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近二十年来 ,生物技术药物 (biotechdrugs)的发展突飞猛进 ,已日益受世人瞩目。其中生物技术疫苗迅速增加 ,用于癌症、艾滋病、类风湿性关节炎、镰刀形贫血、骨质疏松症、乙型肝炎及其它感染性疾病[1] 。但这类药物在口服时存在生物利用度低、物理化学稳定性差、体内半衰期短等缺点 ,致使它们常常只能采用频繁地注射给药 ,其使用与保存十分不便。口服疫苗微球则是一种有效的新制剂 ,它能满足人们对给药次数最少的需要 ,并可实现在膜表面的诱导免疫。国内对口服疫苗微球研究较少 ,本文从口服疫苗微球的特点、制备与体外释放、胃… 相似文献
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壳聚糖是一种被广泛应用的天然聚合物,其特殊的物理化学性质和生物特性为口服疫苗微球载体的研究提供了一条新途径,壳聚糖在口服疫苗呈递中有广阔的应用前景。此文就壳聚糖微球作为口服疫苗载体的应用进行综述。 相似文献
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可生物降解微球作为口服疫苗载体的研究进展 总被引:4,自引:0,他引:4
龚非 《国外医学(预防.诊断.治疗用生物制品分册)》2000,23(5):211-215
本文主要介绍可生物降解微球作为口服疫苗载体的优越性,以及微球疫苗的制备工艺、体外释放动力学、口服后的体内分布、免疫机理、口服质粒DNA微球疫苗的研究进展。 相似文献
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本文主要介绍可生物降解微球作为口服疫苗载体的优越性 ,以及微球疫苗的制备工艺、体外释放动力学、口服后的体内分布、免疫机理、口服质粒 DNA微球疫苗的研究进展 相似文献
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胰岛素肠溶微球口服的实验研究 总被引:7,自引:1,他引:6
目的 :研制一种可供口服的胰岛素肠溶微球。方法 :采用相分离法制备胰岛素丙烯酸树脂微球 ;建立放射性免疫法测定微球包封率 ;利用体外实验法考察微球的抗酸及肠溶能力 ;将不同处方的微球给大鼠灌胃 ,测定其血糖变化。结果 :制得微球粒径分布在 2~ 7μm ;包封率 95 .17% ;在人工胃液中 2h有少于 14%的胰岛素释放 ;在人工肠液中 1h内胰岛素的释放度达 96 % ;微球可使大鼠产生明显的降血糖效果。结论 :胰岛素口服肠溶微球是一类具有发展前景的制剂。 相似文献
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黄维金 《国际生物制品学杂志》2007,30(4):186-187
印度皮革研究所Rajkannan等将代表HBsAg B细胞表位127-145残基的多肽(BCEP)包裹人丙交醋、乙交醋共聚物( PLG)作为口服乙型肝炎疫苗进行了研究。通过W/O/W双乳剂-溶剂燕发法制备BCEP的PLG微球(BCEM),平均直径10μm,BCEP包裹效率为64%。体外释放研究结果 相似文献
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Synthesis and Antiviral Activity of Novel Phosphorylated Derivatives of Didanosine Against Newcastle Disease Virus in Chicken
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Karanam Anandan Suresh Venkata Subbaiah C. Kadiam Thaslim S. K. Basha Naga Raju Chamarti Suresh M. Kumar Rajendra Wudayagiri Lokanatha Valluru 《Archiv der Pharmazie》2016,349(6):442-455
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Virosome and ISCOM vaccines against Newcastle disease: preparation, characterization and immunogenicity 总被引:4,自引:0,他引:4
Atthachai Homhuan Sompol Prakongpan Prachak Poomvises Riks A Maas Daan J.A Crommelin Gideon F.A Kersten Wim Jiskoot 《European journal of pharmaceutical sciences》2004,22(5):1657-468
The purpose of this study was to prepare and characterize virosomes and ISCOMs containing envelope proteins of Newcastle disease virus (NDV) and to evaluate their immunogenicity in target animals (chickens). Virosomes were prepared by solubilization of virus with either Triton X-100 or octyl glucoside (OG) followed by detergent removal. Biochemical analysis revealed that these virosomes contained both the haemagglutinin-neuraminidase protein (HN) and the fusion protein (F), with preserved biological activity. Acidic environment triggered the fusion between virosomes and chicken erythrocyte ghosts. Formation of ISCOMs was achieved by solubilizing phospholipids, cholesterol, envelope protein antigen and Quil A in Triton X-100. The ISCOM particles were formed by removal of the detergent. In each formulation the relative HN content correlated with the capability to agglutinate red blood cells. The immunogenicity of these lipid-based subunit vaccines was determined in chickens after subcutaneous immunization. The relative HN content of the