Synthesis, characterization and sustaining controlled release effect of mesoporous SBA-15/ramipril composite drug

A loading of ramipril in SBA-15 (Santa Barbara Amorphous) mesoporous material was studied. (SBA-15)-ramipril composite material was characterized by chemical analysis, infrared spectroscopy, powder X-ray diffraction, low temperature N₂ adsorption–desorption at 77 K characterization techniques. Ramipril drug release processes from SBA-15 host to simulated body fluid (SBF), simulated gastric juice (SGJ), simulated intestinal fluid (SIF) were monitored in a simulated way and actions of the sustained release of (SBA-15)-ramipril was studied. The results showed that the loading amount of ramipril drug in SBA-15 was 90.30 mg/g. The cumulative sustained release rate of ramipril composite drug in SBF achieved 99.7 % after 27 h. When the sustained release of composite drug in SGJ was 8 h, the maximum cumulative sustained release ratio achieved 54.9 %. When the sustained release of composite drug was 9 h in SIF, the maximum cumulative sustained release ratio achieved 34.9 %. The method described in this study is suitable for carrying ramipril drug on SBA-15, and a new carrier to load ramipril drug was found. Meanwhile, the efficacy of ramipril drug and time efficacy could be improved.     

酮洛芬/酸改性蒙脱土缓释体系的制备及体外释药研究

以盐酸改性蒙脱土为药物载体,采用离子交换法制备了酮洛芬/酸改性蒙脱土(KPF/acid-MMT)复合物.借助X射线衍射(XRD)、比表面积分析和扫描电子显微镜(SEM)等手段对复合物进行了结构表征;采用透析法研究了介质pH值对KPF/acid-MMT释放性能的影响;运用3种数学模型对其体外释放行为进行拟合.结果表明:经酸改性后,蒙脱土的比表面积由19.66 m~2/g增加到202.84 m~2/g,载药量由18.09%提高到37.24%;在人工模拟胃液(pH=1.2)和人工模拟肠液(pH=6.8)中,酮洛芬的累积释放量分别为18.6%和86.7%;零级动力学模型能更好地拟合和描述KPF/acid-MMT在人工模拟肠液中的体外释放行为.酸改性蒙脱土能有效提高药物的负载量,KPF/acid-MMT可实现药物的定向释放和缓释性能,有望制成肠道缓释口服药物制剂.     

Preparation and characterization of porous titania-grafted poly(styrene-divinylbenzene)/maleic anhydride nanocomposite microspheres

Mesoporous titania-grafted poly(styrene-divinylbenzene)/maleic anhydride [P(St-DVB)/MA] nanocomposite microspheres were prepared by an open ring reaction method.The titania nanoparticles were first modified by attachment of amino groups to their surface to prevent particle aggregation,and to allow the nanoparticles to covalently bond the polymer microspheres,the surface of which was modified by attachment of MA functional groups to enable the polymer to retain their porous structures and to react with the a...     

聚合物模板辅助镍微球的水热制备

以三嵌段共聚物HO(CH₂CH₂O)₂₀(CH₂CH(CH₃)O)₇₀(CH₂CH₂O)₂₀H (P123)为模板剂, 次亚磷酸钠为还原剂, 水热制备了微米级镍微球. 采用X射线衍射(XRD)、扫描电镜(SEM)和振动样品磁强计(VSM)对产物进行表征. 结果表明, 镍微球由纳米级的镍微晶组成, 其中至少部分微球存在空心结构. 微球的尺寸随着前驱体溶液pH值的增加而减小, 其聚集成链的程度随着水热温度的上升而增强. 120和220 ℃水热合成微球的直径范围、平均微晶尺寸和矫顽力分别是1.5～4.5和0.8～4.5 μm, 16.0和14.2 nm, 以及91.5和66.1 Oe.     

