海藻酸微胶囊的制备及在药物控释中的研究进展

海藻酸具有相对温和的凝胶条件与良好的生物相容性 ,已广泛应用于药物缓释与生物医学工程。综述了海藻酸微胶囊的制作方法、增加海藻酸微囊的稳定性与控制物质扩散的主要方法及海藻酸凝胶在药物控释研究中的进展     

再生丝素蛋白/海藻酸盐包药微胶囊的结构与释药性能

以模型药物消炎痛(吲哚美辛)作囊芯,再生丝素蛋白和海藻酸盐(FB/AG)作囊膜,在液体石蜡,Span-80的W/O型乳化体系中于50～60℃,高速搅拌下,采用复凝聚法制备包药微胶囊。采用扫描电镜(SEM)、激光粒度仪、X ray、FTIR、DSC等测定并表征了包药微胶囊的结构。结果显示,微胶囊呈近似球型,粒径为65μm左右,粒径呈正态分布,再生丝素蛋白与海藻酸盐之间具有相互作用,结晶程度提高。采用药物体外释放法测其释药性能,该包药微胶囊24h的释药率为24%,海藻酸盐微胶囊为42%,药粉为80%,FB/AG具有缓释效果。     

药物控释体系的研究与控释技术进展

介绍了药物控释体系的种类、作用机理及控释技术最近进展 ,指出发展控释技术意义重大     

海藻酸盐/壳聚糖复合微球的制备及其控制释放作用

采用喷雾干燥法将活性成分包载到海藻酸钠微凝胶中,再经钙离子和壳聚糖交联得到复合微球。以维生素B₂为模型药物探讨了微球的控制释放效果和机理。扫描电镜分析表明海藻酸钠微凝胶经复合交联后形成了团聚体结构。与单一钙离子交联的海藻酸盐微球相比,复合微球对维生素B₂释放更慢,半数释放时间(t₅₀)延长约6倍,且交联时间越长、交联剂用量越高,维生素B₂释放越慢。当载药量介于16.0%～35.6%时,维生素B₂释放时间达24 h以上,释放过程主要受费克扩散控制。     

氟碳化合物FC-77在Pluronic嵌段共聚物胶束中包封与缓释

采用乙醇注入法制备FC-77的载药纳米胶束,通过动态光散射、透射电子显微镜表征了载药纳米胶束的粒径和形貌;通过紫外可见光谱研究了FC-77在嵌段共聚物P123中的包封率和释放曲线。结果表明,含1%P123的FC-77载药纳米胶束粒径为270 nm,呈球形分布,包封率为50%6,00 min时的释放量为92.2%。进一步地,通过调节嵌段共聚物的组成、浓度等可以改变载药纳米胶束的粒径和包封率。结果证明,嵌段共聚物胶束体系能作为FC-77载药制剂的载体,并且通过调整嵌段共聚物胶束体系配方,可以得到理想的FC-77药物载体。     

A Dissolution‐Diffusion Model and Quantitative Analysis of Drug Controlled Release from Biodegradable Polymer Microspheres

Controlled release behaviours of nifedipine loaded poly (D,L‐lactide) (PLA) and poly(D,L‐lactide‐co‐glycolide) (PLGA) microspheres are investigated and modelled in this paper. Based on the integrated consideration of diffusion, finite dissolution rate, moving front of dissolution and size distribution of microspheres, a mathematic model is presented to quantitatively describe the drug release kinetics. The coupled partial differential equations are numerically solved. Dynamic concentration profiles of both dissolved and undissolved drug in the microspheres are analyzed. In comparison with the diffusion model and Higuchi model, the proposed dissolution‐diffusion model is characteristic of describing the whole release process without limitation of different dissolution rate or dissolubility. The diffusion coefficient and the dissolution rate constants are evaluated from measured release profiles. The effects of microstructures of polymer microspheres on release behaviours are related to parameters of the model. Based on the mathematical model and in vitro release data, intrinsic mass transfer mechanism is further investigated.     

