苦参碱纳米柔性脂质体的制备及包封率测定

目的制备苦参碱纳米柔性脂质体并测定其包封率,并与苦参碱普通脂质体比较。方法以1,2-丙二醇为膜柔软剂,用薄膜分散法制备苦参碱纳米柔性脂质体,采用激光粒度分布仪和透射电子显微镜考察其药剂学性质,采用葡聚糖凝胶G-50分离脂质体,并用高效液相色谱(HPLC)法测定其对苦参碱的包封率。结果苦参碱纳米柔性脂质体的外观为椭球形或圆球形,粒径为219.2 nm,表面电位为-48.5 m V,其包封率(80.48±1.82)%是普通脂质体(50.79±2.24)%的1.58倍。结论薄膜分散法制备的纳米柔性脂质体与普通脂质体相比,对苦参碱具有更好的包封效果,而且稳定性较理想,可作为苦参碱的一种新型给药载体。     

苦参碱固体脂质纳米粒的构建及包封率测定方法研究

目的制备苦参碱固体脂质纳米粒并进行质量评价;利用不同方法测定苦参碱固体脂质纳米粒的包封率,建立其包封率测定方法。方法以微乳-探头超声法制备固体脂质纳米粒并对其粒径、电位、微观形态、体外释放等进行质量评价;建立苦参碱HPLC含量测定方法;分别采用葡聚糖凝胶法、低温超速离心法、超滤法、透析法测定苦参碱固体脂质纳米粒的包封率,比较各个方法的优点和缺点,筛选并建立有效测定包封率的方法。结果苦参碱固体脂质纳米粒粒径为(116. 7±2. 6) nm,Zeta电位为(-45±1. 7) m V,透射电镜照片显示固体脂质纳米粒大小均一,形状为球形;体外释放结果显示,纳米粒呈现一定程度的缓释特点;葡聚糖凝胶微柱离心法能有效分离游离药物和固体脂质纳米粒,所测得的包封率数据稳定差异小。结论本实验成功制备苦参碱固体脂质纳米粒,并对其粒径、电位和体外释放进行了质量评价;建立的葡聚糖凝胶微柱法为水溶性药物固体脂质纳米粒的包封率测定提供可靠参考。     

麻黄碱壳聚糖修饰脂质体凝胶剂的制备及体外透皮研究

目的制备麻黄碱壳聚糖修饰脂质体凝胶剂,考察其粒径分布、包封率及体外透皮特性。方法采用薄膜蒸发法制备麻黄碱脂质体混悬液,在麻黄碱脂质体混悬液中缓慢滴加pH值为5～6的0.35%壳聚糖溶液,制成麻黄碱壳聚糖修饰脂质体凝胶剂。激光粒度仪测定修饰脂质体的粒径分布,反透析法测定包封率,Franz扩散装置考察其体外透皮特性。结果麻黄碱壳聚糖修饰脂质体的平均粒径在1 400～1 900 nm;平均包封率达(41±0.94)%;修饰脂质体中麻黄碱能缓慢透过大鼠皮肤,与普通剂型相比累积透过量随时间变化差异较明显,缓释效果显著。结论该制剂制备工艺简单,性质稳定,药物包封率较高,定量测定方法简便、准确;药物透皮速率缓慢,释药稳定。     

苦参总生物碱脂质体凝胶的制备及释药机制研究

目的优化苦参总生物碱脂质体的处方与工艺,制备苦参总生物碱脂质体凝胶并研究其释放机制。方法运用薄膜分散法制备苦参总生物碱脂质体,以包封率和载药量为考察指标,采用酸性染料比色法测定脂质体中苦参碱含量。采用正交试验设计对处方工艺进行优化,选出最优处方制备脂质体。以泊洛沙姆-407为基质,制备苦参总生物碱脂质体凝胶。考察药物凝胶与药物脂质体凝胶的透皮速率。结果通过优化处方与工艺所得的脂质体形态均匀,粒径范围为100~400 nm,包封率达74%,载药量达26%。所制备的脂质体凝胶呈透明状半固体。体外释放结果显示,苦参碱凝胶48 h内累积释药量为6.34 mg/cm~2,苦参总生物碱脂质体凝胶48 h内累积释药量为6.97 mg/cm~2,后者的累积透皮量、稳态透皮速率及48 h后在皮肤中的蓄积量均较前者显著提高。结论优化的制备工艺稳定可行,制得的苦参总生物碱脂质体凝胶质量较好,可有效延缓药物的释放速率,提高药物在体内的蓄积量。     