Photochemical construction of nanoporous polymer microspheres in Cu/Cu2O nanoparticle suspensions

Taking the poly(styrene-co-acrylamide) (P(St-AM)) as a model material, a novel two-step photochemical method was introduced to construct nanoporous polymer microspheres at room temperature. Under ultraviolet light irradiation, suspensions composed of Cu/Cu₂O nanoparticles were first prepared in an alcohol solution of acetylacetonate and benzophenone. Subsequently, the monomers were photopolymerized around the nanoparticles in the suspension-added precursor solution to form polymer–nanoparticle composite microspheres. Nanoporous polymer microspheres could then be obtained by removing the particles with acid. The products had been investigated by XRD, SEM, TEM, IR, DSC, and BET. Results showed the typical microspheres had diameters of 200~300?nm, and the specific areas and pore volume regularly varied with the quantity of the suspensions. By the optimum control, porous P(St-AM) microspheres with average pore size of 5.7?nm, pore volume of 0.18?cm³/g, and specific surface area of 123.54?m²/g could be obtained. The method represents a new, easily manipulated, cost-effective, and safe route for preparation of porous polymer microspheres using inorganic porogens.     

One step synthesis,characterization of F127-Mn+-chlorpyrifos mesoporous silica for sustained release system with pH sensitivity

The triblock copolymer F127 (molecular formula (EO)₁₀₆(PO)₇₀(EO)₁₀₆) was adopted as template with TMOS as the silica source. They were hydrolyzed by acidic aqueous solution in which chlorpyrifos (CH) and metal ions (Mⁿ⁺) were introduced to the products to construct "F127-Mⁿ⁺-CH" coordination structure in one step. Different sustained release systems were prepared through changing the composition of acidic aqueous solution added during the preparation. The characterization results confirmed the coordination interaction existing among metal ions, mesoporous silica and chlorpyrifos. It was also proved that the chlorpyrifos loaded in the sustained release system existed as amorphous state. According to SEM and TEM observation, the pore of the material presented as face-centered cage-type cubic structure with IM-3M symmetry similar to SBA-16 which is in accordance with N₂ adsorption isotherms. The as-synthesized system showed significant pH sensitivity in the sustained release process indicating that the sustained release system can be well stored in neutral environment and activated while sprayed into earth in acid or basic environment. Their sustained release curves can be described by Korsmeyer-Peppas equation in neutral while accords with Higuchi under acid or basic environment.     

Encapsulation and characterization of flurbiprofen loaded poly(є-caprolactone)–poly(vinylpyrrolidone) blend micropheres by solvent evaporation method

Flurbiprofen loaded PCL/PVP blend microspheres were prepared by o/w solvent evaporation method using various concentrations of gelatin as emulsifying agent. Microsphere recovery decreased with a decrease in the concentration of the emulsifier in the dispersion. Encapsulation efficiency and drug loading of microspheres increased with decrease in concentration of emulsifying agent. Hydration rate, encapsulation efficiency and drug loading of microspheres increased with increase in concentration of PVP. Rheological properties showed free flowing nature of microspheres. SEM (Scanning electron microscope) revealed microspheres were discrete, spherical and became porous with decrease in concentration of emulsifying agent but smooth with higher concentration of emulsifying agent. FTIR (Fourier transform infrared spectroscopy) spectra of pure and encapsulated flurbiprofen in all formulation showed no significant difference in characteristic peaks, suggesting stability of flurbiprofen during encapsulation process. X-RD (X-ray powder diffractometry) of pure flurbiprofen shows sharp peaks, which decreases on encapsulation, indicating dispersion at molecular level and hence decrease in the crystallinity of drug in microspheres. Microspheres showed an enteric nature at pH 1.2 and a sustained release pattern at pH 6.8. Rapid drug release was observed in microspheres with higher concentration of PVP (polyvinylpyrrolidone), PVP acts as channeling agent. Formulation with low concentration of emulsifying agent also showed a fast release due to porous structure. Drug release kinetics followed zero order at pH 1.2 while at pH 6.8 Higuchi model was best fitted and was found non fickian.     

