pH-Sensitive performance of dextran–poly(acrylic acid) copolymer and its application in controlled in vitro release of ibuprofen

Dextran–poly(acrylic acid) copolymers (D-A) are prepared through copolymerizing of acrylic acid (AA) with dextran. Their structural properties and performances are characterized using various methods. The results indicate that the carboxyl groups of poly(acrylic acid) strongly interact with the proton acceptors of glucose units in dextran, and the effects of AA/dextran molar ratio on the pH sensitivity of obtained copolymers are remarkable. The D-A copolymer shows a smart pH response, specifically, shrinkage in a low pH medium and swelling at high pH. The potential application of D-A copolymer as a drug delivery matrix is explored using ibuprofen as a model drug.     

介孔水化硅酸钙微球的形貌控制及载药性能研究

以氢氧化钙和正硅酸四乙酯为原料,采用共沉淀法制备出了一系列的水化硅酸钙(CSH),通过X射线衍射(XRD)、扫描电子显微镜(SEM)等探讨了不同的酒精添加量和有机溶剂添加对CSH的物相和形貌的影响。结果表明;随着酒精添加量的增加CSH的分散性逐渐变好,采用丙三醇作为有机溶剂可以得到分散较好CSH微球。对CSH进行了布洛芬(IBU)载药研究,利用热重-差热分析、Brunauer-Emmett-Teller法和红外光谱表征(FT-IR)合对其在不同载药时间的CSH载药量、比表面积、孔容和表面基团等进行了分析。发现在12 h后载药量达到116.78%,有望成为较好的药物载体材料。     

Controlled drug release carriers based on PCL/PEO/PCL block copolymers

In order to create a new drug delivery system, the ibuprofen-loaded triblock copolymer PCL/PEO/PCL (PCEC) microspheres with a low PEO content (<2?wt%) were prepared by oil in water (o/w) solvent evaporation technique. The influence of PEO content, molecular weight of a polymer matrix and drug loading on the ibuprofen release profiles were evaluated. The interactions between polymer matrix and ibuprofen were detected by FTIR analysis. The presence of hydrophilic PEO segment in PCL chains caused the decrease in particle size, which further had a great impact on the drug release kinetics, i.e., initially faster release and significantly higher quantity of released drug compared to neat PCL. Ibuprofen release behavior from polymer matrix was governed by a diffusion process. In vitro cytotoxicity tests revealed that empty PCL and PCEC microspheres were not toxic at low concentrations, while ibuprofen-loaded microspheres exhibited cytotoxicity correlated with amounts of incorporated drug.     

明胶微球载药及其体外释放性能研究

以阿司匹林为药物模型分子,制备了载阿司匹林明胶微球。SEM研究表明,明胶微球在载药后,表面结构变得更为紧实。载药性能探讨表明,当阿司匹林的投药量为16mg时,明胶微球的载药性能较优（载药量为7．3％,包封率为57．5％）。对明胶微球在人工体液中的释药性能研究显示,载阿司匹林明胶微球具有良好的缓释性能。由于具有较大的酸性和胃蛋白酶的存在,微球在人工胃液中药物释放效率较高,在人工胃液和人工肠液中药物的释放率分别为40％和28％,且一级动力学模型对微球的体外药物释放情况拟合度较高。     

PVA-SA复合微球的制备及性能研究

用溶液共混法制备聚乙烯醇-海藻酸钠(PVA-SA)复合微球,考察了SA质量分数、PVA质量分数、CaCl2质量分数、m(PVA)/m(SA)和干燥方式对PVA-SA复合微球制备的影响,并测定了微球的含水率、溶胀率、载药量和包封率,通过红外光谱(FTIR)对微球进行了表征,研究了不同m(PVA)/m(SA)的PVA-SA复合微球对药物的缓释作用。结果表明,SA质量分数为6%,PVA质量分数为10%,CaCl2质量分数为5%,m(PVA)/m(SA)为1∶3时,可以制备出各项性能较好的微球,其载药率30.24%,包封率90.11%,并且有良好的缓释效果。     

静电喷雾法制备聚乳酸/布洛芬微球及其性能研究

采用静电喷雾技术,以聚乳酸（PLA）为骨架载体材料,布洛芬（IBU）为模型药物,成功制备出PLA载IBU微球,利用扫描电子显微镜（SEM）、X射线衍射仪（XRD）、差示扫描量热仪（DSC）、傅里叶变换红外光谱仪（FTIR）、热失重分析仪（TG）和紫外可见分光光度计分析了微球形貌、结构和性能。结果表明,PLA/IBU微球呈表面多孔的无定形结构,分散性较好,IBU以分子或无规则状态负载在PLA中,化学结构未有变化,稳定性较纯IBU有所提高。在体外缓释测试中,PLA/IBU微球相比较纯IBU具有良好的缓释效果,随着投药量的增加,IBU的释放速率和累计释放量逐渐提高,含16 %IBU的PLA微球在48 h内累计释放量可达52 %。静电喷雾法制备的PLA/IBU微球有望提高IBU的生物利用度和溶出率,在生物医药领域具有潜在的应用前景。     

