Properties of magnetic poly(glycidyl methacrylate) and poly(N-isopropylacrylamide) microspheres

Iron oxide colloids were prepared by coprecipitation of Fe(II) and Fe(III) salts in alkaline media and stabilized by perchloric acid, oleic acid, or poly(acrylic acid). In an attempt to obtain magnetic polymer microspheres differing in size, dispersion polymerization of glycidyl methacrylate (GMA) in ethanol containing HClO₄-stabilized magnetite, dispersion copolymerization of GMA and 2-hydroxyethyl methacrylate (HEMA) in toluene/2-methylpropan-1-ol mixture in the presence of oleic acid-coated magnetite, and inverse suspension copolymerization of N-isopropylacrylamide (NIPAAm) and N,N′-methylenebisacrylamide (MBAAm) in cyclohexane in the presence of poly(acrylic acid)-coated maghemite were compared. The microspheres were characterized by morphology, size, polydispersity, and some magnetic properties.     

Oral-based controlled release formulations using poly(acrylic acid) microgels

Aim: To investigate the release of hydrophobic and hydrophilic substances from tablets containing Pemulen and Carbopol as excipients. Method: The dissolution patterns of a hydrophobic (diazepam) and a hydrophilic active substance (midodrine-HCl) from different tablet formulations containing a nonmodified polyacrylic microgel (Carbopol 981 F) or a hydrophobically modified polyacrylic microgel (Pemulen®) have been studied. Possible differences in dissolution in phosphate buffer (pH 6.8) and in 0.1 M HCl between tablets produced using wet granulation and direct compression were also investigated. Results: Tablets produced by wet granulation had a greater effect on the release of active substance from the tablets. No major differences were observed in the release patterns of the hydrophilic substance midodrine-HCl from wet granulated tablets based on Carbopol and Pemulen. However, the release pattern of the more hydrophobic drug substance, diazepam, differed considerably between the two polymers. Wet granulation gave reproducible release patterns. The release patterns from the polymers differed considerably at pH 6.8 but were similar at low pH. Conclusions: The release of the diazepam from the hydrophobic polymer Pemulen was very slow, and the release was close to zero order.     

马来酸酐封端聚丙撑碳酸酯及其性能研究

以马来酸酐(MA)为封端剂对聚丙撑碳酸酯(PPC)进行了封端,采用红外光谱、凝胶渗透色谱、热失重分析和差示扫描量热分析等对封端前后样品的性能进行了表征.红外光谱分析确认了马来酸酐参与了封端反应,聚合物分子量的测试表明,封端过程中有扩链反应的发生,热失重分析结果表明,马来酸酐封端能较大地提高聚丙撑碳酸酯的热分解温度.     

Antibiotic drug release behavior of poly (vinyl alcohol)/sodium alginate hydrogels

Poly (vinyl alcohol)/sodium alginate hydrogels were prepared by freeze-thaw followed by calcium ion crosslinking. Chloramphenicol release behavior from the poly (vinyl alcohol)/sodium alginate hydrogels in mimic conditions of gastrointestinal tract was examined. The effects of composition, number of freeze-thaw cycles and calcium ion concentration on drug release process were investigated. The results showed that the cumulative release amount of chloramphenicol from the hydrogels (crosslinked through 4 freeze-thaw cycles and immersed in 2 % calcium chloride solution) decreased from 84.3 % to 72.3 % as sodium alginate content increased from 0 % to 75 %. For the hydrogels containing 50 % sodium alginate and immersed in 2 % calcium chloride solution after the freeze-thaw cycles, cumulative release amount of chloramphenicol decreased from 83.5 % to 76.6 % as the freeze-thaw cycles increased from 2 to 6. Cumulative release amount of chloramphenicol from the hydrogels containing 50 % sodium alginate and with 4 freeze-thaw cycles decreased from 79.8 % to 75.6 % when concentration of calcium chloride solution increased from 1 % to 4 %.     

