基于甘露糖化脂质卷构建免疫细胞靶向疫苗佐剂-传递系统

目的 构建安全、稳定、免疫细胞靶向亚单位疫苗佐剂-传递系统。方法 以磷脂酰丝氨酸为材料,采用乳化冻干法制备甘露糖修饰脂质卷,作为包封抗原载体。结果 乳化冻干法制备脂质卷平均粒径为950纳米,呈杆状,对于模型抗原包封率为38%,能够保护抗原在室温条件下2周内结构完整,在中性溶液中48小时抗原释放低于42%,并能够有效将所包封物质传递入免疫细胞。结论 采用乳化冻干法制备的脂质卷能够有效包封抗原,并提高其稳定性及免疫细胞靶向性,是一种有效的亚单位疫苗佐剂-传递系统。     

黏膜疫苗传递系统的研究进展

黏膜疫苗能同时诱导系统和局部黏膜免疫应答,是预防感染性疾病最理想的一类疫苗.但黏膜疫苗存在两大障碍:抗原无效摄取和难以引发有效免疫反应.因此,研发新型黏膜疫苗传递系统必须要克服这些障碍.本文综述了黏膜免疫的作用机制、黏膜疫苗的特点及其传递系统的研究现状.     

新型佐剂疫苗药学研究的思考

新型佐剂以及新型佐剂疫苗逐渐成为疫苗研究领域的新热点,目前如采用新佐剂的人乳头状瘤病毒(HPV)疫苗、乙肝疫苗和带状疱疹疫苗等已通过临床研究证实具有较大突破,并获得全球多个国家批准上市。由于新型佐剂制备工艺及质量控制与传统的铝佐剂不同,因此对于新佐剂及新型佐剂疫苗的药学研究也存在一些特点。本文就新型佐剂疫苗的发展,结合各国监管机构的指导原则以及审评实践,对其药学研究共性问题进行了一些探索与思考。     

壳聚糖介导的靶向药物传递系统

目的:综述了以壳聚糖或其衍生物为基础的多种特殊靶向载体系统的研究现状。方法:以国内外近年有代表性的文献为依据,进行分析、整理和归纳。结果与结论:由于壳聚糖具有一些独特的物理和生物特性,并且通过修饰后增加了壳聚糖的一些性质,使其成为优良的药物载体,从而实现药物的靶向性。这一载体材料近年来逐渐受到重视,具有良好的开发和应用前景。     

前列腺癌主动靶向药物传递系统的研究进展

目的 介绍前列腺癌主动靶向药物传递系统的研究进展。方法 查阅近年来国内外相关文献,对前列腺癌作用靶点为基础的主动靶向药物传递系统进行总结和归纳。结果 以前列腺特异性抗原和前列腺特异性膜抗原等作为靶点,应用抗体、适体或者多肽靶向修饰的脂质体、胶束、纳米粒、前体药物传递系统,可以将药物有效传递到前列腺癌靶组织、靶细胞,提高抗肿瘤药物作用效果。结论 主动靶向前列腺癌的药物传递系统具有广阔的研究和应用前景。     

固体脂质纳米粒用于细胞毒性药物传递系统综述的研究进展

目的:介绍固体脂质纳米粒(SLN)用于细胞毒性药物传递系统以治疗癌症的情况。方法:依据文献综述SLN用于抗癌药物载体的原理、包载细胞毒性药物后可解决的主要问题、用于癌症治疗的未来研究方向。结果与结论:设计合理的SLN可利用实体瘤组织的高通透性和滞留效应达到被动靶向的目的;解决的主要问题有提高对水溶性抗癌化合物的包封率、改进药物的控释速率和释放程度、避免被网状内皮系统清除;未来的研究方向为细胞毒性药物与增敏剂的联合治疗、细胞毒性药物SLN的特异性靶向,以及用于肿瘤治疗的基因传递。     

自乳化药物传递系统的研究概况

目的:总结自乳化药物传递系统的研究概况.方法:对近期自乳化药物传递系统的形成机制、处方组成、体外质量评价及其在药剂学方面的应用进行介绍.结果与结论:自乳化药物传递系统对亲脂性和水难溶性的药物是一个非常有前景的新型载体系统.     

