A novel strategy for encapsulation and release of proteins: hydrogels and microgels with acid-labile acetal cross-linkers

A new acid-labile acetal cross-linker was synthesized and used to prepare protein-loaded hydrogels and microgels. This cross-linker undergoes an acid-catalyzed degradation with a half-life of 5.5 min at pH 5.0 and 24 h at pH 7.4. Protein-loaded hydrogels were synthesized with this cross-linker, and their release profiles were measured as a function of pH. Hydrogels made with the acetal cross-linker release their contents in a pH-dependent manner. The acetal cross-linker was also used to synthesize microgels with sizes between 1 and 10 mum, a range suitable for phagocytosis. The unique acid sensitivity of the acetal cross-linker should make it a useful synthetic intermediate in the design of acid-sensitive drug or gene delivery systems.     

Synthesis and characterization of poly(N‐(2‐mercaptoethyl) acrylamide) microgel for biomedical applications

N‐(2‐mercaptoethyl) acrylamide (MEAM) monomer was synthesized by acrylation of cysteamine and was cross‐linked with ethylene glycol dimethacrylate (EGDMA) via dispersion polymerization forming poly(N‐(2‐mercaptoethyl) acrylamide) (p(MEAM)) microgel. Then, the prepared microgels were tested for potential biomedical use, eg, antioxidant capacity and blood compatibility, cytotoxicity, apoptotic, and necrotic cell death; drug delivery properties were determined. Antioxidant studies of p(MEAM) microgels revealed a super antioxidant capability with total phenol content and trolox equivalent antioxidant capacity as 6.05 ± 1.15 mg/L gallic acid equivalency and 40.96 ± 2.40 mM trolox/g, respectively. Moreover, the blood compatibility of p(MEAM) microgels on fresh blood was resulted in lower than 1.0% hemolysis ratios for all the studied concentration range, and the blood clotting index was determined as 60.66% at 2.0 mg/mL at microgel concentration. The biocompatibility studies employing WST‐1 test on L929 fibroblast cells and DLD‐1 colon cancer cells have shown that p(MEAM) microgel was biocompatible up to 200 μg/mL concentration with the cell viability values of 84.54% and 86.15% on L929 fibroblast and DLD‐1 colon cancer cells, respectively. Using Captopril was used as model drug to test p(MEAM) microgel as drug delivery device for in vitro release studies at different pHs. Release profile of Captopril was found linear up to 5 hours with the released amounts of 9.81, 12.24, and 13.78 mg g^‐1microgel at the pH 1.5, 7.4, and 9.0, respectively.     

Synthesis and polymerizations of phosphonated‐bis(methacrylamide)s for dental applications

Novel phosphonate and phosphonic acid‐containing bis(methacrylamide)s were synthesized. The phosphonate‐containing monomers ( 1a and 1b ) were synthesized by amidation of 2‐(2‐chlorocarbonyl‐allyloxymethyl)‐acryloylchloride with diethyl 2‐aminoethylphosphonate and diethyl 1‐aminomethylphosphonate. The phosphonic acid‐containing monomers ( 2a and 2b ) were synthesized by hydrolysis of 1a and 1b with trimethylsilyl bromide (TMSBr). All monomers were liquids and dissolved in water and ethanol. Thermal homopolymerization of 1a and 1b in bulk and solution using 2,2′‐azobis(isobutyronitrile) (AIBN) at 80 °C gave crosslinked polymers indicating low cyclization tendencies of these monomers. They were also homopolymerized using photo‐DSC with 2,2′‐dimethoxy‐2‐phenyl acetophenone (DMPA) as photoinitator, and their maximum rates of polymerization were found to be higher than commercial monomers 2,2‐bis[4‐(2‐hydroxy‐3‐methacryloyloxy propyloxy) phenyl] propane (Bis‐GMA) and 2‐hydroxyethyl methacrylate (HEMA), indicating their potential as reactive diluents or crosslinkers in dental materials. In fact, copolymerization with monomer 1a resulted in improvements in photopolymerization kinetics of both Bis‐GMA and HEMA. The acidic nature of the aqueous solutions (pH of 2a : 1.42, 2b : 1.53), stability under aqueous conditions after 1 month of study at 37 °C, interaction of 2a with hydroxyapatite (HAP) as representative of both monomers, and copolymerizability of the same with HEMA make these monomers suitable as adhesive monomers in dental adhesives, although their low observed reactivities may present a drawback. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012     