药物与聚乳酸包埋物缓释性能的研究

采用包埋法制备了聚乳酸与药物的混合物,测定了聚乳酸相对分子质量大小、聚乳酸与药物的配比、聚乳酸与不同药物形成的包埋物及光照对药物释放量的影响,研究了包埋物在不同环境下的释放能力。     

Improved Controlled Release and Brain Penetration of the Small Molecule S14 Using PLGA Nanoparticles

Phosphodiesterase 7 (PDE7) is an enzyme responsible for the degradation of cyclic adenosine monophosphate (cAMP), an important cellular messenger. PDE7’s role in neurotransmission, expression profile in the brain and the druggability of other phosphodiesterases have motivated the search for potent inhibitors to treat neurodegenerative and inflammatory diseases. Different heterocyclic compounds have been described over the years; among them, phenyl-2-thioxo-(1H)-quinazolin-4-one, called S14, has shown very promising results in different in vitro and in vivo studies. Recently, polymeric nanoparticles have been used as new formulations to target specific organs and produce controlled release of certain drugs. In this work, we describe poly(lactic-co-glycolic acid) (PLGA)-based polymeric nanoparticles loaded with S14. Their preparation, optimization, characterization and in vivo drug release profile are here presented as an effort to improve pharmacokinetic properties of this interesting PDE7 inhibitor.     

温度及pH敏感的水凝胶微球合成及其药物缓释研究

采用乳液聚合法,以N-异丙基丙烯酰胺(NIPAM)和丙烯酸(AAc)为功能单体,共聚制备了粒径较为均匀的水凝胶微球.该微球具有温度及pH双重敏感性,其最低临界溶解温度(LCST)随着pH值及AAc含量的不同而改变.此外,还以吡啶硫酮钠(ZNP)为水溶性小分子药物模型,研究了该微球对该药物的负载及控释情况.研究显示,吡啶...     

Drug Release Kinetics and Mechanism from PLGA Formulations

The release kinetics of indomethacin (IND) and hydrochlorothiazide (HCT) from drug/PLGA formulations with different copolymer composition and molecular weight of PLGA were measured in vitro by using a rotating disk system (USP II). The release mechanism of IND and HCT from their PLGA formulations was analyzed using a chemical‐potential‐gradient model combined with the Perturbed‐Chain Statistical Associating Fluid Theory (PC‐SAFT). Furthermore, the release kinetics of IND and HCT from the PLGA formulations with different copolymer composition and molecular weight of PLGA were correlated and predicted in good accordance with the experimental data. It was found that the chemical‐potential‐gradient model combined with the PC‐SAFT helped to understand the drug release mechanism from the drug/PLGA formulations. It also well correlated and predicted the drug release kinetics as function of copolymer composition and molecular weight of PLGA as well as of drug type. It helps to save time and costs for determination of the long‐term drug release kinetics, especially for sustained drug release as obtained from the drug/PLGA formulations in this work. © 2016 American Institute of Chemical Engineers AIChE J, 62: 4055–4065, 2016     

PLGA Biodegradable Nanoparticles Containing Perphenazine or Chlorpromazine Hydrochloride: Effect of Formulation and Release

In our study, poly(dl-lactide-co-glycolide) (PLGA) nanoparticles loaded with perphenazine (PPH) and chlorpromazine hydrochloride (CPZ-HCl) were formulated by emulsion solvent evaporation technique. The effect of various processing variables, including PLGA concentration, theoretical drug loading, poly(vinyl alcohol) (PVA) concentration and the power of sonication were assessed systematically to obtain higher encapsulation efficiency and to minimize the nanoparticles size. By the optimization formulation process, the nanoparticles were obtained in submicron size from 325.5 ± 32.4 to 374.3 ± 10.1 nm for nanoparticles loaded with PPH and CPZ-HCl, respectively. Nanoparticles observed by scanning electron microscopy (SEM) presented smooth surface and spherical shape. The encapsulation efficiency of nanoparticles loaded with PPH and CPZ-HCl were 83.9% and 71.0%, respectively. The drug loading were 51.1% and 39.4% for PPH and CPZ-HCl, respectively. Lyophilized nanoparticles with different PLGA concentration 0.8%, 1.3% and 1.6% (w/v) in formulation process were evaluated for in vitro release in phosphate buffered saline (pH = 7.4) by using dialysis bags. The release profile for both drugs have shown that the rate of PPH and CPZ-HCl release were dependent on a size and amount of drugs in the nanoparticles.     

