快速膜乳化法制备胸腺法新长效缓释微球

采用快速膜乳化技术结合溶剂蒸发法制备以生物可降解聚乳酸-羟基乙酸(PLGA)为载体的胸腺法新载药微球,考察了PLGA分子量、油相中PLGA和乳化剂浓度、外水相pH值和内水相体积等对微球包埋率和粒径的影响. 结果表明,制备粒径均一的PLGA载药微球的优化条件为：PLGA分子量51 kDa,油相中PLGA和乳化剂浓度为100和10 g/L,内水相体积0.5 mL,外水相pH值为3.5. 该条件下所制载药微球粒径均一性好(Span<0.7),药物包埋率高达80%以上,突释率24 h内低于20%,线性持续稳定释药时间长达30 d.     

三七皂苷R1-PLGA纳米微球的制备及优化研究

应用高分子有机化合物聚乳酸-羟基乙酸共聚物[Poly(lactide-co-glycolide),PLGA]作为成膜材料包载三七皂苷R1制备纳米微球并寻求最优制备条件。采用复乳-溶剂挥发法制备纳米微球,使用高效液相色谱仪、激光粒度分析仪,测定包封率及粒径。采用正交实验设计,对影响包封率及粒径的因素分别进行五因素四水平正交实验。在PLGA浓度10mg/m L,内水相∶油相体积比为3∶10,外水相与初乳体积比为10∶1,第一次超声乳化时间10s,第二次超声乳化时间90s的条件下制备的微球包封率最为理想。若要获得最小粒径,则优化实验条件为:PLGA浓度20mg/m L,内水相∶油相体积比为2∶5,外水相与初乳体积比为2∶1,第一次超声乳化时间10s,第二次超声乳化时间120s。以PLGA为外壳材料可制备携三七皂苷R1纳米微球,并能获得其包封率及粒径制备的最优化条件。     

奥曲肽长效生物可降解微球的制备工艺研究

运用复乳法制备奥曲肽PLGA长效生物可降解微球,并用正交法优化微球制备工艺。利用HPLC、显微镜、激光粒度仪等对微球进行综合质量研究。结果表明,复乳法制备奥曲肽微球的最佳工艺参数为:内水相药物与中油相PLGA的质量比为1∶5,中油相PLGA的浓度为10%,外水相乳化剂为1%的22 000分子量聚乙烯(PVA)水溶液,中油相与外水相的体积比不小于1∶50,复乳化采用机械搅拌法,搅拌速度为1 200 r/min。在该工艺条件下制得的微球,包封率为35.1%,载药量为2.98%,平均粒径为26.3μm,微球外观圆整,形态良好。     

树脂共混改性制备毒死蜱微胶囊

[目的]以聚甲基丙烯酸甲酯(PMMA)/聚碳酸亚丙酯(PPC)复合材料为壁材,制备毒死蜱微胶囊。[方法]以聚乙烯醇(PVA)-1788为连续相,采用乳化-溶剂挥发法制备微胶囊,利用激光粒度分析仪测定微胶囊粒径,通过光学显微镜对微胶囊形貌进行表征,高效液相色谱法(HPLC)测定微胶囊的包封率、载药量及缓释性能。[结果]经PMMA共混改性后的PPC载体微胶囊,平均粒径为7.15μm,经测载药量为27.56%,包封率为83.77%,对毒死蜱的缓释效应优于单纯以PPC为壁材的微胶囊,缓释期为33 d。[结论]2种聚合物共混改性后的微胶囊在降解性、缓释期上克服了以单一聚合物为壁材的缺点,载药量、包封率也较高。     

