复方姜黄微囊对高脂血症大鼠血清脂质及肝脏病理的影响

目的观察复方姜黄微囊的调血脂作用。方法高脂饲料喂食60只大鼠12周造模,大鼠形成高血脂和肝脏脂肪变性,期间9～12周大鼠给予不同剂量复方姜黄微囊后,检测大鼠血清脂质水平并做肝脏病理组织学检查。结果复方姜黄微囊能显著降低高脂血症大鼠血清TC、TG、LDL-c水平,提高HDL-c水平,降低肝脏TC、TG水平,减轻肝脏脂肪变性程度。显著提高LPL、HL等脂质代谢酶活性和增强SOD等抗氧化酶活性应该是复方姜黄微囊产生调脂效应的相关作用机制。结论复方姜黄微囊具有较好的调血脂作用。     

乳化-溶剂挥发法制备左旋多巴微囊

目的优选乳化-溶剂挥发法制备左旋多巴微囊的工艺。方法以乙基纤维素（EC）为囊材,以微囊的包封率、载药量、累积溶出百分率为指标,采用正交试验优选左旋多巴微囊乳化-溶剂挥发法制备工艺条件,并对优化工艺所得微囊进行质量检查。结果优选出的制备工艺为：囊材溶于二氯甲烷的比例为8％,囊材与药量比例为1：1,EC（10mPa／s）与EC（20mPa／s）的比例为1：3,验证试验表明优化工艺所制左旋多巴微囊微囊平均包封率为92．98％,载药量为46．74％,24h累积溶出百分率为81．07％。微囊外观圆整且无粘连现象,微囊的粒径范围为10-50μm,体外具有明显的缓释效果。结论该工艺操作简便,工艺条件稳定、合理、可行。     

Microencapsulation of cells and molecular therapy of type 1 diabetes mellitus: The actual state and future perspectives between promise and progress

The history of microencapsulation of live cells started with an idea of Thomas MS Chang in 1964, thereafter applied to isolated pancreatic islets by Anthony M Sun in 1980. The original aim was to provide isolated cells with an immune-protective shield, to prevent physical contact between the transplanted cells and the host’s immune system, with retention of the microcapsules’ biocompatibility and physical–chemical properties over time. In particular, this revolutionary approach essentially applied to islet grafts, in diabetic recipients who are not immunosuppressed, at a preclinical (rodents) and, subsequently, clinical level. Among the different chemistries potentially suitable for microencapsulation of live cells, alginic acid-based polymers, originally proposed by Sun, proved to be superior to all others in the following decades. In fact, only alginic acid-based microcapsules, containing allogeneic islets, ultimately entered pilot human clinical trials in patients with type 1 diabetes mellitus, as immuno-selectiveness and biocompatibility of alginic acid-hydrogels were never matched by other biopolymers. With problems related to human islet procurement coming into a sharper focus, in conjunction with technical limits of the encapsulated islet grafting procedures, new challenges are actually being pursued, with special regard to developing both new cellular systems – able to release immunomodulatory molecules and insulin itself – and new microencapsulation methods, with the use of novel polymeric formulations, under actual scrutiny. The use of embryonic and adult stem cells, within microcapsules, should address the restricted availability of cadaveric human donor-derived islets, whereas a new generation of newly-engineered microcapsules could better fulfill issues with graft site and long-term retention of biopolymer properties.     

Microencapsulation of acetaminophen into poly(L-lactide) by three different emulsion solvent-evaporation methods

Poly(L-lactide) (PLLA) microcapsules containing acetaminophen (APAP) were prepared by three emulsion solvent-evaporation methods including an O/W-emulsion method, an O/W-emulsion co-solvent method and a W/O/W-multiple-emulsion method. The average size and morphology of the microcapsules varied substantially among these three preparation methods. Various alcohol and alkane co-solvents were found to exert significant impact on the O/W-emulsion co-solvent method and a more lipophilic co-solvent such as heptane appeared to enhance drug encapsulation with an efficiency nearly double of the O/W-emulsion method. When a small amount of water was added as the internal aqueous phase in the W/O/W-multiple-emulsion method, the encapsulation efficiency was found nearly triple of that for the O/W-emulsion method. While having a higher encapsulation efficiency, the microcapsules prepared by the W/O/W-multiple-emulsion method had as good controlled release behaviour as those prepared by the O/W-emulsion method. The release kinetics of microcapsules prepared by the O/W-emulsion method and the O/W-emulsion co-solvent (alcohol) method fitted the Higuchi model well in corroboration with the uniform distribution of APAP in PLLA matrix, i.e. the monolithic type microcapsules. However, the release kinetics of microcapsules prepared by the O/W-emulsion co-solvent (alkane) method and the W/O/W-multiple-emulsion method fitted the first-order model better, indicating the reservoir type microcapsules.     