Novel Chitosan-Silica Hybrid Hydrogels for Cell Encapsulation and Drug Delivery

Hydrogels constructed from naturally derived polymers provide an aqueous environment that encourages cell growth, however, mechanical properties are poor and degradation can be difficult to predict. Whilst, synthetic hydrogels exhibit some improved mechanical properties, these materials lack biochemical cues for cells growing and have limited biodegradation. To produce hydrogels that support 3D cell cultures to form tissue mimics, materials must exhibit appropriate biological and mechanical properties. In this study, novel organic-inorganic hybrid hydrogels based on chitosan and silica were prepared using the sol-gel technique. The chemical, physical and biological properties of the hydrogels were assessed. Statistical analysis was performed using One-Way ANOVAs and independent-sample t-tests. Fourier transform infrared spectroscopy showed characteristic absorption bands including amide II, Si-O and Si-O-Si confirming formation of hybrid networks. Oscillatory rheometry was used to characterise the sol to gel transition and viscoelastic behaviour of hydrogels. Furthermore, in vitro degradation revealed both chitosan and silica were released over 21 days. The hydrogels exhibited high loading efficiency as total protein loading was released in a week. There were significant differences between TC₂G and C₂G at all-time points (p < 0.05). The viability of osteoblasts seeded on, and encapsulated within, the hydrogels was >70% over 168 h culture and antimicrobial activity was demonstrated against Pseudomonas aeruginosa and Enterococcus faecalis. The hydrogels developed here offer alternatives for biopolymer hydrogels for biomedical use, including for application in drug/cell delivery and for bone tissue engineering.     

难溶性固体农药微胶囊化及控制释放研究进展

难溶性固体化合物广泛存在于农药、医药等领域,其稳定性受多种环境因素影响,在应用上存在微胶囊化的需要。介绍了难溶性农药微胶囊化适用的制备方法、芯材释放速率的调控方法和影响因素的研究进展。     

复相乳化法制备聚乳酸微胶囊及其性能考察

采用W/O/W复乳-溶剂蒸发法制备聚乳酸微球得到的最优制备条件:油水相比例5︰2、卡培他滨浓度为1.0mg/mL、外水相药液浓度5.0mg/mL,外水相体积20mL,几丁聚糖浓度为0.50%。以抗癌药卡培他滨为模型,考察了几丁聚糖浓度对聚乳酸微胶囊缓释性能的影响。结果表明:随着几丁聚糖浓度的增加,微囊释放速率相应降低。     

An Enhanced Water Solubility and Stability of Anthocyanins in Mulberry Processed with Hot Melt Extrusion

Mulberry fruits are rich sources of anthocyanins that exhibit beneficial biological activity. These anthocyanins become instable in an aqueous media, leading to their low bioavailability. In this study, a colloidal dispersion was produced by processing mulberry samples with hot-melt extrusion. In this process, hydrophilic polymer matrices were used to disperse the compound in an aqueous media. Mulberry samples were processed with hot-melt extrusion and in the presence of an ionization agent and sodium alginate to form mulberry-extrudate solid formulations. The particle size of mulberry-extrudate solid formulations decreased, while the total phenol content, the total anthocyanin content, and solubility increased. Fourier transform infrared spectroscopy (FT-IR) revealed that mulberry-extrudate solid formulations now contained new functional groups, such as –COOH group. We investigated whether mulberry-extrudate solid formulations had a positive impact on the stability of anthocyanins. The non-extrudate mulberry sample and mulberry-extrudate solid formulations were incubated with a simulated gastric fluid system and an intestinal fluid system. The number of released anthocyanins was determined with HPLC. We found that anthocyanins were released rapidly from non-extrudate mulberry extract. Mulberry-extrudate solid formulations contained a large number of available anthocyanins even after being incubated for 180 min in the intestinal fluid system. Thus, hot-melt extrusion enhanced water solubility and stability of anthocyanins with the prolonged release.     

