下控制体系的pH,经共沉淀将Fe_3O_4纳米颗粒有效沉积在微球表面,得到了以PAAS为核,Fe_3O_4为壳的核-壳结构磁性复合微球;热重分析结果表明,复合微球上Fe_3O_4的含量达41%,对磁场具有明显的响应性.     

蔗糖/水体系磁性聚苯乙烯微球的制备及其表征

以氧化法制备Fe_3O_4磁流体,首次采用蔗糖水溶液为分散介质,以聚乙烯醇为稳定剂,偶氮二异丁腈为引发剂,悬浮聚合法合成了磁性聚苯乙烯微球.该蔗糖水反应体系对环境无污染且后处理简单.考察了蔗糖、苯乙烯(St)、Fe_3O_4磁流体、稳定剂、引发剂的含量等条件对微球的粒径及其分布的影响.所合成的磁性聚苯乙烯微球具有核壳型结构,有较强的磁响应性能,球形和分散度良好,粒径为80～85μm.采用红外光谱、振动样品磁强计和光学显微镜对磁性聚苯乙烯微球进行了表征.     

Evaluation of liposomal behavior in the gastrointestinal tract after oral administration using real-time in vivo imaging

Liposomes are regarded as promising drug carriers for enhancing the pharmacological effects of poorly absorbed drugs, such as peptides, following oral administration. Liposomal surface modifications by mucoadhesive polymers could improve drug absorption through interactions with the mucus layer. The main purpose of this study was to establish a method of monitoring the behavior of liposomes within the body after oral administration, particularly in the gastrointestinal (GI) tract, using a real-time in vivo imaging system (IVIS) to elucidate the behavior of surface-modified liposomes. Indocyanine green (ICG) was used as a near-infrared dye to label chitosan (CS) or glycol CS (GCS)-modified liposomes, and to observe the dynamic behavior of the liposomes in rats by noninvasive IVIS after oral administration. First, we validated IVIS results of the rat abdomens by comparing them to quantitative measurements of ICG fluorescence intensity in tissue homogenates. Nano-sized small unilamellar vesicles were retained longer than micro-sized multilamellar vesicles in the GI tract. Furthermore, surface-modified liposomes showed longer-term retention in the GI tract than unmodified liposomes in fasted rats. Moreover, surface modification by CS or GCS effectively prevented the excretion of liposomes from the GI tract and prolonged retention in fed rats.