氧化苦参碱负电荷脂质体的制备及理化性质研究

 目的考察氧化苦参碱负电荷脂质体的处方和制备工艺,并研究其理化性质。方法以包封率为主要指标,对不同制备方法进行考察。采用逆相蒸发法制备,以均匀设计筛选优化最佳处方工艺,制备氧化苦参碱负电荷脂质体,并考察脂质体的形态、粒径、Zeta电位、包封率及体外释放度等理化性质。结果逆相蒸发法制备的脂质体在电镜下呈类圆形,粒径分布均匀,平均为253.6 nm,药物包封率为60.17%,Zeta电位为-40.5,体外释放用双指数方程拟合良好。结论氧化苦参碱负电荷脂质体包封率较高,带负电,粒径分布均匀,符合肝靶向要求。     

水溶性药物脂质体制备方法的研究进展

根据目前水溶性药物易泄漏、包封率低的不足,查阅近几年国内外相关文献,对其制备方法进行综述。总结水溶性药物脂质体制备方法的研究进展,为水溶性药物脂质体制备提供参考。脂质体包载水溶性药物在实验室研究中已取得不错的成果,但大工业生产较困难,还需深入研究。     

磺胺醋酰-氧氟沙星脂质体的制备及影响因素考察

目的 考察磺胺醋酰-氧氟沙星脂质体制备工艺中的各因素影响以及药物的抗菌活性.方法 采用薄膜分散-超声法制备磺胺醋酰-氧氟沙星脂质体,电子显微镜观察脂质体粒径,过滤法分离游离药物,紫外线(UV)测定包封率,微孔显色法测定其抗菌活性.采用单因素实验来考察脂质体成膜时水浴温度、水浴时间和磷脂比对脂质体包封率以及回收率的影响,...     

基于白及多糖的黄藤素纳米柔性脂质体膜剂的制备研究

目的以白及多糖(BSP)为成膜材料,制备黄藤素(PA)纳米柔性脂质体(PFL)膜剂,并评价其药剂学相关性能,为其进一步应用奠定基础。方法采用注入法制备黄藤素纳米柔性脂质体,匀浆涂布法制备黄藤素纳米柔性脂质体白及多糖膜剂(PFL-BPF);采用电子显微镜、差示扫描量热仪(DSC)和体外透黏膜实验等对PFL-BPF进行表征和评价。结果以BSP为成膜材料时,PFL与BSP的相容性良好且易于成膜;所得PFL-BPF的外观平滑、无气泡、柔韧性与挺度适宜;PFL-BPF具有良好的生物黏附性,黏附于黏膜后耐生理盐水冲刷时间为(130±7)min。PFL-BPF在0.5 h时,促进PA渗入黏膜的剂量为32.41μg/g,分别为黄藤素水溶液白及多糖膜剂(PL-BPF)、空白柔性脂质体+黄藤素白及多糖膜剂(BLP+PA-BPF)的3.17倍和1.9倍(t检验,P0.05);2.5 h,分别为PL-BPF、BLP+PA-BPF的2.67倍和1.89倍。表明其能够显著促进水溶性药物PA透过黏膜且缓释作用强;DSC显示其促进药物透黏膜吸收的可能机制为柔性脂质体扰乱黏膜上皮细胞紧密排列而携带药物进入黏膜组织。结论 PFL-BPF成膜性好、黏附作用持久、耐冲刷能力强,且制备工艺简单可行,能够显著地促进药物透过黏膜,因此,纳米柔性脂质体膜剂是一种良好的透黏膜给药载体,具有广阔的应用前景。     

