阿立哌唑缓释微球的制备及体外释放特性的研究

目的 制备阿立哌唑聚乳酸-羟基乙酸共聚物(PLGA)缓释微球并考察其体外释放特性.方法 采用乳化-溶剂挥发法制备阿立哌唑缓释微球,通过正交试验优选最佳处方与制备工艺,并考察其载药量、包封率、粒径、形态和体外释放度.结果 所得微球的载药量为20.28％ ±0.38％,包封率为81.12％±0.02％,平均粒径为19.38 μm,形态圆整,30 d的体外累积释放度达88.73％.结论 所得阿立哌唑缓释微球形态圆整,载药量与包封率较高,具较好的缓释效果.     

丙氨瑞林微球制备工艺优化和体外释放研究

目的:制备包封率高、可持续释药35 d的丙氨瑞林微球.方法:以生物可降解聚合物聚乳酸-聚羟基乙酸(PLGA)为载体,采用W/O/W复乳溶剂挥发法制备缓释丙氨瑞林微球,以包封率为观察指标,用正交设计L9(34)对微球制备工艺进行优化.在pH=7.0的磷酸盐缓冲溶液中考察微球的体外释放.结果:经优化工艺制备的丙氨瑞林微球包封率为(93.2±1.6)％,90％的微球粒径分布范围为55～65 μm.在选择的释放条件下,至35 d时,药物累积释放92.3％,突释为9.7％.结论:该制备工艺简单、稳定.优化条件下制备的丙氨瑞林微球包封率高、粒径适宜、突释少.     

高分子材料对卡铂-乳酸/羟基乙酸共聚物微球体外性质的影响

目的:制备卡铂-乳酸／羟基乙酸共聚物(poly(lactic-co-glycolic acid),PLGA)微球,比较不同PLGA所得微球的体外释药特点。方法:采用乳化-溶剂挥发法制备卡铂-PLGA微球,显微镜下测定微球的粒径和粒径分布。采用电感耦合等离子体质谱(ICP-MS)测定微球含药量,计算包封率,考察微球体外释药行为。结果:PLGA来源和规格不同,对微球的形态、粒径、载药量和包封率没有明显影响,所得微球球形较好,平均粒径为38-54μm,含药量为6．4-7．2μg·mg-1,包封率16．3％-22．7％。药物体外释放行为随PLGA不同而有很大差异,PLGA 50／50微球突释快,突释率高。PLGA(50／50,η=0．18)和PLGA(50／50,η=0．53)的微球2 h药物突释率分别为55．06％和83．10％;PLGA(75／25,η=0．19)和PLGA(75／25,η=0.30)的微球12 h药物突释率分别为38．43％和44．04％。缓慢释放期PLGA(50／50,η=0．53)微球释药符合零级释放模型,其他3种材料的微球符合Higuchi释放方程,PLGA (50／50,η=0．18)和PLGA(75／25,η=0．19)微球体外较好地控制药物释放,缓释期药物释放速度常数分别为1．18和2.40 h-1/2。结论:PLGA来源和组成不同,制备的微球体外释药行为差异较大。PLGA(75／25,η=0．19)微球体外较好地控制卡铂的释放。     

聚乳酸聚乙醇酸微球体外突释的影响因素的研究

目的 考察几种影响干扰素α-2b聚乳酸聚乙醇酸(PLGA)微球体外释放突释的主要因素.方法 在复乳法的基础上结合海藻酸钠与钙离子螯合形成缓释凝胶的原理制备微球,研究海藻酸钠种类和浓度、PLGA黏度和浓度对微球突释的影响.结果 制备的微球形态圆整,结构致密,平均粒径范围为25～55 μm.微球的突释随着PLGA黏度或浓度...     

5-氟尿嘧啶控释植入剂在小鼠肿瘤组织的分布

目的 建立5-氟尿嘧啶(5-Fu)在小鼠肿瘤组织中的分析方法,并用于考察5-Fu控释植入剂在小鼠肿瘤组织的分布.方法 荷瘤小鼠瘤周植入分别由PLGA 50/50和PLGA 75/25为载体制备的5-Fu控释植入剂,RP-HPLC测定小鼠肿瘤组织中的药物浓度.结果 肿瘤组织中5-Fu的线性范围为0.5～15.4 μg·g-1,准确度为97.5％～ 104.0％,提取回收率为81.9％～88.3％,日内RSD均＜2.0％,日间RSD均＜7.6％.以PLGA50/50、PLGA75/25为载体的5-Fu控释植入剂在荷瘤小鼠体内的药动学参数:tmax分别为9、15 d;Cmax分别为3.79、2.83 μg·g-1; AUC分别为41.15、43.50 (μg·g 1)×d.结论 该分析方法可用于5-Fu在肿瘤组织中的分布行为研究,2种载体的5-Fu控释植入剂均能维持小鼠肿瘤组织中较长时间的药物分布,延长药效作用时间.     