溶剂蒸发法制备辛酰溴苯腈微胶囊及其性能研究

为开发出辛酰溴苯腈新剂型,提高其防治效果,降低施用量,本研究以聚羟基丁酸酯(PHB)为壁材,辛酰溴苯腈为芯材,三氯甲烷为溶剂,聚乙烯醇(PVA)为乳化剂,采用溶剂蒸发法制备微胶囊,通过单因素及L₉(3⁴)正交设计试验确定其最佳制备工艺,测定其载药量、包封率、粒径及分布、缓释性能和除草活性。试验结果表明,辛酰溴苯腈微胶囊最佳制备工艺条件为芯壁材质量比为1∶5,油水体积比为1∶5,PVA质量分数为2%,剪切速率为12 000 r/min,其制备的微胶囊中位粒径D₅₀值为24.82μm,分散均匀,载药量为18.38%,包封率达91.90%。该微胶囊释放性能良好,148 h累积释放率达83%;辛酰溴苯腈微胶囊有效成分360 g/hm²药后7 d对藜的株防效为95.83%,与商用乳油制剂有效成分450 g/hm²的株防效无显著差异。制备的辛酰溴苯腈微胶囊能有效减少辛酰溴苯腈使用量。     

灭幼脲缓释微胶囊的制备与性能

[目的]通过对灭幼脲缓释微胶囊的制备和对其性能的测试来提高灭幼脲的稳定性与环境的相容性。[方法]采用壳聚糖和海藻酸钠作为囊壁材料,利用静电吸附层层自组装技术(Layer-by-Layer,LbL法)制备灭幼脲微胶囊。正交优化灭幼脲微胶囊制备工艺,利用扫描电子显微镜和激光共聚焦显微镜表征微胶囊表面结构,研究了微胶囊的体外释放行为。[结果]实验结果表明:分别加入1 mL海藻酸钠(1.0 g/L)、1 mL壳聚糖(1.0 g/L)、20 mg灭幼脲、1 mL氯化钙(1.0 g/L)能得到相对更好的结果。正交试验4个因素中,氯化钙质量浓度对评估结果影响最大;利用优化后的体系制备的灭幼脲微胶囊,平均粒径为10μm,Zeta电位为+23.5 mV;载药量和包封率分别为(68.8±0.86)%和(69.1±0.86)%。[结论]利用这种方法制备的灭幼脲微胶囊具备明显的缓释性能。     

5-FU-PLGA复乳微球的制备及体外释放

采用乳化溶剂挥发法制备W/O/W型5-FU-PLGA复乳微球,采用单因素设计考察了第一相体积比(内水相与油相)、第二相体积比(初乳与外水相)对复乳稳定性的影响,采用正交设计考察了搅拌温度、搅拌时间、辅料浓度和有机相中载体材料浓度对微球质量的影响,并对制备条件进行优化。最适宜制备条件为:第一相体积比为1:2,第二相体积比为1:1,搅拌温度为10 ℃、搅拌时间为6 h、辅料浓度为0.5%、有机相中载体材料浓度为15%。依据最适宜条件制备的微球圆整度良好、粒径范围窄,平均粒径5.20 μm,载药量为5.34%,包封率为77.22%。体外释放试验表明微球具有明显的缓释效果,释放行为符合Higuchi模型。     

复相乳化法制备聚乳酸/水杨酸钠微囊

以W/O/W复相乳化法,聚乳酸为壁材、水杨酸钠为芯材,制备聚乳酸/水杨酸钠微囊。聚乳酸/水杨酸钠微囊的工艺条件为:水杨酸钠溶液浓度为40 mg/mL,聚乳酸溶液浓度为25mg/mL,聚乙烯醇溶液浓度为2mg/mL,内水相水杨酸钠体积为2mL,油相聚乳酸溶液体积为10mL,外水相聚乙烯醇溶液体积为60mL,即内水相与油相比为1∶5,油相与外水相体积比为1∶6。聚乳酸/水杨酸钠微囊的包封率为75.70%。     