Investigation of swellable poly (N-isopropylacrylamide) based hydrogels for drug delivery

The thermo-sensitive properties of poly (N-isopropylacrylamide) (PNIPA) hydrogels are modified by the addition of hydrophilic acrylamide comonomers and an interpenetrating network of sodium alginate for drug delivery applications near 37 °C. A mathematical model is presented to describe the mass transport kinetics during the hydrogel drug delivery process, which is accompanied by a volume change during phase transition. In this model, the transport in the polymer matrix is described by Fick's second law in cylindrical coordinates, with concentration dependent diffusion coefficients. The moving boundary problems caused by the polymer matrix swelling are also solved by numerical simulation. The models show that the Trypan blue release from the modified PNIPA-based hydrogels is strongly concentration dependent. The sodium alginate component is also shown to effectively facilitate the diffusion process. The results from the simulation are in good agreement with the measurements of diffusion and swelling observed from in vitro experiments. The implications of this work are also discussed for practical drug delivery systems.     

聚乳酸接枝马来酸酐/丙烯酸丁酯共聚物的制备与性能

以马来酸酐(MAH)和丙烯酸丁酯(BA)为单体,通过溶液接枝法制备了聚乳酸(PLA)接枝MAH/BA共聚物(m PLA)。使用红外光谱(FT-IR)、广角X射线衍射(WAXD)、差示扫描量热仪(DSC)、热重分析仪(TG)研究了接枝共聚物的结构和性能。结果表明,随着单体质量比BA/MAH的增加,单体在PLA上的接枝率出现先增大后减小的趋势,当m(MAH)/m(BA)=1/1,m(MAH)/m(PLA)=3/100时,制备的m PLA接枝率最高为1.96%;与纯PLA相比,m PLA的结晶度和热稳定性均比有所下降,且样品的接枝率越大其结晶度越低;随着单体中BA含量的增加,m PLA的熔融温度和玻璃化转变温度有减小的趋势。     

Polyethyleneimine modified biocompatible poly(N-isopropylacrylamide)-based nanogels for drug delivery

A series of biocompatible and stimuli-sensitive poly(N-isopropylacrylamide-co-propyl acrylic acid) (P(NIPAAm-co-PAAc)) nanogels were synthesized by emulsion polymerization. In addition, polyethyleneimine (PEI) was further grafted to modify the PNIPAAm-based nanogels. The P(NIPAAm-co-PAAc)-g-PEI nanogels exhibited good thermosensitivity as well as pH sensitivity. Transmission electron microscopy (TEM) showed that the P(NIPAAm-co-PAAc)-g-PEI and P(NIPAAm-co-PAAc) nanogels displayed well dispersed spherical morphology. The mean sizes of the nanogels measured by dynamic light scattering (DLS) were from 100 nm to 500 nm at different temperatures. The cytotoxicity study indicated P(NIPAAm-co-PAAc) nanogels exhibited a better biocompatibility than both PNIPAAm nanogel and P(NIPAAm-co-PAAc)-g-PEI nanogel although all the three kinds of nanogels did not exhibit apparent cytotoxicity. The drug-loaded nanogels, especially the PEI-grafted nanogels, showed temperature-trigged controlled release behaviors, indicating the potential applications as an intelligent drug delivery system.     

Smart magnetic poly(N-isopropylacrylamide) to control the release of bio-active molecules

Thermo switchable magnetic hydrogels undoubtedly have a great potential for medical applications since they can behave as smart carriers able to transport bioactive molecules to a chosen part of the body and release them on demand via magneto-thermal activation. We report on the ability to modify the lower critical solution temperature (LCST) of poly(N-isopropylacrylamide) (PNIPAM) on demand from 32 °C to LCST ≥37 °C. This was achieved by the absorption of controlled amounts of magnetite nanoparticles on the polymer chains. We show, through the effect on cell viability, that the resulting magnetic PNIPAM is able to trap and to release bio-active molecules, such as cell growth factors. The activities of the released bio molecule are tested on human umbilical vein endothelial cells culture. We demonstrate that the LCST of the magnetic PNIPAM can be reached remotely via inductive heating with an alternating magnetic field. This approach on magnetic PNIPAM clearly supports appealing applications in safe biomedicine.     