载阿霉素聚乳酸多孔微球的表征及释药性能

以阿霉素（DOX）为小分子化学药物模型,采用吸附法对聚乳酸（poly-L-lactide,PLLA）多孔微球进行载药,采用场发射扫描电子显微镜（FE-SEM）、傅里叶变换红外光谱（FTIR）、X射线衍射（XRPD）及差示扫描量热（DSC）对DOX-PLLA复合微球的形貌粒径及空气动力学性能、药物及材料的理化性能、载药性能进行表征,并且研究了其载药量、包封率和体外释放性能。结果表明,不同载药量之间的PLLA多孔微球粒径并无显著差异,均具有良好的空气动力学性能,适合肺部可吸入给药的条件;化学组成未见明显改变,物理结构由结晶态变为无定形态;随载药量的增加（2.9%,4.0%,4.6%）,包封率逐渐降低（56%,51%,44%）;药物的体外释放与原料药相比具有一定的缓释效果,最长释放时间可达5天,表明DOX-PLLA复合微球有望作为缓释制剂用于肺部给药。     

Effect of proteolytic enzymes in gastrointestinal fluids on drug release from polyelectrolyte complex microspheres based on partially phosphorylated chitosan

This study investigated the effect of proteolytic enzymes on in vitro release of ibuprofen from phosphorylated chitosan (PCS) microspheres in simulated gastric fluid (SGF) (pH 1.4) and simulated intestinal fluid (SIF) (pH 7.4). To reduce the enzymatic degradability and to enhance the sustained release property, polyelectrolyte complex microspheres based on PCS were developed and characterized. The ibuprofen release from PCS microspheres was found to be sustained more effectively than that from CS microspheres in the medium containing proteolytic enzymes. It was concluded that the PCS microspheres can be used more successfully as sustained oral drug‐delivery vehicles than CS microspheres due to their lesser enzymatic degradability. Copyright © 2004 Society of Chemical Industry     

Enhanced gastric retention and drug release via development of novel floating microspheres based on Eudragit E100 and polycaprolactone: synthesis and in vitro evaluation

Eudragit E 100 and polycaprolactone (PCL) floating microspheres for enhanced gastric retention and drug release were successfully prepared by oil in water solvent evaporation method. Metronidazole benzoate, an anti-protozoal drug, was used as a model drug. Polyvinyl alcohol was used as an emulsifier. The prepared microspheres were observed for % recovery, % degree of hydration, % water uptake, % drug loading, % buoyancy and % drug release. The physico-chemical properties of the microspheres were studied by calculating encapsulation efficiency of microspheres and drug release kinetics. Drug release characteristics of microspheres were studied in simulated gastric fluid and simulated intestinal fluid i.e., at pH 1.2 and 7.4 respectively. Fourier transform infrared spectroscopy was used to reveal the chemical interaction between drug and polymers. Scanning electron microscopy was conducted to study the morphology of the synthesized microspheres.     

Amino-Modified Polylactic Acid Nanofibre Microspheres as Drug Sustained Release Carriers for Alendronate

Amino-modified polylactic acid (EPLA) nanofibre microspheres with a high porosity, large specific surface area, strong adsorption capacity, and rich in active amino groups were developed for drug delivery applications. Alendronate, a well-known antiresorptive agent, was chosen as a model drug to evaluate the loading capacity and release properties of the prepared EPLA microspheres. SEM micrographs clearly showed that the drug was loaded into the microspheres within the pores between the nanofibers and as well as being adsorbed on their surface. XRD and FTIR spectra analyses also confirmed drug loading. UV/Vis-absorption spectrophotometry was used to study the impact of various parameters, including adsorption time and initial concentration and pH value of the alendronate solution, on the microsphere drug-loading capacity. Under optimum conditions, EPLA microspheres exhibited a high alendronate adsorption capacity of up to 503?mg/g. In vitro release studies showed that alendronate-loaded EPLA nanofibre microspheres exhibited a perfect release performance, with alendronate being released in a sustained manner for approximately 15 days without any obvious initial burst. Therefore, EPLA nanofibre microspheres hold great potential as efficient, controlled release drug delivery carriers of alendronate.     