subunit vaccines correlated with the haemagglutination-inhibition (HI) antibody titres. Virosomes prepared with Triton X-100 and ISCOMs offered high clinical protection (> 80%) upon challenge with virulent NDV. Virosomes prepared with OG yielded lower clinical protection despite high HI antibody titres. Virosomes with reduced antigen density showed poor immunogenicity and protection. In conclusion, ND virosomes and ISCOMs were found to be immunogenic and provided good protection. 相似文献
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Oral Immunization of Rats with Proteinoid Microspheres Encapsulating Influenza Virus Antigens 总被引:1,自引:0,他引:1
Santiago Noemi Milstein Sam Rivera Theresa Garcia Elisa Zaidi Tabassum Hong Hyunki Bucher Doris 《Pharmaceutical research》1993,10(8):1243-1247
Influenza virus antigen microspheres were prepared by a pH-dependent process using a protein-like polymer (proteinoid) made by thermal condensation of amino acids. The efficacy of these preparations to induce specific IgG responses when used as oral vaccines in rats was evaluated. A single enteric dose of Ml entrapped in proteinoid microspheres was able to induce a significant IgG response to Ml as early as 2 weeks postdosing, while rats dosed orally with the same Ml total dose (no microspheres) showed no detectable antibody response. An unencapsulated hemagglutinin and neuraminidase (HA-NA) preparation induced a moderate anti HA-NA IgG response. A single enteric dose of HA-NA spheres induced a response in 33% of the rats; this response was up to eight times higher than that observed in the rats dosed with unencapsulated antigen. 相似文献
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Uchida Takahiro Shiosaki Kouichi Nakada Yoichi Fukada Katsuhiko Eda Yasuyuki Tokiyoshi Sachio Nagareya Noriko Matsuyama Kenji 《Pharmaceutical research》1998,15(11):1708-1713
Purpose. To prepare poly(lactide-co-glycolide)(PLGA) microspheres containing recombinant hepatitis B core antigen (HBcAg; Mw = 3,600,000) by a w/o/w emulsion/solvent evaporation method and evaluate the possibility of this system as a potent long-acting carrier for hepatitis B core antigen in mice.
Methods. Various additives had been incorporated in the internal aqueous phase during the process of microencapsulating HBcAg, HBcAg antigenicity in the medium extracted from the prepared microspheres were measured by ELISA. Shape confirmation of the HBcAg antigen was performed by a sucrose gradient velocity centrifugal technique. For in vivo study, prepared microspheres were administered subcutaneously to Balb/C mice, and the serum IgG level was determined by ELISA.
Results. The inactivation of HBcAg by methylene chloride was dramatically reduced by the addition of gelatin (4–8% (w/v)) to the internal aqueous phase during the preparation. Further improvement of the loading efficiency to almost 61% resulted with cooling (4°C). The prepared microspheres (4.27 m ± 1.23 m) containing 0.15% HBcAg displayed burst release (50–60% within 2 days). In subcutaneous inoculation, the adjuvant effect of PLGA microspheres was almost the same as that of the complete Freund's adjuvant. Whereas oral inoculation using the microspheres was not effective.