Poly (N-isopropylacrylamide) microgels for organic dye removal from water

The ability of poly (N-isopropylacrylamide) (pNIPAm), and pNIPAm-co-acrylic acid (pNIPAm-co-AAc) microgels to remove an organic azo dye molecule, 4-(2-Hydroxy-1-naphthylazo) benzenesulfonic acid sodium salt (Orange II) from aqueous solutions at both room and elevated temperature was assessed. At room temperature, we found that the amount of Orange II removed from water (removal efficiency) increased with increasing AAc and microgel concentration. The removal of Orange II from water was also fit by a Langmuir sorption isotherm model. Furthermore, we found the extent of Orange II removal depended on solution temperature; more Orange II was removed from water at elevated temperature and as the microgels were held at that temperature for longer durations of time. Additionally, by increasing the cycles between high and ambient temperature, the removal of Orange II was enhanced, although this was only true for two temperature cycles. We hypothesize that this is a result of the thermoresponsive nature of pNIPAm-based microgels which deswell at elevated temperature expelling their solvating water and when the microgels are cooled back down they reswell with the Orange II containing water. We also hypothesize that the microgels become saturated after the second heating cycle and so the efficiency of removal did not increase further. Finally, we assessed the ability of the microgels to retain the Orange II after it is removed from the aqueous solution. We determined that the microgels "leak" 25.6% of the Orange II that was originally removed from the water.     

可降解聚碳酸亚丙酯马来酸酐的合成与表征

在负载双金属PBM型催化剂下,以二氧化碳(CO2),环氧丙烷(PO)和马来酸酐(MA)为原料,三元共聚反应合成了聚碳酸亚丙酯马来酸酐(PPCMA).采用FTIR、1H-NMR、13C-NMR、DSC等对PPCMA进行了表征.结果表明,产物中引入了马来酸酐单元且共聚过程中不发生双键交联和构型转化;同时,马来酸酐单元的引入有效地提高了聚合物的特性粘数[η],玻璃化转变温度T g以及热稳定性;且增强了材料的降解性;不同的聚合反应时间对PPCMA的特性粘数和粘均分子量有着明显的影响.     

Study on short ramie fiber/poly(lactic acid) composites compatibilized by maleic anhydride

Short ramie fiber reinforced poly(lactic acid) (PLA) composites without and with maleic anhydride (MA) were developed. The influence of PLA-g-MA as a compatibilizer on the properties of the composites was studied. The tensile, flexural and impact strength of the composites have improvements with the addition of PLA-g-MA. The morphology of fracture surface evaluated by SEM indicates that the composites with the addition of PLA-g-MA can get better adhesion between the fiber and the matrix. And the Vicat softening temperature and the degradation temperature of the composites are increased with the addition of PLA-g-MA. However, PLA-g-MA leads the glass transition temperature (T_g) decrease according to the DSC results.     

Probing the morphology and nanoscale mechanics of single poly(N-isopropylacrylamide) microgels across the lower-critical-solution temperature by atomic force microscopy

Submicrometer-sized particles of poly(N-isopropylacrylamide) (PNIPAM) are synthesized by surfactant-free radical polymerization. The morphology and nanomechanical properties of individual, isolated PNIPAM microgel particles at the silicon/air and silicon/water interfaces, below and above the PNIPAM volume-phase-transition temperature (VPTT), are probed by atomic force microscopy. In air, and in water below the VPTT, the PNIPAM spheres are flattened and adopt a pancakelike shape. Interestingly, above the VPTT the microgels adopt a more spherical form with increased height and decreased width, which is attributed to reduced interactions of the particles with the substrate. The elastic modulus calculated from force-indentation curves obtained for individual microgel spheres reveals that the stiffness of the particle's surface decreases by two orders of magnitude upon swelling in water. Additionally, the modulus of the PNIPAM spheres in water increases by one order of magnitude when crossing the VPTT from the swollen to the collapsed states, indicating a more compact chain packing at the particle surface.     