O-季铵化-N-(4-十二烷氧基)壳聚糖苯甲醛席夫碱的制备及胶束pH响应性

制备双亲性的O-季铵化-N-(4-十二烷氧基)壳聚糖苯甲醛席夫碱(QA-CS-DBA),采用FTIR、¹H NMR及元素分析对产物进行表征。通过超声法制备QA-CS-DBA载酮洛芬胶束,考察胶束的临界胶束浓度、粒径、Zeta电位、载药量和包封率,并对胶束在不同pH值条件下的药物释放行为及Zeta电位变化进行研究。结果表明,QA-CS-DBA能将酮洛芬包载于胶束疏水内核,载药量为39.37%,包封率为46.04%,载药胶束粒径为341nm,Zeta电位为30.8mV。胶束Zeta电位及载药胶束的药物释放行为具有pH响应性。     

壳聚糖-阿拉伯胶/雷公藤微胶囊的制备

以壳聚糖、阿拉伯胶为壁材,雷公藤提取物为芯材,采用复凝聚法制备壳聚糖-阿拉伯胶/雷公藤微胶囊。以雷公藤提取物含量、芯材比、反应温度、搅拌转速为考察因素,以载药量、包封率为评价指标,通过正交实验对制备工艺进行优化,并测定了微胶囊的药物释放性能。结果表明,微胶囊的最佳制备工艺为:雷公藤提取物含量15%、芯材比1∶1(g∶g)、反应温度45℃、搅拌转速500r·min~(-1),在此条件下,载药量与包封率分别达到86.22%和54.75%,所得微胶囊呈球形,未发生粘连现象,其在人工肠液中的药物释放性能稳定性高,50min左右即可释放出雷公藤有效成分。     

微流芯片制备粒径均一的壳聚糖-NaCS/TPP微胶囊

以壳聚糖、纤维素硫酸钠（NaCS）和三聚磷酸钠（TPP）为原料,采用十字型微流芯片制备了粒径均一的壳聚糖-NaCS/TPP微胶囊,微通道宽200 μm,高1 mm。分析了微通道内的三种流动状态、分散剂用量、壳聚糖浓度、油水两相流速等因素对壳聚糖微液滴形成的影响,确定了合适的制备条件。以2%(质量)壳聚糖醋酸水溶液为水相,液体石蜡为油相,5%(质量)Span 85为油相分散剂,水相流速5 μl·min^-1,调节油相/水相流速比为40～100,可以形成均匀的壳聚糖微液滴,粒径分布系数小于0.1。壳聚糖微液滴与1% NaCS和3% TPP的混合溶液反应,固化形成了中间空心、周边由两层膜构成的壳聚糖-NaCS/TPP微胶囊。结果表明,采用微流芯片可以有效控制液滴直径,制备粒径均一的微胶囊。     

阿司匹林壳聚糖-明胶载药微胶囊的制备及性能研究

以阿司匹林为囊芯,壳聚糖和明胶为壁材,采用乳化交联法制备了明胶-壳聚糖微胶囊,考察了芯壁比、水油体积比、乳化剂用量、交联时间等因素对微胶囊性能的影响.采用高效液相色谱法来测定微胶囊的载药量、包封率和释放性能.研究发现,当芯壁比为1∶1,水油体积比为1∶3,乳化剂Span-80用量为5％,交联时间为2h的条件下制备的微胶囊形状规整,载药量为47.99％,包封率为83.18％,且在人工肠液中具有明显的缓释效果.     

