淫羊藿苷壳聚糖/明胶微球的制备及其体外释放研究

本试验以壳聚糖、明胶为载药基质,以中药淫羊藿苷为模拟药物,通过乳化交联的方法制备淫羊藿苷/壳聚糖/明胶微球。考察微球的理化特性,建立持续流动释放系统,检测了微球的体外释放特性和影响因素。微球的理化特性受工艺条件如搅拌速度、乳化剂用量、交联剂用量等因素影响。微球的体外释放速率与微球的粒径、交联度负相关,与载药量正相关。试验结果表明,壳聚糖、明胶可作为缓释微球的载体基质,微球制备工艺简单稳定,微球的释放速率可控,淫羊藿苷/壳聚糖/明胶微球是一种良好的药物释放体系。     

阿司匹林-蒙脱土-壳聚糖缓释微球的制备及其体外释放性能

利用溶液法预先制备壳聚糖(Cs)-蒙脱土(MMT)复合材料(Cs-MMT),以Cs-MMT、Cs为原料,采用反相悬浮聚合法制得一种新型药物缓释体系阿司匹林-蒙脱土-壳聚糖载药微球(Asp-MMT-Cs)。采用FT-IR、SEM表征了Cs-MMT和Asp-MMT-Cs载药微球的结构及形态;设计正交实验优化了Asp-MMT-Cs载药微球的制备工艺;通过体外释放实验探讨了载药微球在不同模拟释放液中的释药规律。结果表明:所得微球球形度好,粒径分布较均匀;最优工艺制得的载药微球平均粒径为81.20μm,载药量为9.61%,包封率为76.78%。该缓释体系具有pH敏感性,更倾向于在pH较高的磷酸盐缓冲溶液中释放。     

聚(L-谷氨酸)微球的制备及其口服药物控释研究

通过正己胺引发γ-苯甲基-L-谷氨酸酯-N-内羧酸酐(BLG-NCA)开环聚合制备聚(γ-苯甲基-L-谷氨酸酯)(PBLG), 并进一步脱掉苯甲基保护得到聚(L-谷氨酸)(PLG). 以利福平为模型药物, 通过油包油(O/O)无水乳液法制备了PLG载药微球. 扫描电子显微镜检测表明该载药微球具有良好的球形形貌且粒径分布较均一, 粒径大小约为9.0 μm. 体外释放实验表明该载药微球对利福平的释放具有明显的pH敏感性, 在模拟胃液中较少释放利福平, 而在模拟肠液中较快并大量释放利福平, 符合口服药物载体释放性能的要求, 可用于口服药物的定位肠溶性载体. 此外, 噻唑蓝实验表明该微球具有良好的生物相容性.     

生物降解聚酯包埋利福平缓释微球的制备及释放行为

以生物可降解乙交酯和丙交酯的无规共聚物(PLGA)为载体,将抗结核病药利福平溶解于PLGA的有机溶液中,采用通常乳化-溶剂挥发方法制备了药物缓释微球.研究了影响微球制备的工艺条件.用电子显微镜观察了微球及降解后的表面形态,测定了微球粒径及载药量,评价了载药微球的体外释放行为.结果表明,以质量分数为1%的明胶为稳定剂,制备的微球形态完整,粒径范围为10～30μm,微球中利福平的平均质量分数为24.3%.体外释药时间可以通过高分子的降解速率来调控,本实验的释药时间可以在42～84d之间调控,药物缓释达到了理想的零级动力学释放.因此,利福平PLGA微球具有显著的长效、恒量药物缓释作用.     

粒径单分散克拉霉素缓释微球的制备研究

采用膜乳化法结合液中干燥法制备了克拉霉素乙基纤维素微球,当膜孔径为2.8及5.4μm、乙基纤维素浓度为5％～6％及投药量为1:2时,制得的克拉霉素乙基纤维素微球的载药量、包封率及收率均最高.考察了克拉霉素乙基纤维素微球的缓控释性能,结果表明:膜乳化法制得的克拉霉素乙基纤维素微球的缓控释效果明显优于溶剂挥发法,且膜孔径为...     