Conclusions. The pH of the added gelatin seemed to be the key to the stabilization of HBcAg from various stability tests and CD spectrum study. Finally, the possibility of using this system as a potent long-acting hepatitis B vaccine was demonostrated. 相似文献
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Alonso Maria J. Cohen Smadar Park Tae G. Gupta Rajesh K. Siber George R. Langer Robert 《Pharmaceutical research》1993,10(7):945-953
Controlled-release formulations based on poly(lactic) (PLA) and poly(lactic/glycolic) acid (PLGA) microspheres containing tetanus vaccine were designed. The polymers forming the microspheres were L-PLA of different molecular weights and DL-PLGA, 50:50. These microspheres were prepared by two solvent elimination procedures, both using a double emulsion, and were characterized for size, morphology, and toxoid release kinetics. The influence of formulation variables such as polymer type, vaccine composition, and vaccine/polymer ratio was also investigated. Both techniques yielded microspheres with similar size, morphology, and release properties. Microsphere size was dependent on the type of polymer and the presence of the surfactant L--phosphatidylcholine, which led to a reduction in microsphere size. On the other hand, the release kinetics of encapsulated protein were affected by the polymer properties (ratio lactic/glycolic acid and molecular weight) as well as by the vaccine composition, vaccine loading, and microsphere size. Moreover, for some formulations, a decrease in microsphere size occurred simultaneously, with an increase in porosity leading to an augmentation of release rate. The changes in the PLA molecular weight during in vitro release studies indicated that release profiles of tetanus toxoid from these microspheres were only marginally influenced by polymer degradation. A significant fraction of protein (between 15 and 35%) was initially released by diffusion through water-filled channels. In contrast, the decrease in the PLGA molecular weight over the first 10 days of incubation suggested that erosion of the polymer matrix substantially affects protein release from these microspheres. Among all formulations developed, two differing in microsphere size, polymer hydrophobicity, and release profile were selected for in vivo administration to mice. Administration of both formulations resulted in tetanus neutralizing antibody levels that were higher than those obtained after administration of the fluid toxoid. 相似文献
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目的:制备麻疹病毒抗血清,用于含麻疹病毒成分的联合减毒活疫苗的检定。方法:制备麻疹病毒Edm-3株病毒收获液,加入弗氏佐剂,对家兔和豚鼠分别经皮下多点或腹腔途径免疫3针,采血制备抗血清,经除菌过滤和补体灭活后,对抗血清进行中和效价、中和能力、细胞毒性及特异性检测。结果:用4种免疫方式制备的抗血清中和效价均高于1∶320... 相似文献
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S. M. Sivakumar N. Sukumaran R. Murugesan T. S. Shanmugarajan J. Anbu L. Sivakumar B. Anilbabu G. Srinivasarao V. Ravichandran 《Indian journal of pharmaceutical sciences》2008,70(4):487-490
The present study was aimed to replace the alum type adjuvant for hepatitis B vaccine. The hepatitis B vaccine was encapsulated in poly (DL-lactide-co-glycolide) microspheres by solvent evaporation technique. The formulated microspheres were characterized in terms of morphology, particle size analysis, in vitro release study and in vivo immune response in male Wistar rats. The FT IR spectrum illustrates the characteristics bands of poly (DL-lactide-co-glycolide) microspheres and hepatitis B vaccine at 1750 cm-1 and 1650 cm-1, respectively. The hepatitis B vaccine loaded poly (DL-lactide-co-glycolide) microspheres were able to release antigens till day 42. Significant enhancement of specific antibodies to HBsAg was produced till day 90 after a single administration of HBsAg encapsulated poly (DL-lactide-co-glycolide) microspheres. However, the conventional alum adsorbed hepatitis B vaccine was not found to produce any significant specific antibody levels till day 90 after a single dose. The results showed that poly (DL-lactide-co-glycolide) microspheres show potential as an adjuvant for hepatitis B vaccine. 相似文献
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Uchida Takahiro Martin Stephen Foster Todd P. Wardley Richard C. Grimm Susan 《Pharmaceutical research》1994,11(7):1009-1015
Poly(lactide-co-glycolide) microspheres containing different loads of OVA (0.05, 0.1, 0.5 and 1.0% w/w) were manufactured by a w/o/w emulsion/solvent evaporation method. Low load efficiencies of less than 20% were observed. Normal size distributions with mean volume diameters ranging from 3.7 to 4.7 µm were obtained for different batches. The in vitro release of OVA from different loaded microspheres showed an expected burst release with all batches. The in vivo dose study (1, 10, 25, 50 µg of OVA) was performed by subcutaneous and oral inoculation in mice by single (0 week) or double (0 and 3 weeks) administration of PLGA 50/50 microspheres containing 0.1% OVA. Subcutaneous administration showed an immune response (serum Ig levels by ELISA) statistically (Fishers paired t-test; P < 0.05) above OVA saline negative controls at 3, 6 and 12 weeks after administration. Oral administration of microspheres produced statistically higher systemic immune responses at the higher doses. Single and double inoculation orally and subcutaneously produced similar serum antibody levels. The in vivo load study was performed by subcutaneous and oral administration to mice of 25 µg OVA contained in various loaded (0.05, 0.1, 0.5 and 1.0% w/w) microspheres. Serum immune responses at 3, 6, and 12 weeks after inoculation were statistically above OVA saline controls and were inversely proportional to the OVA load using either route. This observation suggested a relationship between the number of microspheres delivered and the in vivo serum response. Single subcutaneous administration of 0.05 or 0.1% OVA loaded PLGA 50/50 microspheres induced larger immune responses compared with complete Freunds adjuvant. 相似文献