Adsorption of bovine serum albumin to acrylamide–itaconic acid hydrogels

In this study, acrylamide–itaconic acid hydrogels containing different amounts of itaconic acid prepared by irradiating with γ radiation are discussed. They have been used in experiments of swelling, diffusion and bovine serum albumin (BSA) adsorption. Maximum and minimum swellings were observed with water (1520%) and BSA (890%), respectively. Diffusion of water, NaCl and BSA within hydrogels were found to be non-Fickian in character. In the experiments of BSA adsorption, type III adsorption was found. The hydrogel prepared with 60 mg itaconic acid and irradiated at 2.00 kGy was found to be the best adsorption system for BSA. The adsorption capacity of acrylamide–itaconic acid hydrogel was found to exceed that of acrylamide hydrogel by more than 80–100%.     

An enhanced immobilization of BSA biomolecule on anionic hydrogels: swelling and adsorption modeling

The three-dimensional structure of hydrogels plays a leading role in several areas of applications. The hydrogels are more and more used as systems of immobilized and controlled release of biomolecules in biotechnology and bio-pharmacy industries. To improve protein adsorption capacity in poly(acrylamide) hydrogels, maleic acid co-monomer was included into the reaction mixture during hydrogel synthesis. So, hydrogels of poly(acrylamide) and its copolymers with diprotic maleic acid were prepared by copolymerization and chemical crosslinking with N,N′-methylene bis-acrylamide. Swelling behavior in distilled water, in physiological saline and in bovine serum albumin (BSA) solutions was studied. Influence of initial BSA concentration on hydrogel swelling and BSA adsorption was investigated. The high amount of maleic acid present in the hydrogels has a significant effect on the swelling behavior and BSA adsorption. Results showed that the pH sensitivity of hydrogels resulted in the high amount of adsorbed BSA. The adsorption isotherms were described by Langmuir and Freundlich models. The thermodynamic parameter (ΔG _ads ⁰ ) was determined for all obtained hydrogels. We demonstrated the favorable character and reversibility of the BSA adsorption process.     

Superabsorbent hydrogels based on cellulose for smart swelling and controllable delivery

Novel superabsorbent hydrogels were prepared successfully from carboxymethylcellulose sodium (CMC) and cellulose in the NaOH/urea aqueous system by using epichlorohydrin (ECH) as cross-linker. The structure and morphology of the hydrogels were characterized by FT-IR spectroscope, thermogravimetric analysis and scanning electron microscope. The results revealed that the CMC contributed to the enhanced size of pore, whereas cellulose as a strong backbone in the hydrogel to support it for keeping its appearance. Their equilibrium swelling ratio in distilled water and different physiological fluids were evaluated, indicating the maximum swelling ratio in water reached an exciting level of 1000 as the hydrogels still keeping a steady appearance. Moreover, the hydrogels exhibited smart swelling and shrinking in NaCl or CaCl₂ aqueous solution, as well as the release behavior of bovine serum albumin (BSA) that could be controlled by changing CMC content. The cellulose-based hydrogels are promising for the applications in the biomaterials area.     

APPLICATION OF NONIONIC TEMPERATURE SENSITIVE HYDROGEL FOR CONCENTRATION OF PROTEIN AQUEOUS SOLUTION

Six different N-alkyl substituted acrylarnide nonionic hydrogels were prepared and their swelling characteristics were measured. Poly N-isopropyl acrylamide (PNIPA) and poly N-n-propyl-acrylamide (PNNPA) temperature sensitive hydrogels were chosen as the nonionic temperature sensitive hydrogels for concentration of very dilute aqueous protein solution. The separation properties of PNIPA and PNNPA hydr0gels with different network dimensions were studied and the modification of the hydrogels was surveyed in order to decrease their surface adsorption of protein molecules. The experimental results of the concentration of BSA (Bovin serum albumin) dilute aqueous solution by hydroxylpropyl methacrylate (HPMA) copolymerized PNIPA hydrogel were given. The value and the limitation of concentration of dilute aqueous protein solution by this method was evaluated.     