Novel PLGA Microspheres for Sustained Delivery of Antisense Oligonucleotide

Novel poly(lactide-co-glycolide acid)(PLGA) microspheres were developed for sustained delivery of antisense oligonucleotide(ASO). First, a new cationic agent, polyethylenimine(PEI) conjugated to linoleic acid(LA)(PEI-LA) was synthesized by reacting PEI(M_w=800) with linoleoyl chloride. Then, PEI-LA was combined with LOR-2501 to form electrostatic complexes at moderate nitrogen-to-phosphate(N/P) molar ratios which were then encapsulated into poly(lactide-co-glycolide) microspheres by a multiple emulsion-solvent evaporation technique. With an increase in ASO/PEI-LA concentration from 5% to 10%, encapsulation efficiency of ASO in the microspheres reduced from 72.14% to 57.62%, and the particle size of microspheres increased from 28.58 μm to 34.76 μm. In vitro studies show that the release profile of ASO from microspheres prepared at 7.5% ASO-PEI-LA lasted for 14 d. The novel microspheres have a potential use as a sustained release vehicle for ASO.     

Drug Delivery Systems Based on Porous Chitosan/Polyacrylic acid Microspheres

Porous microspheres have been prepared by suspension free radical polymerization of acrylic acid (AA) in the presence of chitosan (CHI). The microspheres were characterized by FTIR and environmental SEM. The PAA content of the microspheres was estimated to be in the range 45–50 wt.‐%. The swelling degree of these particles is almost constant in the range 2 < pH < 5, but it increases considerably as the pH is raised from 5 to 10. The release profiles of microspheres loaded with meclofenamic acid (MF) were determined at pH 2, 7.4, and 10. The in vitro release of MF at different pHs was modulated by the solubility of the drug. These microcapsules are biodegradable and presented good biocompatibility and biodegradability during in vivo experiments.

ESEM microphotograph of the porous PAA/CHI microspheres.     

Yolk‐Shell Porous Microspheres of Calcium Phosphate Prepared by Using Calcium L‐Lactate and Adenosine 5′‐Triphosphate Disodium Salt: Application in Protein/Drug Delivery

A facile and environmentally friendly approach has been developed to prepare yolk‐shell porous microspheres of calcium phosphate by using calcium L ‐lactate pentahydrate (CL) as the calcium source and adenosine 5′‐triphosphate disodium salt (ATP) as the phosphate source through the microwave‐assisted hydrothermal method. The effects of the concentration of CL, the microwave hydrothermal temperature, and the time on the morphology and crystal phase of the product are investigated. The possible formation mechanism of yolk‐shell porous microspheres of calcium phosphate is proposed. Hemoglobin from bovine red cells (Hb) and ibuprofen (IBU) are used to explore the application potential of yolk‐shell porous microspheres of calcium phosphate in protein/drug loading and delivery. The experimental results indicate that the as‐prepared yolk‐shell porous microspheres of calcium phosphate have relatively high protein/drug loading capacity, sustained protein/drug release, favorable pH‐responsive release behavior, and a high biocompatibility in the cytotoxicity test. Therefore, the yolk‐shell porous microspheres of calcium phosphate have promising applications in various biomedical fields such as protein/drug delivery.     

Ag-polymer composite microspheres with patterned surface structures

Novel silver-poly(acrylamide-co-methacrylic acid) [Ag-P(AM-co-MAA)] composite microspheres, in tens of micrometer size range, with patterned surface and core/shell structures were prepared by chemical reduction of Ag₂CrO₄-P(AM-co-MAA) composite microspheres in ethanol. Characterization with various techniques revealed that the chemical composition of the “shell” is dominated by Ag, but the “core” is dominated by the template, P(AM-co-MAA). It was also demonstrated that the surface morphology of the Ag-polymer composite microspheres is similar to that of their precursors and can be controlled to a certain extent by varying the composition of template copolymer, approaches, and amount of Ag₂CrO₄ deposited. This morphology transfer technique is also applicable for other silver salts-polymer composite microspheres. The same silver-polymer composite microspheres with very different morphology have also been prepared by utilizing this technique, but the different precursor microspheres, Ag₃PO₄-P(AM-co-MAA), were used. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