基于PAMAM复合脂质载体的分级肿瘤主动靶向给药系统的构建及其性质考察

目的采用薄膜分散法制备了具有肿瘤分级靶向和pH敏感释药功能的载阿霉素聚酰胺-胺复合脂质载体c[RGDyk]-PEG2000-PSL-[PAMAM G5.0-AC80-FITC5-FA5/DOX]并对其相关性质进行了考察。方法通过微柱离心法和荧光分光光度法(spectrofluorometry,SPF)测定了聚酰胺-胺复合脂质载体的载药量及包封率;分别利用透射电镜(transmission electron microscope,TEM)、动态光散射法(dynamic light scattering,DLS)和ξ电位分析仪对聚酰胺-胺复合脂质载体的形态、粒径和表面电位进行了表征;采用透析法分别考察了聚酰胺-胺复合脂质载体在pH=7.4和pH=6.5释放介质中的体外释放行为,以及血浆对其体外释放行为的影响。结果聚酰胺-胺复合脂质载体的DOX包封率为35.17%(w),载药量为0.41%(w);其粒径分布很窄,平均粒径为106.1 nm;在透射电镜下,可见聚酰胺-胺复合脂质载体呈囊泡状,粒径大小均匀(100¹50 nm);其表面ξ电位值为-6.00 mV;聚酰胺-胺复合脂质载体的体外释药行为体现出pH敏感性和对血浆的稳定性。结论以c[RGDyk]-PEG修饰的pH敏感长循环脂质体包载PAMAM G5.0-AC80-FITC5-FA5/DOX复合物构建具有肿瘤分级靶向和pH敏感释药功能的载阿霉素聚酰胺-胺复合脂质载体有可行性及良好的应用前景。     

核-壳结构的脂质-聚合物杂化纳米粒的研究进展

核-壳结构的脂质-聚合物杂化纳米粒（CSLPHNs）是以具有生物可降解性的聚合物纳米粒为核,外层包覆单层或多层具有生物膜仿生性的脂质壳而形成,结合了纳米粒和脂质体的双重优点,具有粒径小、载药量高、生物相容性好及缓控释给药等优势,在药物递送系统中应用甚广。笔者在查阅近年国内外文献的基础上归纳了CSLPHNs的基本特性、制备方法及在眼部给药、肿瘤治疗及临床诊断成像中的最新研究进展。     

甘草次酸修饰肝靶向药物传递系统的研究进展

目的介绍甘草次酸修饰肝靶向药物传递系统研究进展,为该领域的深入研究和临床用药提供参考。方法查阅近5年国内外相关文献,对甘草次酸修饰的肝靶向药物传递系统进行归纳和总结。结果以甘草次酸受体为靶点,应用基于甘草次酸修饰的纳米药物传递系统(脂质体、纳米粒和聚合物胶束等)和甘草次酸-药物复合物将药物更有效地传递至肝组织、肝细胞中,提高抗肿瘤药物的作用效果。结论甘草次酸修饰肝靶向药物传递系统具有极大的研究价值和应用前景。     

脊髓灰质炎灭活疫苗和减毒活疫苗联合接种效果分析

目的：探讨脊髓灰质炎灭活疫苗（IPV）和减毒活疫苗（OPV）不同联合接种方式的临床效果。方法本研究为队列研究,将2009~2013年内收集的在管辖区域具备进行计划免疫4个部门的2400例新生儿进行随机分组,其中一组进行1剂IPV和2剂OPV序贯（I-O-O）（A组）,另一组2剂IPV和1剂OPV序贯（I-I-O）（B组）,并观察两组新生儿进行接种后的反应。结果这两种方式对于新生儿计划免疫无明显的差异。结论这两种方式对于新生儿进行脊髓灰质炎的计划免疫无不良反应。     

Tracking vaccine lot lifecycles using reports to the vaccine adverse event reporting system (VAERS)

PURPOSE: There is currently no systematically available information available on how rapidly a specific lot of vaccine is used once distributed. We used data from reports to the Vaccine Adverse Event Reporting System (VAERS) to develop a proxy means of surveillance for the lifecycle of selected vaccine lots. METHODS: A convenience sample, consisting of selected lots of: diphtheria, tetanus, and acellular pertussis (DTaP), Haemophilus influenzae type b (Hib), Hepatitis B, and varicella vaccines, was selected for lifecycle analysis. Assuming that circulation of a vaccine lot is proportional to vaccine-specific adverse event (AE) reporting for that vaccine type, we constructed Gamma distributed usage models and compared them with lot-specific VAERS reports to estimate the actual lifecycle of lots in the system. RESULTS: Evidence of lot circulation was detected within 1-2 months, and a peak was observed 3-4 months after the vaccine release date for most of the study vaccines. Ninety percent of the vaccine doses in each lot were estimated to be used within 5-9 months of distribution. The length of time a vaccine lot was in use ranged from 5 to 17 months from earliest vaccination date. CONCLUSIONS: Our modeled and inferred administration of the selected lots of different vaccines were concordant. This method may be useful for spatial and temporal tracking of vaccine lot utilization.     