苦参碱磁性脂质体的制备和表征的实验研究

目的:制备苦参碱药物磁性脂质体。方法:用正交实验确定适宜的工艺条件,采用逆相蒸发法制备苦参碱药物磁性脂质体;应用透射电镜、振动样品磁强计、高效液相色谱法等考察脂质体形态、磁性和包封率等。结果:制得苦参碱磁性脂质体外观形态、粒度分布良好,包封率高,磁场响应性和稳定性良好。结论:本工艺可靠易行,可制备性能优良的苦参碱。     

氮酮对白癜风脂质体软膏中补骨脂素透皮作用的影响

目的：探讨水溶性氮酮和脂溶性氮酮对白癜风脂质体软膏透皮吸收的影响。方法：配置含不同浓度的水溶性氮酮和脂溶性氮酮的白癜风脂质体软膏,采用Franz扩散池体外透皮试验,用高效液相色谱法测定补骨脂素和异补骨脂素透皮吸收量。结果：两种氮酮在2%-5%浓度范围内与空白组有显著性差异;经皮吸收量与时间呈正相关性;与氮酮浓度无相关性;水溶性氮酮组透过量高于相对应的脂溶性氮酮组。结论：氮酮在2%-5%范围内可增加白癜风脂质体软膏中补骨脂素的透过率。     

主动载药法制备苦参碱脂质体的研究

目的考察脂质体不同制备方法对包封率的影响。方法采用被动载药和主动载药制备脂质体,用微柱离心-紫外分光光度法测定脂质体包封率。结果被动载药法制备脂质体包封率较低,主动载药制备脂质体包封率为84.38%。结论采用硫酸铵梯度法可制得包封率较高的苦参碱脂质体。     

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??OBJECTIVE To prepare palmatine- loaded flexible nano-liposomes (PFNL) and study their pharmaceutical properties, in order to lay the foundation for the industral application. METHODS The flexible nano-liposomes were prepared by thin-film homogenization method with propyleneglycol (PG) as softening agent. The entrapment rate of palmatine was evaluated by protamine aggregation method and HPLC. The effects of concentrations of phosphatidylcholine (PSC), cholesterol (CH), and PG on the entrapment efficiency of palmatine were also investigated. The pharmaceutical properties of PFNL were evaluated by TEM, PCS and CLSM. The deformation of PFNL was determined by its relative rate of permeating the microporous filter membrane. The coagulation rate constant (K) was measured by constant temperature conductivity method. The side-by-side diffusion cells and pig vaginal mucosa were used to investigate the characteristics of the release of palmatine from PFNL in vitro, and the effects of PFNL on the expression of cytokines (SLPI, LF and SP-D) were investigated and compared with classic liposomes and lotion of palmatine. RESULTS The palmatine entrapment efficiency was (78??2.13)% when the PFNL were prepared with PSC (3%), CH (0.02%), and PG (20%). The prepared nano flexible liposomes had a closed spherical or elliptical shape and appeared as multi-lamellar vesicles under the TEM and CLSM.The calculated mean size was (185??19) nm, and the Zeta potential was (-53??2.27) mV. The deformation of PFNL was (79??5.75)%. The coagulation rate constant (K) of PFNL was always lower than that of traditional palmatine- loaded liposomes. The accumulated permeation amount of palmatine from the PFNL at 6.0 h was 1.53 and 2.86 folds of those of classic liposomes and lotion, respectively. Moreover, the expressions of cytokines (SLPI, LF and SP-D) in female SD rats after being treated with PFNL, PCL and PL were similar to that of the control group. CONCLUSION The prepared PFNL have high encapsulation efficiency, good stability and safety, and greatly increase the vaginal mucosa permeability of palmatine. Flexible nano-liposomes may be a useful drug delivery carrier for the gynecological application of palmatine.     