A new strategy to prepare temperature-sensitive poly(<Emphasis Type="Italic">N</Emphasis>-isopropylacrylamide) microgels

In this study, a new method was developed to prepare temperature-sensitive poly(N-isopropylacrylamide) microgels by free radical precipitation polymerization using siloxane coupling agent as the new crosslinker. Ammonium persulfate acted as the initiator for the radical copolymerization as well as the catalyst for the hydrolysis/condensation of the siloxane groups. The particle diameter and polydispersity of the microgels were measured by photon correlation spectroscopy and the results display that the microgels are monodisperse. The microgels exhibit temperature sensitivity and the phase transition temperature is approximately 31 °C. Furthermore, the diameter of the microgels changes upon heating and cooling processes. These were observed to be reversible. The novel crosslinking method described herein is the condensation of siloxane groups, which is totally different from the traditional double-vinyl crosslinkers. This innovative approach offers an alternative path to prepare functional core–shell particles and inorganic/organic hybrid materials.     

Preparation and properties of thermo-sensitive organic/inorganic hybrid microgels

By utilizing the hydrolysis and condensation of the methoxysilyl groups, thermo-sensitive organic/inorganic hybrid poly[ N-isopropylacrylamide- co-3-(trimethoxysilyl)propylmethacrylate] [P(NIPAm- co-TMSPMA)] microgels were successfully prepared via two different methods without addition of any surfactant. First, the microgels were obtained by a two-step method; that is, the linear copolymer P(NIPAm- co-TMSPMA) was first synthesized by free radical copolymerization, and the aqueous solution of the copolymer was then heated above its low critical solution temperature (LCST) to give colloid particles, which were subsequently cross-linked via the hydrolysis and condensation of the methoxysilyl groups to form the microgels. Second, the microgels were also prepared via conventional surfactant-free emulsion polymerization (SFEP) of the monomers NIPAm and TMSPMA. TMSPMA can act as the cross-linkable monomer. No surfactant was involved in the preparation of the hybrid microgels. The obtained microgels were rather spherical and exhibited reversible thermo-sensitive behavior. The size, morphology, swellability, and phase transition behavior of the microgels were dependent on the initial copolymer or monomer concentration, preparation temperature, and the content of TMSPMA. The size of microgels obtained by SFEP was found to be more uniform than that by the two-step method. The hybrid microgels obtained by these two methods had more homogeneous microstructures than those prepared via conventional emulsion polymerization with chemical cross-linker N, N'-methylene-bisacrylamide.     

Synthesis and properties of water‐soluble azlactone copolymers

Preparation and study of a series of copolymers incorporating 2‐vinyl‐4,4‐dimethylazlactone (VDMA) is reported. The reactivity ratios for photo‐initiated free radical copolymerization of VDMA with methacrylic acid (MAA), acrylic acid (AA), acrylamide (AAm), dimethylacrylamide (DMAA), hydroxyethyl methacrylate (HEMA), methoxy poly(ethylene glycol) methacrylate (MPEG₃₀₀MA), and 2‐methacryloyloxyethyl phosphorylcholine (MPC), were determined by fitting comonomer conversion data obtained by in situ ¹H NMR to a terminal copolymerization equation. Semi‐batch photo‐copolymerizations were then used to synthesize the corresponding VDMA copolymers with constant composition. Their solubility and dissolution behavior, as well as their hydrolysis half‐lives under physiological conditions, were determined. P(VDMA‐co‐MAA) copolymers with 52 to 93 mol % VDMA showed decreasing initial solubility and increasing hydrolysis half‐lives with increasing VDMA content. VDMA copolymers with nonionic monomers AAm and DMAA were water soluble only at VDMA contents of 41 and 22 mol % or less, respectively, and showed longer hydrolysis half‐lives than comparable MAA copolymers. VDMA copolymers with HEMA and MPEG₃₀₀MA were found to crosslink during storage, so their hydrolysis half‐lives were not determined. VDMA copolymers with 18% zwitterionic MPC showed a much longer half‐life and superior initial solubility compared to analogous p(VDMA‐co‐MAA), identifying this copolymer as a promising candidate for macromolecular crosslinkers in, for example, aqueous layer‐by‐layer co‐depositions with polyamines. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012     