PMAA microgel surface-supported phase transfer catalyst as reusable microreactors for ultra-deep desulfurization

The reusable microreactors, poly(methacrylic acid) (PMAA) microgels surfacely covered with 3-(trimethoxysilyl)-propyldimethyloctadecyl ammonium chloride (AEM) and K₂{W(=O)(O₂)₂(H₂O)}₂ (W2) complexes, have been synthesized by using an ion exchange reaction between AEM located on PMAA microgels and W2 in aqueous solution. The final composite microspheres and intermediate products are characterized by scanning electron microscopy, Fourier transform infrared spectroscopy, energy dispersive X-ray spectrophotometer, and thermogravimetric analysis, respectively. The results indicated the PMAA/AEM/W2 composite microspheres with surface-wrinkling morphology and core-shell structure. The feasibility of the composite microspheres used as reusable microreactors in catalytic oxidation of dibenzothiophene (DBT) was investigated. Additionally, the effects of some factors, including the amount of the microreactors, temperature, H₂O₂/DBT molar ratio, the loaded amount of AEM, DBT concentration, and recycling times, on the catalytic oxidation were examined. The results demonstrated that the prepared composite microspheres possess high catalytic performance and reusability in the catalytic oxidation of DBT.     

Study on Fe3O4/polyaniline electromagnetic composite hollow spheres prepared against sulfonated polystyrene colloid template

Fe₃O₄/polyaniline (PANI) composite hollow spheres were prepared by using sulfonated polystyrene (SPS) microspheres as templates. The sulfonic acid groups were applied to induce absorbing Fe₃O₄ nanoparticle, and subsequently, conductive PANI was grown. Finally, the polystyrene cores were selectively dissolved to yield composite hollow microspheres with electromagnetic properties. The analysis results indicated that the adsorption of Fe₃O₄ on template core by electrostatic interaction resulted in magnetic composite microspheres. The conductivity of composite hollow spheres was remarkably increased after polyvinylpyrrolidone modification which favored the growth of PANI on SPS/Fe₃O₄ and enhanced the integrity of hollow microspheres. The saturated magnetization of the composite hollow microspheres was tuned from 2.7 to 9.1 emu/g, and the conductivity was in the range from 10^?2 to 10⁰?S/cm.     

Core–Shell Hollow Microspheres of Magnetic Iron Oxide@Amorphous Calcium Phosphate: Synthesis Using Adenosine 5′‐Triphosphate and Application in pH‐Responsive Drug Delivery

Drug nanocarriers with magnetic targeting and pH‐responsive drug‐release behavior are promising for applications in controlled drug delivery. Magnetic iron oxides show excellent magnetism, but their application in drug delivery is limited by low drug‐loading capacity and poor control over drug release. Herein, core–shell hollow microspheres of magnetic iron oxide@amorphous calcium phosphate (MIO@ACP) were prepared and investigated as magnetic, pH‐responsive drug nanocarriers. Hollow microspheres of magnetic iron oxide (HMIOs) were prepared by etching solid MIO microspheres in hydrochloric acid/ethanol solution. After loading a drug into the HMIOs, the drug‐loaded HMIOs were coated with a protective layer of ACP by using adenosine 5′‐triphosphate (ATP) disodium salt (Na₂ATP) as stabilizer, and drug‐loaded core–shell hollow microspheres of MIO@ACP (HMIOs/drug/ACP) were obtained. The as‐prepared HMIOs/drug/ACP drug‐delivery system exhibits superparamagnetism and pH‐responsive drug‐release behavior. In a medium with pH 7.4, drug release was slow, but it was significantly accelerated at pH 4.5 due to dissolution of the ACP shell. Docetaxel‐loaded core–shell hollow microspheres of MIO@ACP exhibited high anticancer activity.     