盐酸青藤碱纳米柔性脂质体的制备及其性质研究

目的制备盐酸青藤碱纳米柔性脂质体,探索其体外透皮给药的规律与机制。方法采用薄膜分散法制备以丙二醇为柔软剂的盐酸青藤碱纳米柔性脂质体,考察卵磷脂、胆固醇与丙二醇对脂质体包封率的影响;高效液相色谱(HPLC)法测定青藤碱的量,原子力显微镜(AFM)、透射电镜(TEM)和光子相关光谱仪(PCS)描述其物理性质。采用双室扩散池法研究其体外透皮给药规律,透皮给药结束后用扫描电镜(SEM)观察皮肤表面结构的变化。结果卵磷脂、胆固醇和丙二醇的质量分数分别为3%、0.02%、25%时,制备的柔性脂质体对盐酸青藤碱的包封率为(66±2.3)%;其外观为圆形或椭圆形,内部为多层囊泡结构,粒径为(170±26)nm,表面电位为-(43±3.4)mV。柔性脂质体能够使角质层结构变得紊乱无序,角质细胞间隙增大而提高皮肤对药物的渗透性。结论纳米柔性脂质体能够显著提高盐酸青藤碱透皮给药效果,可作为盐酸青藤碱透皮给药的新型纳米载体。     

PLGA-PEG-PLGA温敏水凝胶包载多柔比星脂质体用于治疗小鼠骨肉瘤的研究

目的 制备聚乳酸乙醇酸-聚乙二醇-聚乳酸乙醇酸共聚物(PLGA-PEG-PLGA)水凝胶包载的多柔比星(Doxorubicin,DOX)脂质体的复合载体,并考察其体外性质和抑瘤效果。方法 采用水化薄膜法制备DOX脂质体,考察其粒径分布和包封率,再利用PLGA-PEG-PLGA水凝胶包载制备得到的DOX脂质体得到DOX-Lip-Gel复合载体,考察其体外释放、黏性测试以及对荷瘤小鼠的治疗效果。结果 制备得到的DOX-Lip的粒径约为(89.3±4.7) nm,包封率约为(85.3±2.6)%,PLGA-PEG-PLGA水凝胶在25 ℃处于溶液状态,而在37 ℃时可凝固成胶,黏性测试结果表明水凝胶的相变温度约为30 ℃。并且水凝胶聚合物具有良好的生物相容性,在体内可以缓慢的降解。与对照组相比,DOX-Lip-Gel可以缓慢的释放药物,且释放期长达200 h。体内抑瘤实验表明DOX-Lip-Gel具有更好的抗肿瘤效果。结论 制备得到的DOX-Lip-Gel对荷瘤小鼠进行瘤周给药,对抑制骨肉瘤在小鼠体内的增长具有显著的抑制作用。     

Antiinflammatory, analgesic and free radical scavenging activities of the marine microalgae Chlorella stigmatophora and Phaeodactylum tricornutum

A pharmacological study of hydrosoluble and liposoluble extracts of the marine microalgae Chlorella stigmatophora and Phaeodactylum tricornutum indicated that hydrosoluble components of both species show significant antiinflammatory, analgesic and free radical scavenging activity. These activities were not detected in the liposoluble fractions.     

胰岛素柔性脂质体经小鼠皮肤给药的降血糖作用

 目的研究胰岛素柔性脂质体的制备及其对正常小鼠经皮给药的降血糖效果。方法以逆相蒸发-探针式超声法制备胰岛素柔性脂质体,对其形态、大小和包封率进行测定;以0.60U·cm^-2的剂量,将其非封闭性涂布于小鼠皮肤,用酶-苯酚法测定小鼠血糖,并与胰岛素普通脂质体、胰岛素溶液比较。结果胰岛素普通脂质体和柔性脂质体的粒径分别为(61.82±6.89),(74.O±7.65)nm,多分散性指数分别为(50.61±6.32)%,（14.62±4.01）%,包封率分别为(31.61±1.23)%,(35.35±3.49)%)n=3）。胰岛素柔性脂质体在1h内降糖百分率为(21.42±10.19)%,5h时达到（61.48士8.97）%,维持降糖时间18h。胰岛素普通脂质体和胰岛素溶液几乎没有降糖作用,与给予生理盐水对照组相当。结论柔性脂质体有较强的皮肤穿透作用,可能成为大分子药物经皮渗透的有效载体。     