Preparation and evaluation of cellulose acetate butyrate and poly(ethylene oxide) blend microspheres for gastroretentive floating delivery of repaglinide

In this study, hollow microspheres of cellulose acetate butyrate (CAB) and poly(ethylene oxide) (PEO) were prepared by emulsion–solvent evaporation method. Repaglinide was successfully encapsulated into floating microspheres. Various formulations were prepared by varying the ratio of CAB and PEO, drug loading and concentration of poly(vinyl alcohol) (PVA) solution. Encapsulation of the drug up to 95% was achieved. The microspheres tend to float over the simulated gastric media for more than 10 h. The micromeritic properties of microspheres reveal the excellent flow and good packing properties. The % buoyancy of microspheres was found to be up to 87. SEM showed that microspheres have many pores on their surfaces. Particle size ranges from 159 to 601 μm. DSC and X‐RD revealed the amorphous dispersion in the polymer matrix. In vitro release experiments were performed in simulated gastric fluid. In vitro release studies indicated the dependence of release rate on the extent of drug loading and the amount of PEO in the microspheres; slow release was extended up to 12 h. The release data were fitted to an empirical equation to compute the diffusional exponent (n), which indicated that the release mechanism followed the non‐Fickian trend. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci 2007     

Robust Silica Aerogel Microspheres from Rice Husk Ash to Enhance the Dissolution Rate of Poorly Water-Soluble Drugs

The present paper demonstrates the capability of specially prepared robust silica aerogel microspheres (RSAMs) to enhance the dissolution rate of poorly water-soluble drugs. A sol-gel/mineral oil emulsion method has been developed for RSAMs from rice husk ash (RHA), a biogenic source. The particles were characterized for their Brunauer–Emmett–Teller (BET) specific surface area, Barrett, Joyner and Halenda (BJH) pore volume and pore diameter, and morphology by optical microscopy and scanning electron microscopy (SEM). The dissolution rate of ibuprofen, a poorly water-soluble drug, was investigated by adsorbing it onto RSAMs upon dissolving it in supercritical carbon dioxide (scCO₂) at 150?bar and 40°C. This resulted in a loading of ～0.13?g ibuprofen/g loaded RSAMs in 24?h. X-ray diffraction analysis was used to characterize the nature of the adsorbed ibuprofen onto RSAMs. It was observed that the loaded drug on the aerogels is in amorphous form. An in vitro drug-release kinetic studies confirmed a significant enhancement in the dissolution rate, namely ～100% of the loaded ibuprofen released as compared to that of ～11% of crystalline ibuprofen in 15?min.     

Fabrication and structural regulation of PLLA porous microspheres via phase inversion emulsion and thermally induced phase separation techniques

In this work, a facile, scalable technique was developed to produce biodegradable porous microspheres by combining an oil‐in‐oil (O/O) surfactant‐free phase inversion emulsion technique with thermally induced phase separation (TIPS) method. The effects of PLLA concentration, stirring speed, macromolecule weight, and organic solvents on the size and microstructure of microspheres were investigated by scanning electron microscopy (SEM). The results revealed a highly porous structured microsphere with controllable sizes and morphologies by tuning the synthesis conditions. The typical resulting PLLA microspheres consist of nanoscale topographic structured surface and highly microporous interior. The coarse nanotopography and microcellular inner structure lead to a high drug loading capacity up to 60% for the PLLA microspheres from THF. The cumulative release percentage of the ibuprofen could reach 80% for drug‐loaded microspheres with different microstructures. The fabricated PLLA microspheres would have potential applications in the field of drug delivery and tissue engineering. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017 , 134, 44885.     

Hydroxyapatite nanorod-assembled hierarchical microflowers: rapid synthesis via microwave hydrothermal transformation of CaHPO4 and their application in protein/drug delivery

Hydroxyapatite (HAP) nanostructured materials have attracted much attention due to their excellent biocompatibility and promising applications in various biomedical fields. In this study, a facile method has been developed to synthesize HAP with flower-like hierarchical nanostructures. The flower-like CaHPO₄ precursor is firstly synthesized using triethyl phosphate (TEP) as the organic phosphorus source by the solvothermal method. The HAP hierarchical microflowers constructed with nanorods are then fabricated through rapid microwave hydrothermal transformation of the CaHPO₄ precursor in NaOH aqueous solution. The as-prepared HAP nanorod-assembled hierarchical microflowers are explored to study the protein/drug loading and release properties using hemoglobin (Hb) and ibuprofen (IBU) as a model protein and drug, respectively. The experimental results indicate that the as-prepared HAP nanorod-assembled hierarchical microflowers have relatively large specific surface area, high biocompatibility, high protein/drug loading capacity and pH-dependent sustained release properties. Thus, the as-prepared HAP nanorod-assembled hierarchical microflowers are promising for the applications in protein/drug delivery.     