GM-l PLGA微球的制备及其体外释药性质研究

目的制备GM l PLGA微球，考察其一般性质和体外释药特性。方法应用W/O/W乳化溶剂干燥法制备GM l PLGA微球，测定微球粒径、载药量、包封率和体外释药曲线。结果微球形态规则，粒径约为（18±8） μm，载药量约为4.9%，包封率约为61%，微球体外释药规律符合Higuichi方程：Q=0.153t1/2+0.037 05(r=0.995)。结论GM l PLGA微球的制备工艺良好，体外释药呈明显的缓释作用。     

乙交酯-丙交酯共聚物精制过程中有机锡的去除方法

在乙交酯-丙交酯共聚物(PLGA)精制过程中,比较了采用稀酸溶液和有机溶剂为萃取剂对聚合物中有机锡的去除效果,并考察了以有机溶剂为萃取剂时各工艺参数对精制效果的影响.结果表明,将PLGA溶于乙腈中配成1％的溶液后用等体积石油醚萃取3次,所得产品中锡残留量低于10 μg/g.该法能有效避免酸性条件下PLGA的降解,不使用无机酸.     

不同PLGA型号对奥曲肽微球的包封率和体外释放行为的影响

考察了不同型号聚乳酸-羟基乙酸共聚物(PLGA)作为水溶性药物奥曲肽微球载体对载药量、包封率和体外释放行为的影响.结果表明,PLGA中丙交酯含量降低,载药量和包封率降低,而突释量增大.PLGA型号相同时,黏度较大的PLGA微球载药量和包封率较高,突释量较小.采用PLGA与聚乳酸(PLA)混合材料制备的微球比单用PLGA材料微球的突释量小、载药量和包封率高、缓释效果好.     

人参皂苷Rg3 PLGA纳米粒的处方优化及制备工艺研究

目的为了提高人参皂苷Rg3的生物利用度和靶向性,以聚乳酸-羟基乙酸共聚物(PLGA)为载体材料,研究人参皂苷Rg3 PLGA纳米粒的处方和制备工艺。方法采用纳米沉淀法制备纳米粒,HPLC测定人参皂苷Rg3的含量。以包封率为指标,采用单因素和正交试验法优选处方和工艺。结果人参皂苷Rg3 PLGA纳米粒的最佳处方和工艺条件为:PLGA浓度为10 mg·m L-1,人参皂苷Rg3浓度为3 mg·m L-1,有机相与水相体积比为1:3。制备的纳米粒平均粒径为186.1 nm,包封率为87.29%。结论该工艺方法简便、稳定可行,适用于人参皂苷Rg3 PLGA纳米粒的制备。     

丹皮酚聚乳酸羟基乙酸微球的制备及体外释药考察

目的:制备丹皮酚聚乳酸羟基乙酸(PLGA)微球,考察其体外释药过程。方法:以丹皮酚为芯材,以PLGA为载体,采用乳化溶剂挥发法制备丹皮酚PLGA微球;以聚乙烯醇质量分数、PLGA质量浓度、药物与PLGA质量比及水油相体积比为考察因素,以包封率和载药量的综合评分为评价指标,采用正交试验优选制备工艺;扫描电镜和光学显微镜观察微球的外观和粒径,并测定其体外释药过程。结果:优选的工艺为聚乙烯醇质量分数0.9%、PLGA质量浓度60g/L、药物与PLGA质量比1∶3、水油相体积比1∶10。制得的微球球型规则,表面平滑,平均粒径为(31.75±0.13)μm。微球的载药量为(21.16±0.51)%,包封率为(66.91±1.62)%,8h体外累积释药量为37%。结论:所选工艺可用于制备丹皮酚PLGA微球,可为缓释药物传递系统的开发提供参考。     

Synthesis,Cytotoxicity and Antileishmanial Activity of Some N-(2-(indol-3-yl)ethyl)-7-chloroquinolin-4-amines

We report herein the condensation of 4,7-dichloroquinoline (1) with tryptamine (2) and D-tryptophan methyl ester (3) . Hydrolysis of the methyl ester adduct (5) yielded the free acid (6) . The compounds were evaluated in vitro for activity against four different species of Leishmania promastigote forms and for cytotoxic activity against Kb and Vero cells. Compound (5) showed good activity against the Leishmania species tested, while all three compounds displayed moderate activity in both Kb and Vero cells.     