自组装阿霉素微囊肝动脉灌注对兔VX2肿瘤细胞代谢及凋亡的影响

目的:研究自组装阿霉素微囊肝动脉灌注对兔肝VX2肿瘤生长、代谢和凋亡的影响。方法:24只新西兰大白兔接种肝脏VX2肿瘤组织块,建立肝脏肿瘤模型。随机分为4组,每组6只。分别经肝动脉给予生理盐水(A组)、空白微囊(B组)、阿霉素4mg/kg(C组)和阿霉素微囊等效药物4mg/kg(D组)。治疗后1、3、5、7、10和14d分别以PET/CT显像测定肿瘤体积、生长率及标准化摄取值(SUVmax)。处理后14d处死动物,常规病理、HE染色观察,DNA缺口末端标记(TUNEL)法检测肿瘤的凋亡指数,免疫组化测定肿瘤细胞增殖核抗原(PCNA)的表达。结果:治疗7d后给药组肿瘤体积及生长率明显降低,与空白微囊组及对照组有显著性差异(P<0.05),10d后阿霉素微囊组肿瘤呈负增长,生长率<100%,与其他各组有明显差异(P<0.05)。给予药物后,C、D组糖代谢水平降低,SUVmax值与A、B两组相比具有显著性差异(P<0.05),其中阿霉素微囊组SUVmax值呈持续下降趋势,10d后糖代谢水平明显低于其它组,肿瘤组织活力明显降低(P<0.05)。治疗14d后,阿霉素微囊组肿瘤细胞凋亡指数大于其它组,而增殖指数低于其它组(P均<0.05)。结论:自组装阿霉素微囊作为一种新型智能化供药体系,肝动脉灌注后可明显抑制兔肝脏VX2肿瘤生长,诱导肿瘤细胞凋亡,抑制肿瘤糖代谢和细胞增殖而发挥抗肿瘤效应,可有效提高肝脏肿瘤的化疗效果。     

甲壳胺-白及胶缓释微囊的研制

目的：以甲壳胺-白及胶混合作为囊材料，以甲硝唑为芯料制备微囊，研究其释药性。方法：改变微囊材料甲壳胺和白及胶的配比，测定药物在水中的溶出度。结果：甲壳胺中混有白及胶后改善了甲壳胺囊材的水溶性，且随着白及胶比例的增加，药物释放速度加快。结论：甲壳胺-白及胶混合作为囊材料制备微囊是可行的，调整甲壳胺和白及胶的配比，可改变微囊的缓释性能。     

The preparation and drug-release behaviour of CTA/EC and PMS/EC composite microcapsules

A cellulose triacetate (CTA) and three different molecular weights of poly(alphamethyl styrene) (PMS) were used as co-wall materials to prepare composite microcapsules with ethylcellulose (EC). A non-solvent-addition phase-separation method was used. The core material was theophylline (TH) and the solvent-non-solvent pair was dichloromethane-n-hexane, and the drug-release rates of the microcapsules prepared from these two types of co-wall materials were compared. The effects of their phase-separation range on the properties of the microcapsules, such as particle size, release rate and the morphology of the microcapsules are also discussed. The release rate of microcapsules was also affected by the compatibility of the co-wall materials and the EC. The dissolution studies indicated that the drug-release time of CTA/EC and PMS/EC composite microcapsules was sustained to 10 and 3.5 times, respectively, in comparison with that for pure EC microcapsules.     

A novel method for preparation of Eudragit RL microcapsules

A novel technique for the preparation of Eudragit RL microcapsules is described. The technique is based on the principle of solvent evaporation. Diclofenac sodium is used as a model drug for encapsulation. A solution of drug and Eudragit RL dissolved in acetone-isopropyl alcohol (1:1) is sprayed in liquid paraffin. The microcapsules obtained were uniform and free flowing particles. The release rate was more sustained by increasing the polymer concentration. The experimental procedure promises a rapid and convenient method for the preparation of Eudragit RL-microcapsules.     

LITERATURE ALERTS

Microcapsules in the micrometer size range with walls of nanometer thickness are of both scientific and technological interest, since they can be employed as micro- and nano-containers. Liposomes represent one example, yet their general use is hampered due to limited stability and a low permeability for polar molecules. Microcapsules formed from polyelectrolytes offer some improvement, since they are permeable to small polar molecules and resistant to chemical and physical influences. Both types of closed films are, however, limited by their spherical shape which precludes producing capsules with anisotropic properties. Biological cells possess a wide variety of shapes and sizes, and, thus, using them as templates would allow the production of capsules with a wide range of morphologies. In the present study, human red blood cells (RBC) as well as Escherichia coli bacteria were used; these cells were fixed by glutardialdehyde prior to layer-by-layer (LbL) adsorption of polyelectrolytes. The growth of the layers was verified by electrophoresis and flow cytometry, with morphology investigated by atomic force and electron microscopy; the dissolution process of the biological template was followed by confocal laser scanning microscopy. The resulting microcapsules are exact copies of the biological template, exhibit elastic properties, and have permeabilities which can be controlled by experimental parameters; this method for microcapsule fabrication, thus, offers an important new approach for this area of biotechnology.     

Influence of polybutylcyanoacrylate nanoparticles and liposomes on the efficacy and toxicity of the anticancer drug mitoxantrone in murine tumour models

Abstract

Polybutylcyanoacrylate (PBCA) nanoparticles were prepared and loaded with mitoxantrone, a highly effective anticancer drug. The proportion of mitoxantrone bound to the particles was analysed to be about 15 per cent of the initial drug concentration with the incorporation method and about 8 per cent with the adsorption method. Selected nanoparticle formulations were tested in leukaemia-or melanoma-bearing mice after intravenous injection. Efficacy and toxicity of mitoxantrone nanoparticles were compared with a drug solution and with a mitoxantrone-liposome formulation (small unilamellar vesicles with a negative surface charge). Furthermore, influence of an additional coating surfactant, poloxamine 1508, which has been shown to change body distribution of other polymeric nanoparticles, was investigated. It was shown that PBCA nanoparticles and liposomes influenced the efficacy of mitoxantrone in cancer therapy differently: liposomes prolonged survival time in P388 leukaemia, whereas nanoparticles led to a significant tumour volume reduction at the B16 melanoma. Neither nanoparticles nor liposomes were able to reduce the toxic side-effects caused by mitoxantrone, namely leucocytopenia. A slight additional influence of the coating surfactant was observed with only one preparation.