叶面亲和型阿维菌素微胶囊的制备及pH响应性释放性能

为减少农药流失,设计了一种叶面亲和型缓释微胶囊。以甲基丙烯酸甲酯（MMA）接枝改性羧甲基纤维素（CMC）得到羧甲基纤维素-聚甲基丙烯酸甲酯（CMC-g-PMMA）,然后利用自组装负载阿维菌素（AVM）形成载药微胶囊（CMC-g-PMMA@AVM）,通过多巴胺（DA）包覆提高CMC-g-PMMA@AVM的叶面亲和性。采用扫描电镜、红外光谱、热重分析等对其结构和形貌进行表征,研究了微胶囊的载药性能、叶面亲和性及响应释放性能。结果显示,DA/CMC-g-PMMA@AVM为平均粒径126nm的球形粒子,多巴胺的包覆可有效提高微胶囊的载药性能,包封率可达88.56%;增强AVM的叶面亲和性,使其叶面滞留量相对于阿维菌素水乳液提升30.56%;赋予AVM优异的抗紫外光分解性能,强紫外光照射60min后,由AVM水乳液中AVM的残留率14.03%提高到DA/CMC-g-PMMA@AVM中的59.55%。载药微胶囊中药物释放具有pH响应,在pH=5条件下出现爆释,药物释放过程符合Weibull模型,受Fick扩散控制。     

Preparation of carbon dioxide/propylene oxide/ε-caprolactone copolymers and their drug release behaviors

Summary Poly (propylene-ram-ε-caprolactone carbonate) (PPCL) and poly (propylene carbonate) (PPC) were synthesized by ring-opening copolymerization from carbon dioxide, propylene oxide (PO) and ε-caprolactone (CL) using a polymer-supported bimetallic complexes (PBM) as catalyst. PPC and PPCL microspheres containing a 5-alpha reductase inhibitor, finasteride were elaborated by a conventional oil-in-water (O/W) emulsion-solvent evaporation method. The effects of polymer used on microspheres morphology, size, drug loading, encapsulation efficiency and drug release behaviors were examined. In vitro drug release of these microcapsules was performed in a pH 7.4 phosphate-buffered solution. A prolonged in vitro drug release profile was observed. The release profiles of finasteride from PPC and PPCL microcapsules were found to occur with a burst release followed by a gradual release phase. Drug release rates were dependent upon the properties of the polymer in the microspheres, the higher hydrolytic activity of polymer provided faster release rate.     

纤维素硫酸钠的批量制备及其NaCS-PDMDAAC微胶囊固定化黄色短杆菌培养过程研究

在非均相反应制备纤维素硫酸钠方法的基础上,通过增加液固比,引入搅拌,使体系的温度分布和浓度分布都得到很大改进,由此可以保证产品质量的均一性。用正交试验进行了500 mL反应器制备条件的摸索,并将其逐步放大到1 L、5 L反应器中进行,确立了5 L规模的生产工艺条件。通过对不同规模下制得的硫酸纤维素钠产品在理化性质、制备微胶囊及在微囊化培养等方面对比较,表明研制过程有利于合成出高质量的硫酸纤维素钠,用于制备微胶囊。用NaCS-PDMDAAC(聚二甲基二烯丙基氯化铵—硫酸纤维素钠)微胶囊固定化黄色短杆菌,考察了葡萄糖浓度、摇床转速对黄色短杆菌生长和代谢谷氨酸的影响,确定了一个较优培养条件。胶囊平均生产能力达15.29 g /(Lh)(对微胶囊)。微胶囊固定化黄色短杆菌连续培养12批后,仍具有良好的代谢谷氨酸性能。     

重组人粒细胞-巨噬细胞集落刺激因子壳聚糖-海藻酸钠微囊的制备

目的以壳聚糖和海藻酸钠为原料,制备重组人粒细胞-巨噬细胞集落刺激因子(rhGM-CSF)微囊,探讨开发口服蛋白多肽类药物的可行性。方法以rhGM-CSF为药物模型,通过壳聚糖与海藻酸钠聚电解质的络合反应制备rhGM-CSF壳聚糖-海藻酸钠微囊,观察微囊的形态大小,测定其包封率,不同pH值下的膨胀度和体外释放率。结果制备的rhGM-CSF壳聚糖-海藻酸钠微囊呈均匀、完整的圆球形,平均直径1mm左右;包封率达80%以上;在模拟肠液(磷酸盐缓冲液,pH7.4)中浸泡3h,膨胀度可达600%,药物释放率达85%以上。结论壳聚糖-海藻酸钠微囊具有肠溶控释作用,有望成为rhGM-CSF等蛋白类口服药物的控释载体。     