Entrapment of Protein Using Electrosprayed Poly(d,l‐lactide‐co‐glycolide) Microspheres with a Porous Structure for Sustained Release

The entrapment of a protein in porous poly(d,l ‐lactide‐co‐glycolide) (PLGA) microspheres is demonstrated through the closure of their outer surface pores for sustained delivery of the protein. The porous PLGA microspheres with less than 10 μm in size are prepared by electrospraying. Aqueous solutions containing fluorescein isothiocyanate‐dextran or bovine serum albumin (BSA) are penetrated into the inner pores as a result of vacuum treatment, and the outer surface pores of the porous PLGA microspheres are then closed using a solvent (dimethyl sulfoxide) to ensure entrapment of the macromolecules. Confocal microscopy images confirm the presence of a large amount of the macromolecules inside the porous structure. Circular dichroism spectroscopy and release analysis reveal that BSA is entrapped without denaturation and released in a sustained manner for a period of over 2 months, respectively.

     

Ultrasonic Preparation of Hierarchical Graphene‐Oxide/TiO2 Composite Microspheres for Efficient Photocatalytic Hydrogen Production

Hierarchical graphene oxide (GO)‐TiO₂ composite microspheres with different GO/TiO₂ mass ratios were successfully prepared by mixing GO and TiO₂ microspheres under ultrasonic conditions. Ultrasonication helped the GO and TiO₂ microsphere to uniformly mix on the microscale. The results showed that the GO‐TiO₂ composites that were prepared by ultrasonic mixing exhibited significantly higher hydrogen‐evolution rates than those that were synthesized by simple mechanical grinding, owing to synergetic effects, including enhanced light absorption and scattering, as well as improved interfacial charge transfer because of the excellent contact between the GO sheets and TiO₂ microspheres. In addition, GO‐TiO₂‐3 (3 wt. % GO) showed the highest hydrogen‐generation rate (305.6 μmol h^?), which was about 13 and 3.3‐times higher than those of TiO₂ microsphere and GO‐P25 (with 3 wt. % GO), respectively. Finally, a tentative mechanism for hydrogen production is proposed and supported by photoluminescence and transient photocurrent measurements. This work highlights the potential applications of GO‐TiO₂ composite microspheres in the field of clean‐energy production.     

Hydroxyapatite Hierarchically Nanostructured Porous Hollow Microspheres: Rapid,Sustainable Microwave‐Hydrothermal Synthesis by Using Creatine Phosphate as an Organic Phosphorus Source and Application in Drug Delivery and Protein Adsorption

Hierarchically nanostructured porous hollow microspheres of hydroxyapatite (HAP) are a promising biomaterial, owing to their excellent biocompatibility and porous hollow structure. Traditionally, synthetic hydroxyapatite is prepared by using an inorganic phosphorus source. Herein, we report a new strategy for the rapid, sustainable synthesis of HAP hierarchically nanostructured porous hollow microspheres by using creatine phosphate disodium salt as an organic phosphorus source in aqueous solution through a microwave‐assisted hydrothermal method. The as‐obtained products are characterized by powder X‐ray diffraction (XRD), Fourier‐transform IR (FTIR) spectroscopy, SEM, TEM, Brunauer–Emmett–Teller (BET) nitrogen sorptometry, dynamic light scattering (DLS), and thermogravimetric analysis (TGA). SEM and TEM micrographs show that HAP hierarchically nanostructured porous hollow microspheres consist of HAP nanosheets or nanorods as the building blocks and DLS measurements show that the diameters of HAP hollow microspheres are within the range 0.8–1.5 μm. The specific surface area and average pore size of the HAP porous hollow microspheres are 87.3 m²g^?1 and 20.6 nm, respectively. The important role of creatine phosphate disodium salt and the influence of the experimental conditions on the products were systematically investigated. This method is facile, rapid, surfactant‐free and environmentally friendly. The as‐prepared HAP porous hollow microspheres show a relatively high drug‐loading capacity and protein‐adsorption ability, as well as sustained drug and protein release, by using ibuprofen as a model drug and hemoglobin (Hb) as a model protein, respectively. These experiments indicate that the as‐prepared HAP porous hollow microspheres are promising for applications in biomedical fields, such as drug delivery and protein adsorption.     