23价肺炎球菌疫苗联合流感疫苗对COPD急性发作的临床干预

目的观察23价肺炎球菌疫苗与流感疫苗联合使用对COPD急性发作的临床疗效。方法将本社区COPD患者69例,随机分为疫苗组（36例）与对照组（33例）。对疫苗组所有接种对象疫苗接种后进行随访2周,监测不良反应,同时对研究对象进行跟踪随访1年,并从COPD急性发作的次数、天数、发作间距、住院次数、平均住院天数、病情严重程度、死亡率等方面进行对比。结果疫苗组COPD急性发作的次数和程度较对照组明显较少,差异有统计学意义（P〈0．05）。疫苗组偶有局部不良反应,对症治疗后8～24小时均能自行缓解。结论联合接种23价肺炎球菌疫苗与流感疫苗对COPD急性发作具有明显的干预效果,不良反应可以耐受,值得临床推广。     

第一代无细胞百日咳疫苗毒性国家参考品制备工艺的研究

目的筛选无细胞百日咳疫苗毒性国家参考品的最佳生产工艺。方法选用百日咳CS菌株(编号58003),对不同的培养方式进行比较研究,选择最佳毒性国家参考品的生产工艺。结果该参考品经过不同培养方式比较后,确定了最终生产工艺,将培养的百日咳菌加入保护剂后分装制备成冻干品。结论该生产工艺制备的样品含有较强的毒性,同时能进行规模生产,满足了毒性国家参考品各项检测指标的要求。     

Zoster vaccine live

Herpes zoster is a neurocutaneous disease caused by the varicella-zoster virus and is associated with significant morbidity and long-term sequelae in older adults. Until recently, treatment options for these complications have been primarily targeted at disease state management and symptom relief. Zoster vaccine live is the first vaccine approved for the prevention of herpes zoster. The vaccine was approved by the United States Food and Drug Administration for adults aged 60 years or older. Results of the Shingles Prevention Study demonstrated that in older individuals, administration of zoster vaccine live reduces the burden of illness associated with herpes zoster by 61.1%, the frequency of herpes zoster pain and discomfort by 51.3%, and the frequency of postherpetic neuralgia by 66.5%. Overall, adverse events reported in clinical trials of zoster vaccine live were classified as mild. Events that occurred more frequently in zoster vaccine live recipients than in placebo recipients included injection site reactions, headache, respiratory infections, fever, flu syndrome, diarrhea, rhinitis, skin disorders, respiratory disorders, and asthenia. The Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices recently recommended universal vaccination for those 60 years of age and older, including those who have experienced previous episodes of shingles.     

Squalane-based emulsion vaccine delivery system: composition with murabutide activate Th1 response

Emulsions play an important role in present-day subunit vaccine delivery. Squalane-based emulsion was formulated using surfactants viz., Pluronic F68, Span 85 along with Murabutide (MB) as immunepotentiator. Particle size and zetapotential of the final optimized emulsion was found to be 134?nm and ?13?mV, respectively. The in vitro cellular uptake studies performed using fluorescein isothiocyanate (FITC)-labeled ovalbumin (OVA) clearly revealed the rapid uptake of antigen in the presence of emulsion. The in vivo subcutaneous studies involving measurement of OVA-specific IgG antibody titers, Th1/Th2 cytokines were performed and a marked up regulation in IL-2, IL-12 and IFN-γ cytokines indicate Th1 immune response. Results supported that the squalane-based delivery system enhanced the uptake of the antigen by immune cells and elicited humoral as well as cell-mediated immune response in mice. These results indicate the promising application of the new squalane based oil-in-water (O/W) emulsion as capable vaccine delivery system useful for vaccine development.     

肿瘤的多肽疫苗

肿瘤疫苗是目前肿瘤生物治疗的有效方法之一,用肿瘤抗原多肽作为肿瘤疫苗具有一定的优越性。多肽疫苗在临床试验中已取得了一定的效果,如和树突状细胞联合应用可以提高其免疫效果,但在临床应用中也应注意避免自身免疫的发生。