5-氟尿嘧啶/壳聚糖载药纳米微球的制备及性能

以三聚磷酸钠为交联剂,采用离子交联法制备了5-氟尿嘧啶/壳聚糖纳米微球,评价其性能、体外释药性能及对人肺癌细胞GLC-82的体外杀伤效应,并通过Zeta电位和红外光谱分析载药纳米微球形成机理.结果表明,所制备的5-Fu/CS纳米微球平均包封率为32.3%,平均载药量为25.6%,平均粒径为253nm,平均zeta电势为+8.38mV,成球性及分散性良好.CS载药纳米微球具有缓释性能,体外释药行为符合双向动力学规律.在体外作用72h,CS载药纳米微球对人肺癌细胞GLC-82的杀伤率达66.6%,杀伤效果明显优于5-Fu对照组.     

肾上腺髓质素微球复合PLGA/纳米羟基磷灰石支架材料的制备及生物活性评价

利用离子乳化交联法制备了负载肾上腺髓质素的壳聚糖微球,应用热致相分离法制备了乳酸和乙醇酸共聚物/纳米羟基磷灰石(PLGA/nHA)支架材料并在其中包覆载药微球.通过扫描电子显微镜、体外释放行为、材料溶血行为、碱性磷酸酶(ALP)活性的测定、支架材料表面细胞荧光染色和MTT[3-(4,5-二甲基噻唑-2)-2,5-二苯基四氮唑溴盐]比色法等手段综合评价载药支架材料的性能及生物活性.结果表明,微球直径均匀,载药支架孔径大小合适并相互穿通.支架材料的溶血率小于5%,符合医用材料的溶血实验要求.载药支架及支架材料本身对成骨细胞及血管内皮细胞的增殖以及成骨细胞的分化均有一定的促进作用.     

乳液静电纺丝PLA/PEG微纳纤维膜的可控制备及负载亲疏水性药物的释放

采用低能相反转法,以聚乳酸(PLA)、疏水性药物喜树碱(CPT)溶液为油(O)相,以明胶水溶液、亲水性药物黄芪多糖(APS)为水(W)相,制备水包油(O/W)初乳液.通过控制聚乙二醇(PEG)的浓度和分子量制备O/W纺丝液,经乳液静电纺丝获得PLA/PEG微纳纤维膜.采用粒径分布、光学显微镜(OM)、扫描电子显微镜(SEM)、红外光谱(FTIR)、X射线衍射(XRD)、接触角测试和细胞毒性实验对初乳液和PLA/PEG微纳纤维膜进行表征,并通过激光共聚焦显微镜(CLSM)观察药物的分布情况.结果表明,通过乳液静电纺丝可成功制备亲水性良好的不同微纳结构的PLA/PEG微纳纤维膜.PLA/PEG微纳纤维膜形貌不同,亲水性存在差异,无细胞毒性.体外药物释放结果表明,与pH=6.8和7.4的释放介质相比,在pH=5.8的释放介质中,药物累积释放率较高,表明载药PLA/PEG微纳纤维膜能够有效减缓CPT的释放,而APS释放速率较快,可实现亲疏水性药物的差别性释放.     

单分散聚苯乙烯微球的制备及表征

应用膜乳化-液中干燥法成功制备出粒径为2～20μm的单分散聚苯乙烯(PS)微球.PS微球的粒径主要由膜孔径决定,其值约为膜孔径的2倍;PS溶液的浓度对其也有一定的影响.膜乳化过程中的压力对微球粒径的分散性有很大的影响,在一定压力范围内,粒径呈单分散.在分散相中加入致孔剂,制备出表面多孔的PS微球.采用复乳-液中干燥法制备出中空PS微球.     

可降解聚合物包覆次血红素六肽微球的制备及生物活性

采用水包油包水(W₁/O/W₂)复乳溶剂挥发法制备了包覆次血红素六肽(DhHP-6)的2种聚酯微球. 通过扫描电子显微镜、 体外缓释行为、 高效液相(HPLC)检测、 酶活力测定和初步的动物实验等表征, 综合评价了载药微球的体外释放及体内生物活性. 实验结果表明, 载药微球球体圆整, 粒径分布均匀, 载药量高, 能够实现体外缓释, 并对细胞过氧化损伤和小鼠脑缺血损伤均有一定的保护作用.     