Lung disease and PKCs

The lung offers a rich opportunity for development of therapeutic strategies focused on isozymes of protein kinase C (PKCs). PKCs are important in many cellular responses in the lung, and existing therapies for pulmonary disorders are inadequate. The lung poses unique challenges as it interfaces with air and blood, contains a pulmonary and systemic circulation, and consists of many cell types. Key structures are bronchial and pulmonary vessels, branching airways, and distal air sacs defined by alveolar walls containing capillaries and interstitial space. The cellular composition of each vessel, airway, and alveolar wall is heterogeneous. Injurious environmental stimuli signal through PKCs and cause a variety of disorders. Edema formation and pulmonary hypertension (PHTN) result from derangements in endothelial, smooth muscle (SM), and/or adventitial fibroblast cell phenotype. Asthma, chronic obstructive pulmonary disease (COPD), and lung cancer are characterized by distinctive pathological changes in airway epithelial, SM, and mucous-generating cells. Acute and chronic pneumonitis and fibrosis occur in the alveolar space and interstitium with type 2 pneumocytes and interstitial fibroblasts/myofibroblasts playing a prominent role. At each site, inflammatory, immune, and vascular progenitor cells contribute to the injury and repair process. Many strategies have been used to investigate PKCs in lung injury. Isolated organ preparations and whole animal studies are powerful approaches especially when genetically engineered mice are used. More analysis of PKC isozymes in normal and diseased human lung tissue and cells is needed to complement this work. Since opposing or counter-regulatory effects of selected PKCs in the same cell or tissue have been found, it may be desirable to target more than one PKC isozyme and potentially in different directions. Because multiple signaling pathways contribute to the key cellular responses important in lung biology, therapeutic strategies targeting PKCs may be more effective if combined with inhibitors of other pathways for additive or synergistic effect. Mechanisms that regulate PKC activity, including phosphorylation and interaction with isozyme-specific binding proteins, are also potential therapeutic targets. Key isotypes of PKC involved in lung pathophysiology are summarized and current and evolving therapeutic approaches to target them are identified.     

Gender-related symptoms and correlates of alcohol dependence among men and women with a lifetime diagnosis of alcohol use disorders

This study explored gender-related symptoms and correlates of alcohol dependence in a crosssectional study of 150 men and 150 women with a lifetime diagnosis of alcohol use disorders (AUD). Participants were recruited in equal numbers from treatment settings, correctional centres and the general community. Standardized measures were used to determine participants' use of substances, history of psychiatric disorders and psychosocial stress, their sensation seeking and family history of substance use and mental health disorders. Multivariate analyses were used to detect patterns of variables associated with gender and the lifetime severity of AUD. Men had a longer history of severe AUD than women. Women had similar levels of alcohol dependence and medical and psychological sequelae as men, despite 6 fewer years of AUD. More women than men had a history of severe psychosocial stress, severe dependence on other substances and antecedent mental health problems, especially mood and anxiety disorders. There were differences in family history of alcohol-related problems approximating same-gender aggregation. The severity of a lifetime AUD was predicted by its earlier age at onset and the occurrence of other disorders, especially anxiety, among both men and women. The limitations in the generalizability of these findings due to sample idiosyncrasies are discussed.     

Biochemical and molecular characterisation of cubozoan protein toxins

Class Cubozoa includes several species of box jellyfish that are harmful to humans. The venoms of box jellyfish are stored and discharged by nematocysts and contain a variety of bioactive proteins that are cytolytic, cytotoxic, inflammatory or lethal. Although cubozoan venoms generally share similar biological activities, the diverse range and severity of effects caused by different species indicate that their venoms vary in protein composition, activity and potency. To date, few individual venom proteins have been thoroughly characterised, however, accumulating evidence suggests that cubozoan jellyfish produce at least one group of homologous bioactive proteins that are labile, basic, haemolytic and similar in molecular mass (42-46 kDa). The novel box jellyfish toxins are also potentially lethal and the cause of cutaneous pain, inflammation and necrosis, similar to that observed in envenomed humans. Secondary structure analysis and remote protein homology predictions suggest that the box jellyfish toxins may act as α-pore-forming toxins. However, more research is required to elucidate their structures and investigate their mechanism(s) of action. The biological, biochemical and molecular characteristics of cubozoan venoms and their bioactive protein components are reviewed, with particular focus on cubozoan cytolysins and the newly emerging family of box jellyfish toxins.     

Dose tolerability of chronically inhaled voriconazole solution in rodents

Invasive pulmonary aspergillosis (IPA) is a fungal disease of the lung associated with high mortality rates in immunosuppressed patients despite treatment. Targeted drug delivery of aqueous voriconazole solutions has been shown in previous studies to produce high tissue and plasma drug concentrations as well as improved survival in a murine model of IPA. In the present study, rats were exposed to 20 min nebulizations of normal saline (control group) or aerosolized aqueous solutions of voriconazole at 15.625 mg (low dose group) or 31.25 mg (high dose group). Peak voriconazole concentrations in rat lung tissue and plasma after 3 days of twice daily dosing in the high dose group were 0.85 ± 0.63 μg/g wet lung weight and 0.58 ± 0.30 μg/mL, with low dose group lung and plasma concentrations of 0.38 ± 0.01 μg/g wet lung weight and 0.09 ± 0.06 μg/mL, respectively. Trough plasma concentrations were low but demonstrated some drug accumulation over 21 days of inhaled voriconazole administered twice daily. Following multiple inhaled doses, statistically significant but clinically irrelevant abnormalities in laboratory values were observed. Histopathology also revealed an increase in the number of alveolar macrophages but without inflammation or ulceration of the airway, interstitial changes, or edema. Inhaled voriconazole was well tolerated in a rat model of drug inhalation.