Temperature-Sensitive Microspheres for Controlled Release of Enalprilmaleate

Poly(N′-isopropylacrylamide-co–methacryl amide) has been prepared by free-radical emulsion polymerization. The copolymer was transformed into thermoresponsive microspheres by chemical crosslinking with N′, N′ Methylenebis-acrylamide (NNMBA). Enalpril maleate (ENAM), an anti-hypertensive drug, was successfully loaded into these microspheres during in-situ polymerization. DSC and X-RD analysis of the drug-loaded and plain microspheres have confirmed partial dispersion of ENAM in the microspheres. SEM confirmed the spherical nature of the particles with a mean particle size of 100 µm. Drug release profiles of these microspheres exhibited a prolonged release of ENAM for more than 12 h.     

单分散性PLGA磁性微球的制备及其缓释性

为获得单分散性PLGA磁性微球,以纳米四氧化三铁明胶分散液作为内水相(W1),PLGA(聚乳酸羟基乙酸共聚物)的二氯甲烷溶液作为油相(O),PVA(聚乙烯醇)水溶液作为外水相(W2),利用T型微通道并采用复合乳液法制备PLGA磁性微球,考察油相(O)质量浓度、外水相(W2)质量分数、流速比及油相与内水相体积比对微球制备的影响。借助FTIR、SEM、光学显微镜及VSM(振动样品磁强计)对磁性微球组分、形貌、粒径分布和磁学性能进行表征;并以阿司匹林作为药物模型进行缓释性测试。结果表明:油相中PLGA质量浓度为0.050kg/L,外水相(W2)中PVA质量分数为1%及2%,流速比v(W2)∶v(W1/O)=120∶1且体积比V(O)∶V(W1)=2∶1时可均匀成球,其粒径分布系数CV值仅为4.66%,表现出良好的单分散性;此时,比饱和磁化强度可达1.52emu/g,兼具优异顺磁性。制得的载药微球在60 h内表现出阶段性匀速释放,且有较好的磁响应性,有望用于磁响应性药物载体。     

可生物降解药物控释系统的研究进展

可生物降解药物控释系统具有智能化、效率高和使用方便等特点,在药物控制释放研究领域越来越受到瞩目.基于国内外大量研究文献,对可生物降解药物控释系统进行了综述,着重介绍了温度和pH敏感型可生物降解智能化高分子给药系统的研究进展.     

二硫键交联的巯基化壳聚糖水凝胶对蛋白质还原响应的控制释放

以壳聚糖(CS)、N-乙酰-L-半胱氨酸(NAC)为原料,合成了巯基化壳聚糖(CS-NAC),并于CS-NAC的磷酸盐缓冲溶液(PBS)中通过氧化交联巯基形成二硫键制备了CS-NAC水凝胶。Ellman法测定结果表明:该水凝胶巯基质量摩尔浓度为275.8μmol/g。采用~1HNMR和FTIR表征了CS-NAC的结构并采用SEM及UV-vis对CSNAC进行了性能测试。结果表明:当w(CS-NAC)=1.5%~3.0%时可以形成稳定的凝胶结构,当CS-NAC质量分数从1.5%增加至3.0%时,水凝胶溶胀比从45.5降低至31.2,网孔尺寸从340 nm减小至242 nm。该二硫键交联的水凝胶可发生还原响应的降解,CS-NAC水凝胶在含10 mmol/L二硫苏糖醇(DTT)的PBS溶液中400 min内质量降解80%,在含50 mmol/L L-半胱氨酸(L-Cys)的PBS溶液中180 min可被完全降解。原位装载牛血清蛋白(BSA)的CS-NAC水凝胶可实现对BSA还原响应的控制释放,在含10 mmol/L DTT的PBS溶液中BSA累积释放量可高达80%,表现出典型的Fickian扩散控制释放行为。     

新型负载5-氨基水杨酸微胶囊的制备及其载药效果

采用锐孔/聚合法制备了平均粒径为1.89 mm、负载5-氨基水杨酸(5-ASA)的纤维素硫酸钠(NaCS)-壳聚糖微胶囊,采用Box-Behnken响应面法进行实验设计和分析,考察了内、外水相pH值和NaCS浓度、多聚磷酸钠(PPS)浓度对微胶囊载药量和包封率的影响. 结果表明,内水相pH值对负载5-ASA微胶囊的载药量和包封率起关键作用. 最佳制备条件为内水相pH 4.25,外水相pH 6.0,NaCS浓度14 g/L, PPS浓度5 g/L,该条件下所制微胶囊最大载药量为59.02%,最大包封率为89.96%..