Preparation of insulin-loaded PLA/PLGA microcapsules by a novel membrane emulsification method and its release in vitro

Uniform-sized biodegradable PLA/PLGA microcapsules loading recombinant human insulin (rhI) were successfully prepared by combining a Shirasu Porous Glass (SPG) membrane emulsification technique and a double emulsion-evaporation method. An aqueous phase containing rhI was used as the inner water phase (w1), and PLA/PLGA and Arlacel 83 were dissolved in a mixture solvent of dichloromethane (DCM) and toluene, which was used as the oil phase (o). These two solutions were emulsified by a homogenizer to form a w1/o primary emulsion. The primary emulsion was permeated through the uniform pores of a SPG membrane into an outer water phase by the pressure of nitrogen gas to form the uniform w1/o/w2 droplets. The solid polymer microcapsules were obtained by simply evaporating solvent from droplets. Various factors of the preparation process influencing the drug encapsulation efficiency and the drug cumulative release were investigated systemically. The results indicated that the drug encapsulation efficiency and the cumulative release were affected by the PLA/PLGA ratio, NaCl concentration in outer water phase, the inner water phase volume, rhI-loading amount, pH-value in outer water phase and the size of microcapsules. By optimizing the preparation process, the drug encapsulation efficiency was high up to 91.82%. The unique advantage of preparing drug-loaded microcapsules by membrane emulsification technique is that the size of microcapsules can be controlled accurately, and thus the drug cumulative release profile can be adjusted just by changing the size of microcapsules. Moreover, much higher encapsulation efficiency can be obtained when compared with the conventional mechanical stirring method.     

Preparation of porous polylactide microspheres by emulsion‐solvent evaporation based on solution induced phase separation

Porous polylactide (PLA) microspheres were fabricated by an emulsion‐solvent evaporation method based on solution induced phase separation. Scanning electron microscopy (SEM) observations confirmed the porous structure of the microspheres with good connectivity. The pore size was in the range of decade micrometers. Besides large cavities as similarly existed on non‐porous microspheres, small pores were found on surfaces of the porous microspheres. The apparent density of the porous microspheres was much smaller than that of non‐porous microspheres. Fabrication conditions such as stirring rate, good solvent/non‐solvent ratio, PLA concentration and dispersant (polyvinyl alcohol, PVA) concentration had an important influence on both the particle size and size distribution and the pore size within the microspheres. A larger pore size was achieved at a slower stirring rate, lower good solvent/non‐solvent ratio or lower PLA concentration due to longer coalescence time. Copyright © 2005 John Wiley & Sons, Ltd.     

Formulation and Optimization of Alkaline Extracted Ispaghula Husk Microscopic Reservoirs of Isoniazid by Box-Behnken Statistical Design

The main objective of the present work was to formulate and optimize a microparticulate sustained release drug delivery system of isoniazid by using a novel, alkaline extracted ispaghula husk as a polymer. Isoniazid microspheres of alkaline extracted ispaghula husk were prepared by emulsification internal ionic gelation method. Results of preliminary trials indicated that the polymer concentration, cross-linking agent and stirring speed had a noticeable effect on size and surface morphology. A four-factor three-level Box-Behnken design was employed to study the effect of independent variables on dependent variables. The particle size and entrapment efficiency varied from 30.75 to 61.78 µm and 62.27% to 85.80% respectively, depending on the polymer concentration, concentration of cross-linker and stirring speed. Optimized microspheres batch based on point prediction tool of design software exhibited 83.43% drug entrapment and 51.53 µm particle size with 97.80% and 96.37% validity, respectively at the following conditions: sodium alginate (3.55% w/v), alkaline extracted ispaghula husk (3.60% w/v), cross-linker concentration (7.82% w/v), and stirring speed (1200 rpm). The optimized formulation showed controlled drug release for more than 12 hours. The drug release followed Higuchi kinetics via a non-Fickian diffusion.     

Regulation of cellular responses to macroporous inorganic films prepared by the inverse-opal method

Regenerative medicine for repairing damaged body tissues has recently become critically important. Cell culture scaffolds are required for the control of cell attachment, proliferation, and differentiation in in vitro cell cultures. A new strategy to control cell adhesion, morphology, and proliferation was developed by culturing mouse osteoblast-like MC3T3-E1 cells on novel cell culture scaffolds fabricated using ordered nanometer-sized pores (100, 300, 500, and 1000 nm). Results of this study indicate that after 72 h of incubation, the number of cells cultured on a silica film with a pore size of 1000 nm was similar to or slightly lower than that cultured on a non-porous control silica film. Films with 100-500 nm pore sizes, however, resulted in the cell growth inhibition. Morphology of the cultured cells revealed increased elongation and the formation of actin stress fibers was virtually absent on macroporous silica films with 100-500 nm pore size. Vinculin molecules expressed in cells cultured on the non-porous silica films showed many clear focal adhesions, whereas focal contacts were insufficiently formed in cells cultured on macroporous films. The influence of hydroxyapatite (HAp) and alumina scaffolds on the behavior of MC3T3-E1 cells was also evaluated. The proliferation rate of MC3T3-E1 cells cultured on HAp films with 1000 nm pore size was increased to approximately 20% above than that obtained of cells cultured on non-porous HAp films. These results demonstrate that the pore size and constituents of films play a role in controlling the morphology and proliferation rate of MC3T3-E1 cells.     