Amino acid‐derived Poly(L‐Lysine) (p(LL)) microgel as a versatile biomaterial: Hydrolytically degradable,drug carrying,chemically modifiable and antimicrobial material

Here, a microgel of poly(_L‐Lysine) (p(LL)) from an amino acid, _L‐Lysine, was synthesized by microemulsion technique using AOT as surfactant in gasoline. The prepared p(LL) microgel was shown to be hydrolytically degradable at pH values of 5.4, 7.4, and 9 in phosphate buffer solution (PBS). The protonated p(LL) microgel was loaded with model drugs such as naproxen and riboflavin and found to release about 80% of loaded naproxen in 180 minutes and 70% of loaded riboflavin in about 120 minutes suggesting the potential of p(LL) microgels to act as fast drug delivery vehicles. Furthermore, p(LL) microgels were chemically modified with 1‐bromoethane (BE), 1‐bromooctane (BO), and 1‐bromoethylamine (BEA) to render antimicrobial capabilities. It was found that protonated p(LL) microgels had 29 ± 1 mm inhibition zone diameter for Pseudomonas aeruginosa ATCC 10145. Furthermore, minimum inhibition concentration (MIC) and minimum bactericidal concentration (MBC) values for Staphylococcus aureus ATCC 6538 were also calculated as 1 and 2.5 mg/mL concentrations, respectively, for protonated p(LL) microgels.     

Inducing pH responsiveness via ultralow thiol content in polyacrylamide (micro)gels with labile crosslinks

Here we present the synthesis and characterization of pH responsive polyacrylamide microgels, synthesized via free radical polymerization of acrylamide and bis (acryloylcystamine) (BAC). The gels were made with ultralow amounts of thiol functional groups incorporated into the polymer. The resulting gel monoliths were mechanically chopped into microgel particles with size distributions ranging from 80 to 200 mum. The gels exhibit an interesting reversible pH-dependent rheological behavior which led to gelling of the colloidal suspension when the pH was increased, and a low-viscosity suspension was obtained when the pH was taken back to the original value. The viscosity of the colloidal system containing MBA crosslinked microgels remained insensitive to pH. This observation motivated further analysis; viscosity measurements of the highly viscous (gel-like) state of the BAC crosslinked microgel colloidal suspension were carried out to further understand the rheological behavior of the colloidal system. Electrophoretic mobility measurements as function of pH of the BAC and MBA crosslinked colloidal polyacrylamide microgel suspensions were performed. The swelling behavior of the microgels for both colloidal systems was also determined as function of pH using static light scattering. This swelling behavior was used to rationalize the observed rheological behavior. The work presented here demonstrates that free thiol groups present within a polymer gel matrix confer pH responsive behavior to the gel in solution. The viscosity of a BAC crosslinked microgel suspension was also measured under reducing conditions. The viscosity of the microgel suspension reduced with time, due to the breakage of the disulfide bonds in the crosslinkers.     