聚乳酸-羟基乙酸聚合物载入羟基喜树碱载药纳米粒子的制备及表征

以抗癌药物羟基喜树碱作为模型药物,可降解材料聚乳酸-羟基乙酸(PLGA)为药物负载体,采用溶剂-抗溶剂沉淀法制备聚乳酸-羟基乙酸/羟基喜树碱的载药纳米微球,考察不同溶剂-反溶剂体系对载药包封效果的影响。结果表明,以丙酮-水为溶剂体系制备的载药微球性能较好,形貌外观呈圆球形,球表面圆润光滑,粒度均一,分散效果良好,平均粒径为160 nm,载药微球包封率随着载药量的增加而减小,实测载药量为7.83%的PLGA载药微球,其载药包封率为87.68%,在28 d后溶出累计量约50%,可见以聚乳酸-羟基乙酸为载体制备的羟基喜树碱剂型,缓释作用良好。     

一种双亲性共网络树脂的制备及其应用

用聚乙二醇二丙烯酸酯与甲基丙烯酸十八酯进行自由基共聚合反应,得到一种双亲性共网络树脂。对树脂结构进行了表征和亲油与亲水性能研究,并将其用作药物载体。结果发现,树脂同时具有亲油和亲水性能,对油品三氯甲烷的亲油倍率可达16.6 g/g;随着引入亲水基团的增加,树脂的亲水倍率逐渐增加;载体对于布洛芬有良好的负载率和缓释效果。通过热重分析表明,树脂在通常使用条件下具有很好的稳定性。     

Sustained-release ibuprofen prodrug particle: Emulsifier and initiator regulate the diameter and distribution

Polymers have played a vital part in the development of drug delivery systems (DDS). For DDS, having a controllable diameter and distribution are conducive to reproducibility of drug release behavior and efficacy. In this work, an ibuprofen prodrug (Ibu@PMMA) was synthesized by methyl methacrylate (MMA), ibuprofen monomer (Ibu@HEMA), and ethylene glycol dimethacrylate (EGDMA) via emulsion polymerization. The Ibu@PMMA exhibits spherical shapes, and its structural properties were characterized by NMR, FTIR, and SEM techniques. In addition, the hydrodynamic diameter and polydispersity index (PDI) of Ibu@PMMA were reduced by increasing the proportion of emulsifier. Meanwhile, by increasing the amount of initiator, the hydrodynamic diameter and PDI of Ibu@PMMA were decreased. Moreover, Ibu@PMMA exhibits good sustained-release ability in vitro, which could be used as a potential delivery system for anti-inflammatory agents.     

Hydrothermal synthesis of hierarchical hydroxyapatite: Preparation, growth mechanism and drug release property

Hydroxyapatite (HAP) hierarchical microspheres were synthesized by a facile hydrothermal method using calcium nitrate and ammonium dihydrogen phosphate through controlling complexing agents. The influences of two kinds of complexing agents (potassium sodium tartrate tetrahydrate and trisodium citrate) and reaction time on the morphology of HAP crystals have been investigated. These results indicate that complexing agents have a great influence on the morphology of HAP. When potassium sodium tartrate tetrahydrate was used as complexing agent, HAP flowers were composed of the network of nanosheet building blocks. Well-crystallized HAP dandelions with nanorods radiating from the center can be obtained by the introduction of trisodium citrate. Broader XRD diffraction peaks imply a nanometer scale size. Based on XRD and SEM results, the formation mechanism of HAP crystals has been discussed. The hierarchically structured HAP microspheres were explored as drug carriers. The results indicate that HAP flowers and dandelions showed a favorable sustained release property for ibuprofen; thus, they are very promising for application in drug delivery.     

单分散性PLGA磁性微球制备及其缓释性研究

为获得单分散性PLGA磁性微球,文中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,考察流速比和油相与内水相体积比对微球制备的影响。借助FTIR、SEM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：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60h内表现出阶段性匀速释放,且有较好磁响应性,有望用于磁响应性药物载体。     

载牛血清白蛋白凝胶微球体液环境下释药性能的研究

研究可在体内缓释并口服的蛋白多肽类药物是国内外医药界目前广泛关注的问题。利用毒性较低但力学性能差的海藻酸钠和水溶性较低但机械性能良好的聚乙烯醇共混制备凝胶微球,在模拟体液环境(p H=7.4),以空白微球作对照,来对载牛血清白蛋白凝胶微球进行释药性能研究,可看到凝胶微球在白蛋白药物的控释方面是有良好效果的,4 h时可达到牛血清白蛋白药物释放增速最快,12 h时牛血清白蛋白药物累计释放达到55%,这可以为可口服的蛋白多肽类药物口服体内靶向缓释的临床应用提供相关的参考依据,具有重大意义。