Preparation of microcapsules of W/O/W emulsions containing a polysaccharide in the outer aqueous phase by spray‐drying

A water‐in‐oil‐in‐water (W/O/W) multiple emulsion containing a hydrophilic substance, 1,3,6,8‐pyrenetetrasulfonic acid tetrasodium salt (PTSA), and a wall material in its inner and outer aqueous phases, respectively, was prepared by a two‐step emulsification using a rotor/stator homogenizer, and was further homogenized with a high‐pressure homogenizer. Maltodextrin or gum arabic were used as wall materials, and olive oil was used as the oily phase. The high encapsulation efficiency for PTSA (>0.9) was realized. The emulsion was spray‐dried to produce microcapsules of W/O/W type. The efficiencies of the microcapsules prepared with maltodextrin and gum arabic were 0.82 and 0.67, respectively. Stability of the microcapsules was examined at 37 °C and 12%, 33% and 75% relative humidity. Microcapsules prepared with maltodextrin were more stable than those prepared with gum arabic.     

Preparation and properties of poly(propylene carbonate maleate) microcapsules for controlled release of pazufloxacin mesilate

A novel biodegradable aliphatic polycarbonate, poly(propylene carbonate maleate) (PPCMA) was synthesized by terpolymerization of carbon dioxide, propylene oxide, and maleic anhydride (MA), using a polymer supported bimetallic complex as catalyst. The utility of PPCMA to encapsulate and control the release of drug pazufloxacin mesilate (PZFX), via microcapsules, was investigated. PPCMA microcapsules containing PZFX were elaborated by solvent evaporation method based on the formation of double W/O/W emulsion. The manufacturing parameters such as the volume ratio of V(PPCMA) : V(PZFX), the concentration of stabilizer gelatin in outer aqueous phase played major roles on microcapsule characters, and were altered to optimize the process parameters. The PPCMA‐PZFX microcapsules were obtained with smooth and spherical surface under optimum condition, the mean diameter of microcapsules was ～ 2 μm, and the drug loading and drug encapsulation efficiency of the microcapsules were 22.9 ± 1.05% and 82.1 ± 2.03%, respectively. PZFX released from PPCMA microcapsules was found to reach 89.8 ± 2.89% after 36d in a pH 7.4 phosphate‐buffered solution, and the release profile obeyed the Higuchi equation. The results suggest that the new polymer PPCMA provides an alternative to degradable matrix polymers for long‐term sustained releasing drug delivery systems. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011     

Poly(L‐histidine)‐chitosan/alginate complex microcapsule as a novel drug delivery agent

Novel poly(L ‐histidine)‐chitosan/alginate complex microcapsules were prepared from biodegradable polymers poly(L ‐histidine) (PLHis) in the presence of chitosan at acetate buffer solution pH 4.6. Microcapsules obtained are spherical and well‐dispersed with a smooth surface and a narrow size distribution. The microcapsules can encapsulate the protein model drug hemoglobin (Hb) efficiently. The results show that the complex microcapsules with low, medium, or high molecular weight of chitosan (0.05%, w/v), the highest encapsulation efficiencies obtained are 91.3%, 85.9%, and 94.2% with loading efficiencies of 47.8%, 44.3%, and 39.7%, respectively. The release profiles indicate that Hb‐loaded microcapsules conform to first‐order release kinetic in whole procedure, and 84.8%, 71.4%, and 87.3% of Hb were released during 72‐h incubation in PBS pH6.8 for microcapsules with low, medium, and high molecular weight chitosan (0.05%, w/v), respectively. The results also indicate that particle size and drug loading efficiency have a significant influence on the release profile and encapsulation efficiency. Our results reveal that the PLHis‐chitosan/alginate complex microcapsules are able to encapsulate and release Hb and are potential carriers for protein drugs. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2012