The dual temperature/pH-sensitive multiphase behavior of poly(N-isopropylacrylamide-co-acrylic acid) microgels for potential application in in situ gelling system

Poly(N-isopropylacrylamide-co-acrylic acid) microgels (PNA) may be an excellent formulation for in situ gelling system due to their high sensitivity and fast response rate. Four monodispersed PNA microgels with various contents of acrylic acid (AA) were synthesized by emulsion polymerization in this paper. Their hydrodynamic diameters decreased reversibly with both decreasing pH and increasing temperature. The dual temperature/pH-sensitivity was influenced by many factors such as AA content, cross-link density and ion strength. In addition, high concentration PNA dispersions underwent multiple phase transition according to different temperatures, pHs and concentrations, which were summarized in a 3D sol-gel phase diagram in this study. According to the sol-gel phase transition, 8% PNA-025 dispersion maintained a relatively low viscosity and favorable fluidity at pH 5.0 in the temperature range of 25-40°C, but it rapidly increased in viscosity at pH 7.4 and gelled at 37°C. This feature enabled the dual temperature/pH-sensitive microgels to overcome the troubles in syringing of temperature sensitive materials during the injection. Apart from this, PNA could form gel well in in vitro (e.g., medium and serum) and in in vivo with low cytotoxicity. Therefore, it is promising for PNA to be applied in the in situ gelling system.     

Novel copolymer networks via the combination of polyaddition and anionic polymerization

A two‐step synthetic route to novel copolymer networks, consisting of polymethacrylate and polyacetal components, was developed by combining the polyaddition and anionic polymerization techniques. The functional polymethacrylates containing hydroxyl or vinyloxyl side groups were used as crosslinkers. They were anionically synthesized as follows: the copolymer of 2‐hydroxyethyl methacrylate (HEMA) and methyl methacrylate (MMA) was prepared by the anionic copolymerization of 2‐(trimethylsiloxy)ethyl methacrylate and MMA, followed by hydrolysis. The copolymer poly(HEMA‐co‐MMA) thus obtained possessed a hydroxyl group in each of its HEMA units. Another kind of vinyloxyl‐containing (co)polymer was prepared by the anionic homopolymerization of 2‐(vinyloxy)ethyl methacrylate (VEMA) or its copolymerization with MMA. The resulting (co)polymer possessed reactive vinyloxyl side groups. The copolymer networks were obtained by reacting each of the above‐mentioned (co)polymers with a polyacetal prepared via the polyaddition between a divinyl ether and a diol. Three divinyl ethers (ethylene glycol divinyl ether, 1,4‐butanediol divinyl ether, and 1,6‐hexanediol divinyl ether) and three diols (ethylene glycol, 1,4‐butanediol, and 1,6‐hexanediol) were employed as monomers in the polyaddition step, and their combinations generated nine kinds of polyacetals. When a polyaddition reaction was terminated with a divinyl ether monomer, a polyacetal with two vinyloxyl end groups was obtained, which could further react with the hydroxyl groups of poly(HEMA‐co‐MMA) to generate a copolymer network. On the other hand, when a diol was used as terminator in the polyaddition, the resulting polyacetal possessed two hydroxyl end groups, which could react with the vinyloxyl groups of poly(VEMA) or poly(VEMA‐co‐MMA), to generate a copolymer network. All the copolymer networks exhibited degradation in the presence of acids. © 2000 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 39: 117–126, 2001     

Facile synthesis of thermo- and pH-responsive biodegradable microgels

A novel and facile strategy has been designed to prepare biodegradable microgels with thermo- and pH-responsive property. The microgels were synthesized by the crosslinking of N-isopropylacrylamide with vinyl groups functionalized poly(L-glutamic acid) (PGA). The resultant microgels exhibited pH-dependent phase transition behaviors in aqueous solutions and underwent abrupt lower critical solution temperature decrease when the pH was reduced below the pK _a of PGA. Dynamic light scattering measurement revealed that the microgels exhibited shrinkage as the temperature increased or the pH decreased.     