One-pot synthesis and characterization of crosslinked polyphosphazene dopamine microspheres for controlled drug delivery applications

Inorganic–organic hybrid and highly cross-linked poly(cyclotriphosphazene-co-dopamine) microspheres (PCTD) were successfully synthesized by a one-step precipitation polymerization technique. In the polymerization reaction, dopamine (a neurotransmitter), hexachlorocyclotriphosphazene (HCCP, N₃P₃Cl₆) and triethylamine (TEA) were used as a monomer, a crosslinker molecule and an acid acceptor, respectively. The characterization of PCTD microspheres was performed by SEM-EDX, FTIR, XRD, TGA and DLS. The particle size of microspheres were determined as 1.042?µm. The usability of synthesized novel polyphosphazene microspheres for controlled drug release was investigated using acriflavine as a model drug. Acriflavine has antimicrobial and anticancer properties. As drug release medium pH:7.4 (PBS) and pH: 5.0 buffer solutions were used. They were the pH of blood and the approximate pH of the environment in which the cancerous cells are located, respectively. PCTD microspheres have 19.5?mgg^?1 drug storage capacity and 29% (pH: 5.0) and 47% (pH: 7.4) of the acriflavine was released from PCTD microspheres at 37?°C during 7?days.     

Highly sensitive and selective detect of p‐arsanilic acid with a new water‐stable europium metal–organic framework

The p‐arsanilic acid (p‐ASA), as an aromatic organoarsenic compounds, had received considerable concerns for their potential toxicity and carcinogenic properties. It was essential to detect p‐ASA with a facile method. In this paper, an europium based fluorescent metal–organic framework (MOF) [Eu₂(clhex)·2H₂O)]·H₂O ( BUC‐69 ) was successfully prepared under hydrothermal conditions with 1,2,3,4,5,6‐cyclohexanehexacarboxylic acid (H₆clhex) as organic linker. BUC‐69 displayed superior fluorescence capability to achieve selective and sensitive detection toward p‐ASA in water, which presented the first example of a MOF‐based sensor to detect p‐ASA. BUC‐69 showed excellent chemical stability in solutions under pH ranging from 4 to 12, which makes it be a potential sensor both in acidity and alkalinity condition. Significantly, BUC‐69 performed well in fluorescent sensing of p‐ASA at a low concentration (10^?6 M) in the simulated wastewater prepared with real lake water, and the results were comparable to the values detected by Inductively Coupled Plasma Optical Emission Spectrometer (ICP‐OES). The corresponding mechanism of fluorescent sensing toward p‐ASA with BUC‐69 was proposed and affirmed.     

Composite microparticle drug delivery systems based on chitosan, alginate and pectin with improved pH-sensitive drug release property

Composite microparticle drug delivery systems based on chitosan, alginate and pectin with improved pH sensitivity were developed for oral delivery of protein drugs, using bovine serum albumin (BSA) as a model drug. The composite drug-loaded microparticles with a mean particle size less than 200 μm were prepared by a convenient shredding method. Since the microparticles were formed by tripolyphosphate cross-linking, electrostatic complexation by alginate and/or pectin, as well as ionotropic gelation with calcium ions, the microparticles exhibited an improved pH-sensitive drug release property. The in vitro drug release behaviors of the microparticles were studied in simulated gastric (pH 1.2 and pH 5.0), intestinal (pH 7.4) and colonic (pH 6.0 and pH 6.8 with enzyme) media. For the composite microparticles with suitable compositions, the releases of BSA at pH 1.2 and pH 5.0 could be effectively sustained, while the releases at pH 7.4, pH 6.8 and pH 6.0 increased significantly, especially in the presence of pectinase. These results clearly suggested that the microparticles had potential for site-specific protein drug delivery through oral administration.