Intelligent anticancer drug delivery performances of two poly(N-isopropylacrylamide)-based magnetite nanohydrogels

This article evaluates the anticancer drug delivery performances of two nanohydrogels composed of poly(N-isopropylacrylamide-co-itaconic anhydride) [P(NIPAAm-co-IA)], poly(ethylene glycol) (PEG), and Fe₃O₄ nanoparticles. For this purpose, the magnetite nanohydrogels (MNHGs) were loaded with doxorubicin hydrochloride (DOX) as a universal anticancer drug. The morphologies and magnetic properties of the DOX-loaded MNHGs were investigated using transmission electron microscopy (TEM) and vibrating–sample magnetometer (VSM), respectively. The sizes and zeta potentials (ξ) of the MNHGs and their corresponding DOX-loaded nanosystems were also investigated. The DOX-loaded MNHGs showed the highest drug release values at condition of 41?°C and pH 5.3. The drug-loaded MNHGs at physiological condition (pH 7.4 and 37?°C) exhibited negligible drug release values. In vitro cytotoxic effects of the DOX-loaded MNHGs were extensively evaluated through the assessing survival rate of HeLa cells using the MTT assay, and there in vitro cellular uptake into the mentioned cell line were examined using fluorescent microscopy and fluorescence-activated cell sorting (FACS) flow cytometry analyses. As the results, the DOX-loaded MNHG1 exhibited higher anticancer drug delivery performance in the terms of cytotoxic effect and in vitro cellular uptake. Thus, the developed MNHG1 can be considered as a promising de novo drug delivery system, in part due to its pH and thermal responsive drug release behavior as well as proper magnetite character toward targeted drug delivery.     

Surface modification of polystyrene and poly(ethylene terephtalate) by grafting poly(N-isopropylacrylamide)

In this work, poly(N-isopropylacrylamide) (PNIPAAm) was incorporated into previously oxidized PS and PET surfaces by grafting using two photo-initiation pathways. The incorporation of PNIPAAm was observed by drop water contact angle measurements, dyeing with Methylene Blue and AFM images analysis of the virgin and modified polymers. It was verified that the grafting process depends on the chemical surface environment. The grafted surfaces are hydrophilic below 32 °C and hydrophobic above this temperature. The transition is due to the incorporated PNIPAAm. This characteristic gives to the grafted materials potential to be applied as biomaterials.     

Thermo-sensitive poly(N-isopropylacrylamide)/ mesoporous silica nanocomposites as controlled delivery carriers: loading and release behaviors for drug ibuprofen

Thermo-sensitive nanocomposites based on mesoporous silica SBA-15 and poly(N-isopropylacrylamide) (PNIPAAm) have been synthesized via in situ radical polymerization in mesopores. The resultant materials were used as carriers to construct temperature-responsive controlled drug delivery systems. Loading of model drug ibuprofen (IBU) was ascertained by IR and UV-vis/DRS spectroscopy, and the mesostructure and pore properties of the delivery system were characterized by small-angle XRD and N2 adsorption-desorption experiment. Study on drug uptake indicated that higher polymer content in the composite, higher IBU concentration in loading solution and lower loading temperature below the lower critical solution temperature (LCST) could increase the loading amount of IBU by means of interaction between IBU and polymer and trap effect of the polymer chains in pores. Different from the uptake of IBU, however, the release of drug followed a positive temperature-responsive manner, that is, the release was accelerated upon heating above the LCST, while decelerated and lasted for a longer period of time below the LCST. This feature allows the material to function as a reversible fast/slow transition switch or rate regulator responsive to environmental temperature and to be potentially interesting in controlled delivery and other smart application fields.     

星状聚(N-异丙基丙烯酰胺)的合成及性能研究

采用2-溴异丁酰溴与β-环糊精(-βCD)上羟基的适度反应得到了多溴代的-βCD(Br-βCD)。用Br-βCD引发N-异丙基丙烯酰胺(NIPAm)发生原子转移自由基聚合(ATRP),合成出约15臂的聚(N-异丙基丙烯酰胺)星状聚合物-βCD-(PNIPAm)15.4。用IR1、H-NMR表征了星状聚合物的结构,以8-苯胺基-1-萘磺酸(ANS)作客体分子,研究了星状聚合物的包合性,结果表明,-βCD-(PNIPAm)15.4具有热敏性和超分子包合性。     

温敏型聚合物PNIPAAM的合成及应用研究进展

聚N-异丙基丙烯酰胺(简称PNIPAAM)是一类研究广泛的温敏型功能高分子水凝胶.从制备方法、应用及其改性这三个方面综述了近年来对PNIPAAm的研究进展,并提出今后的发展方向.