侧链含不同功能性羟基的温敏性N-异丙基丙烯酰胺共聚物微凝胶的制备及性能比较

选择含有活性羟基的亲水单体多缩乙二醇单甲基丙烯酸酯(PEGMA)、甲基丙烯酸羟乙酯(HEMA),分别和N-异丙基丙烯酰胺(NIPAM)交联共聚,制备了侧链含有功能性羟基、链长不同的温敏性微凝胶.研究发现,亲水单体HEMA和PEGMA的引入对微凝胶的去溶胀性能有不同的影响,PEGMA的引入使得微凝胶的体积相转变温度升高,微凝胶的去溶胀比随着PEGMA投料比的增加而降低.而HEMA的引入使得微凝胶的体积相转变温度降低;微凝胶的去溶胀比随着HEMA投料比的增加先是增加然后降低,当HEMA的投料比为8mol%时,去溶胀比达到最大.     

Hydrophobic cryogels for DNA adsorption: Effect of embedding of monosize microbeads into cryogel network on their adsorptive performances

As alternative hydrophobic adsorbent for DNA adsorption, supermacroporous cryogel disks were synthesized via free radical polymerization. In this study, we have prepared two kinds of cryogel disks: (i) poly(2‐hydroxyethyl methacrylate‐N‐methacryloyl‐l ‐tryptophan) [p(HEMA‐MATrp)] cryogel containing specific hydrophobic ligand MATrp; and (ii) monosize p(HEMA‐MATrp) particles synthesized via suspension polymerization embedded into p(HEMA) cryogel structure to obtain p(HEMA‐MATrp)/p(HEMA) composite cryogel disks. These cryogel disks containing hydrophobic functional group were characterized via swelling studies, Fourier transform infrared spectroscopy, elemental analysis, surface area measurements and scanning electron microscopy. DNA adsorption onto both p(HEMA‐MATrp) cryogel and p(HEMA‐MATrp)/p(HEMA) composite cryogels was investigated. Maximum adsorption of DNA on p(HEMA‐MATrp) cryogel was found to be 15 mg/g polymer. Otherwise, p(HEMA‐MATrp)/p(HEMA) composite cryogels significantly increased the DNA adsorption capacity to 38 mg/g polymer. Composite cryogels could be used repeatedly without significant loss on adsorption capacity after 10 repetitive adsorption–desorption cycles. Copyright © 2013 John Wiley & Sons, Ltd.     

New Biocompatible Microgels

Summary: Microgel particles have received an increasing interest in the biomedical field. Temperature-sensitive microgels gained particular interest due to their potential use as controlled drug delivery systems. With the objective to produce new thermoresponsive biocompatible microgels, the synthesis and characterization of two families of microgel particles obtained by using N-vinylcaprolactam (VCL) as main monomer and N,N′-methylenbisacrylamide (BA) or poly(ethylene glycol) diacrylate (PEGDA) as crosslinkers are described. Evidence of hydrolysis VCL during polymerization is also presented.     

不同交联剂对甲基丙烯酸-β-羟乙酯/E-51双甲基丙烯酸酯聚合物水凝胶性能的影响

以水溶性单体甲基丙烯酸-β-羟乙酯(HEMA)与大分子交联剂E-51双甲基丙烯酸酯(E-51-DMA)(质量比HEMA/E-51-DMA=90/10)为主要原料,分别引入了5种小分子交联剂:N,N′-亚甲基双丙烯酰胺(MBA)、二乙烯基苯(DVB)、双甲基丙烯酸乙二醇酯(EDMA)、1,1,1-三(丙烯酰氧甲基)丙烷(TAP)和2,2,2-三(丙烯酰氧甲基)乙醇(TAE),采用本体聚合方法合成了5个系列的聚合物水凝胶.研究了小分子交联剂的类型及用量对水凝胶溶胀性能、杨氏模量以及有效交联密度ve和聚合物-水相互作用参数χ的影响,并比较了不同交联剂的交联效率.结果表明,随着小分子交联剂用量的增大,水凝胶平衡含水量EWC逐渐降低,聚合物体积分数2逐渐增大,反映聚合物网络结构的有效交联密度ve以及热力学参数聚合物-水相互作用参数χ值也随之增大.通过理论交联密度和有效交联密度的线性拟合,得到所选用的5种小分子交联剂在E-51-DMA10/HEMA90水凝胶体系中的交联效率,其顺序为DVB>EDMA>TAE>MBA≈TAP.     