参蛇洗剂的质量控制

目的建立参蛇洗剂的质量控制标准。方法采用薄层色谱定性鉴别参蛇洗剂中主药黄柏、蛇床子,采用高效液相法来测定苦参中的苦参碱。结果采用薄层色谱定性鉴别参蛇洗剂中主药黄柏、蛇床子,供试品色谱中,与对照品色谱相应的位置上显相同颜色的荧光斑点。采用高效液相法测定苦参中的苦参碱,苦参碱在0．53-4．77μg线性关系良好（r=r=0．9998）,平均回收率为98．5％。结论薄层色谱法定性鉴别蛇参洗剂主药黄柏、蛇床子,高效液相法来测定苦参中的苦参碱的含量,方法简单准确,重现性好,可用于参蛇洗剂的质量控制。     

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??OBJECTIVE To develop a polyethylene glycol (PEG) modified cationic liposomes for the co-delivery of siRNA and honokiol to improve tumor therapy. METHODS The PEG-modified cationic liposomes were prepared by thin film hydration method. Honokiol was loaded in the liposomes with hydrophobic interaction and siRNA was loaded with electrostatic interaction. The optimal formulation was screened according to size, Zeta potential, entrapment efficiency and serum stability. The liposomes were characterized with cellular uptake and intracellular localization of siRNA. The pharmacodynamic effect of honokiol-loaded liposomes (LH) and honokiol-siRNA-loaded liposomes (LH-siRNA) were verified by inhibition of cancer cell growth. RESULTS All the honokiol-loaded liposomes had an average particel size of about 100 nm with high drug entrapment efficiency. The optimal liposome formulation (N/P ratio of 5) exhibited the best cellular uptake. The results of pH-dependent hemolysis and intracellular localization suggested that the LH-siRNA had good ability of endosomal escape. In vitro cell growth experiments showed that both LH and LH-siRNA had good inhibition action on tumor cell growth based on the effects of honokiol and siRNA. CONCLUSION The PEG-modified cationic liposomes can be a potential carrier for co-delivery of siRNA and honokiol to tumors.     

硫酸铵梯度法制备莫西沙星脂质体的工艺研究

目的 制备具有较高包封率和载药量且体外放置稳定的莫西沙星脂质体。方法 采用硫酸铵梯度法制备包载莫西沙星的脂质体,以粒径及其分布和包封率、载药量为指标对处方和工艺进行优化。结果 最佳制备条件为：空白脂质体中硫酸铵质量浓度70 mg/mL、磷脂质量浓度50 mg/mL、脂质体粒径120 nm左右、透析时间5 h、载药时药脂比2∶3、孵育温度40 ℃、孵育时间30 min。制备得到的莫西沙星脂质体粒径为（143.00±3.98）nm,包封率为（74.56±3.21）%,载药量为（26.39±1.88）%。结论 硫酸铵梯度法制备的莫西沙星脂质体包封率较高,粒径均一,室温放置稳定性良好。     

乳糖化羧甲基壳聚糖包覆苦参碱脂质体在大鼠体内组织分布研究

 目的研究乳糖化羧甲基壳聚糖包覆的苦参碱脂质体的制备方法并考察其在大鼠体内的组织分布。方法采用逆相蒸发-短时超声法制备苦参碱脂质体。合成乳糖化羧甲基壳聚糖并用其包覆苦参碱脂质体。采用反相高效液相色谱法测定大鼠组织中的苦参碱浓度。结果包覆后脂质体的平均粒径无明显变化,Zeta电位由负转正,包封率为51.0%,渗漏率略有降低,包覆前后的脂质体的体外释放均符合Higuchi方程。乳糖化羧甲基壳聚糖包覆的苦参碱脂质体的肝脏AUC值相对于苦参碱脂质体和苦参碱溶液具有显著性差异(P<0.05),包覆后的苦参碱脂质体相对摄取率为肺脏>肝脏>脾脏。乳糖化羧甲基壳聚糖包覆的苦参碱脂质体、苦参碱脂质体和苦参碱溶液肝脏靶向效率分别为28.85%,20.93%和13.31%。结论与苦参碱溶液和普通脂质体相比,乳糖化羧甲基壳聚糖包覆的苦参碱脂质体可以提高肝靶向性。