Aripiprazole Loaded Polymeric Biodegradable Microspheres: Formulation and In Vitro Characterization

In the present study, we attempted to prepare biodegradable microspheres of polylactic acid containing aripiprazole in order to achieve its controlled release profile suitable for parenteral administration. Biodegradable microspheres were prepared by solvent evaporation method using methylene dichloride as a solvent. The optimization of various formulation variables (e.g., stirring speed, and polymer:drug ratio, stabilizer concentration) to obtain spherical particles was also investigated. The optimized product was further characterized for various in vitro attributes, such as particle size and its distribution, encapsulation efficiency, surface properties, percentage yield, and in vitro release. Changing the ratio of polymer, stabilizers, and leaching agent (sodium chloride) affected the entrapment efficiency and release rate of aripiprazole. The release quantum was 88.41% when stirring rate was 2000 rpm and it was further increased to 94.65% when stirring speed was increased to 3000 rpm (Formulation E). Drug entrapment of microspheres was increased by increasing the concentration of PVP and maximum entrapment (62.35%) was obtained at 4% concentration of PVP (Formulation E). Spherical particles with good surface characteristics were obtained at stirring rate 3000 rpm and drug:polymer ratio 1:10.     

Microencapsulation of capsaicin by solvent evaporation method and thermal stability study of microcapsules

With polylactic acid (PLA) as shell and capsaicin as core substances, microcapsules were prepared based on solvent evaporation method. The orthogonal test was used to analyze the effects of the process conditions such as polyvinyl alcohol and PLA concentrations, stirring rate, and oil/water ratio on the particle size of the microencapsulated capsaicin (MC) agents. The chemical composition, morphology and size distribution of the microcapsules prepared by the most satisfactory conditions were analyzed by Fourier transform infrared spectroscopy, laser light scattering, and scanning electron microscopy. The MC agents had a mean diameter of 3–5 μm. The thermal properties of the MC agents were measured by differential scanning calorimetry and thermogravimetric analysis, it was demonstrated that the thermal stability of the MC agents was changed or even improved by the encapsulated PLA over the surface, when compared with similar parameters of the uncovered capsaicin. The in vitro release profile suggested that the microcapsules could be a suitable material for controlled release of capsaicin.     

Effect of polyethylene glycol on preparation of rifampicin-loaded PLGA microspheres with membrane emulsification technique

Monodisperse poly(lactide-co-glycolide) (PLGA) microspheres containing rifampicin (RFP), anti-tubercle drug, as hydrophobic model drug were prepared by solvent evaporation method with a membrane emulsification technique using Shirasu Porous Glass (SPG) membranes. Five kinds of rifampicin-loaded PLGA (RFP/PLGA) microspheres with different sizes were prepared by changing pore size of the membranes. Effect of polyethylene glycol (PEG) added to polyvinyl alcohol (PVA) solution (continuous phase) upon the monodispersity of microspheres was studied. PEG was used as a stabilizer for microspheres dispersing in PVA solution. The most suitable molecular weight of PEG as a stabilizer was 20,000. RFP/PLGA microspheres prepared with PEG20000 were apparently more uniform than those prepared without PEG. The yield of RFP/PLGA microspheres was 100%. The initial burst observed in the release of RFP from RFP/PLGA microspheres was suppressed by the addition of PEG.     

膜乳化-液中干燥法制备单分散高分子微球

粒径可控的单分散高分子微球,在分析化学中可用作高效液相色谱填料^[1,2];在化学工业中可用作催化剂载体;在生物领域中用于药物释放、癌症与肝炎等临床诊断、细胞标记与识别等^[3].高分子微球的制备方法大致可分为两类,一是利用由单体出发的聚合反应或缩聚反应形成微球,二是高分子溶液经物理或物理化学手段处理后形成微球^[4]