The effect of humic acid adsorption on pH-dependent surface charging and aggregation of magnetite nanoparticles

The pH-dependent adsorption of humic acid (HA) on magnetite and its effect on the surface charging and the aggregation of oxide particles were investigated. HA was extracted from brown coal. Synthetic magnetite was prepared by alkaline hydrolysis of iron(II) and iron(III) salts. The pH-dependent particle charge and aggregation, and coagulation kinetics at pH approximately 4 were measured by laser Doppler electrophoresis and dynamic light scattering. The charge of pure magnetite reverses from positive to negative at pH approximately 8, which may consider as isoelectric point (IEP). Near this pH, large aggregates form, while stable sols exist further from it. In the presence of increasing HA loading, the IEP shifts to lower pH, then at higher loading, magnetite becomes negatively charged even at low pHs, which indicate the neutralization and gradual recharging positive charges on surface. In acidic region, the trace HA amounts are adsorbed on magnetite surface as oppositely charged patches, systems become highly unstable due to heterocoagulation. Above the adsorption saturation, however, the nanoparticles are stabilized in a way of combined steric and electrostatic effects. The HA coated magnetite particles form stable colloidal dispersion, particle aggregation does not occur in a wide range of pH and salt tolerance is enhanced.     

Highly regenerable ionic liquid microgels as inherently metal‐free green catalyst for H2 generation

Polymeric ionic liquid (PIL) microgel of poly([2‐(methacryloyloxy)ethyl]trimethylammonium chloride) (p(MTMA)) was synthesized by using an inverse suspension polymerization technique. The anion‐exchanged PIL microgels via chloride replacement from p(MTMA) were prepared as p(MTMA)‐potassium thiocyanate (p(MTMA)‐KSCN), p(MTMA)‐sodium tetrafluoroborate (p(MTMA)‐NaBF₄), and p(MTMA)‐sodium dicyanamide (p(MTMA)‐NaN(CN)₂) microgels by treatment with corresponding salts of potassium thiocyanate (KSCN), sodium tetrafluoroborate NaBF₄, and sodium dicyanamide NaN(CN)₂ in aqueous media. The prepared microgels were found to be efficient metal‐free catalysts, and their catalytic activity in H₂ production from the methanolysis of NaBH₄ was investigated. Moreover, various parameters affecting H₂ production such as the effect of microgel size, the concentration of NaBH₄, the effect of the anion in the microgel, the reusability of the microgel, and temperature were investigated. The Ea value calculated for the methanolysis reaction of NaBH₄ catalyzed by p(MTMA) microgels was found as 24.1 ± 0.7 kJ mol⁻¹ ranging from −15 to 45°C, and this Ea value is lower than some Ea values for the same reaction. Interestingly, 10‐time successive use of p(MTMA) microgel as catalyst in NaBH4 methanolysis reduced its catalytic activity to 49%, whereas the anion‐exchanged forms of p(MTMA) microgel, p(MTMA)‐KSCN, p(MTMA)‐NaBF₄, and p(MTMA)‐NaN(CN)₂ only reduced their catalytic activity to 89, 86, and 79%, respectively, after 10 consecutive uses. Therefore, these anion‐exchanged microgel catalysts are highly efficient in comparison with virgin p(MTMA) microgels for regenerable H₂ generation from the methanolysis of NaBH₄.     

pH响应性P(MMA-co-MAA-co-HEMA)微凝胶的制备及其性能

利用预乳化乳液法制备了不同单体配比的聚(甲基丙烯酸甲酯-co-甲基丙烯酸-co-甲基丙烯酸羟乙酯)(P(MMA-co-MAA-co-HEMA))微凝胶分散液;采用透射电子显微镜、动态光散射仪研究了微凝胶的微观形态、粒径大小及其溶胀率;利用试管倒转法对微凝胶分散液的凝胶化相转变行为进行了研究,借助椎板流变仪考察了所形成胶态凝胶的储能模量与单体配比、微凝胶分散液浓度和温度的关系.结果表明,所制备的微凝胶的数均粒径为90 nm左右,当MMA与MAA的投料质量不变时,随着HEMA含量的增加,分散液凝胶化所需的临界最小浓度增大,临界最大pH值减小,胶态凝胶的储能模量增加.当保持单体MMA与HEMA的投料质量不变时,随着单体MAA投料质量的增多,微凝胶的数均粒径和溶胀率增大,胶态凝胶的储能模量先升高后降低;当MAA占单体总摩尔数的25%时,浓度为15 wt%的微凝胶分散液在扫描频率为100 rad/s时,胶态凝胶的储能模量最高可达2×104Pa.这类微凝胶分散液在组织工程支架材料方面有潜在的应用价值.     

Synthesis and properties of organic-inorganic hybrid P(NIPAM-<Emphasis Type="Italic">co</Emphasis>-AM-<Emphasis Type="Italic">co</Emphasis>-TMSPMA) microgels

Utilizing the hydrolysis and condensation of the methoxysilyl moieties, organic-inorganic hybrid poly(N-isopropylacrylamide-co-acrylamide-co-3-(trimethoxysilyl)propylmethacrylate) P(NIPAM-co-AM-co-TMSPMA) microgels were prepared via two different methods. The first method was that the microgels were post-fabricated from the crosslinkable linear P(NIPAM-co-AM-co-TMSPMA) terpolymer aqueous solutions above the lower critical solution temperature (LCST) of the terpolymer. For the second method, the microgels were directly synthesized by conventional surfactant free emulsion copolymerization of NIPAM, AM, and TMSPMA. The hydrodynamic diameter and stability of the resultant P(NIPAM-co-AM-co-TMSPMA) microgels strongly depend on the pH and temperature of the microgel aqueous solution. The hydrodynamic diameters of the microgels decreased with increasing the measuring temperature. The phase transition temperature of the microgels was found to be around 34°C, which was independent of the initial terpolymer concentration and shifted to lower temperature with increasing the preparation temperature. Increasing the initial amount of AM will enhance the instability of the microgels at high pH values. Moreover, the P(NIPAM-co-AM-co-TMSPMA) microgels obtained from the linear terpolymer had more homogeneous microstructures as compared with the corresponding NIPAM/AM/TMSPMA microgels prepared by one step emulsion copolymerization as revealed by light scattering measurements.     

Rational design of salmeterol xinafoate imprinted polymer through computational method: Functional monomer and crosslinker selection

A molecular imprinted polymer (MIP) was computationally designed and synthesized for the selective extraction of salmeterol xinafoate (SLX) from human serum. In this study, semi-empirical PM3 calculations were used to find a suitable functional monomer (FM), the ratio of template (T) to FM, and types of crosslinkers. MIPs were synthesized with 2-hydroxyethyl methacrylate (HEMA) with T:FM mol ratios of 1:6 and 1:4 and ethylene glycol dimethacrylate (EGDMA) or trimethylolpropane trimethacrylate (TRIM) as a crosslinker. On the basis of computational and experimental results, HEMA and TRIM in the mol ratio 1:6 of T-FM (MIP3) were found to be the best choices of FM and crosslinker, respectively. These polymers were then used as a selective sorbent to develop a molecularly imprinted solid-phase extraction procedure followed by high performance liquid chromatography with UV detection for the determination of SLX in serum. The extraction ability of MIP3 was excellent with a recovery of 92.17% ± 2.66% of SLX in spiked serum, and 91.15% ± 1.12% when SLX was spiked as a mixture with another analogous structure. By comparing the performance of the synthesized sorbent with a C-18 cartridge with a recovery of 79.11% ± 2.96%, it was determined that MIP had better performance over the latter. On the basis of these results, the imprinted receptor MIPs, especially MIP 3, can be applied for the direct extraction of SLX in clinical analysis.