A new specific metal ion chelated‐poly(N‐vinylimidazole) gel sorbents for albumin adsorption‐desorption

Poly(N‐vinylimidazole) (PVIm) hydrogels were prepared by γ‐irradiating binary mixtures of N‐vinylimidazole‐water in a ⁶⁰Co‐γ source having 4.5 kGy/h dose rate. These affinity gels having different swelling ratio of Cu(II)‐chelated, Co(II)‐chelated and plain PVIm in acetate buffer were used in the albumin adsorption studies. Bovine serum albumin (BSA) adsorption on these gels from aqueous solutions containing different amounts of BSA at different pH adjusted with acetate and phosphate buffer was investigated in batch reactors. The adsorption capacities of BSA on/in the gels were decreased dramatically by increasing the ionic strength (I) adjusting with NaCl. BSA adsorption capacities of the metal ion‐chelated gels were higher than the plain PVIm gel even if the swelling ratio of the metal ion‐chelated gels was very low comparing to the PVIm gel. The rigidity of the metal ion‐chelated gel is very high and it can be used for the column applications. More than 95% of BSA were desorbed in 3 h in the desorption medium containing KSCN for PVIm gel and EDTA for metal ion‐chelated gels. These results indicate that PVIm and metal ion‐chelated PVIm gels are very efficient to remove BSA and the different metal ion‐chelated PVIm gels show different affinity for BSA or biomolecules.     

瓜胶/聚丙烯酸互穿聚合物网络水凝胶对模型药物的负载与控制释放

考察了以牛乳清蛋白(BSA)为模型药物,通过相平衡分配法制备载药瓜胶(GG)/聚丙烯酸(PAA)互穿聚合物网络(IPN)水凝胶的工艺条件.借助紫外可见光谱仪研究了载药水凝胶在结肠酶存在下的控制释放行为.结果表明:载药容量(CM)随瓜胶、丙烯酸用量的增加而下降,半IPN水凝胶的Cm较全IPN的略大;结肠酶能明显提高半IPN与全IPN中的BSA释放速率,且提高幅度随GG含量的增加而加快,GG/PAA IPN水凝胶具有结肠定位降解的特性,有望成为靶向结肠给药的理想载体材料.     

Synthesis,characterization, and evaluation of enzymatically degradable poly(N‐isopropylacrylamide‐co‐acrylic acid) hydrogels for colon‐specific drug delivery

The enzymatically degradable poly(N‐isopropylacrylamide‐co‐acrylic acid) hydrogels were prepared using 4,4^′‐bis(methacryloylamino)azobenzene (BMAAB) as the crosslinker. It was found that the incorporated N‐isopropylacrylamide (NIPAAm) monomer did not change the enzymatic degradation of hydrogel, but remarkably enhanced the loading of protein drug. The hydrogels exhibited a phase transition temperature between 4°C (refrigerator temperature) and 37°C (human body temperature). Bovine serum albumin (BSA) as a model drug was loaded into the hydrogels by soaking the gels in a pH 7.4 buffer solution at 4°C, where the hydrogel was in a swollen status. The high swelling of hydrogels at 4°C enhanced the loading of BSA (loading capability, ca. 144.5 mg BSA/g gel). The drug was released gradually in the pH 7.4 buffer solution at 37°C, where the hydrogel was in a shrunken state. In contrast, the enzymatic degradation of hydrogels resulted in complete release of BSA in pH 7.4 buffer solution containing the cecal suspension at 37°C (cumulative release: ca. 100 mg BSA/g gel after 4 days). Copyright © 2008 John Wiley & Sons, Ltd.     

In vitro release modulation and conformational stabilization of a model protein using swellable polyamidoamine nanosponges of β-cyclodextrin

New swellable cyclodextrin-based poly(amidoamine) nanosponges, named PAA-NS10 and PAA-NS11, were synthesized by crosslinking β-cyclodextrin with either 2,2-bisacrylamidoacetic acid or with polyamidoamine segments deriving from 2,2-bisacrylamidoacetic acid and 2-methylpiperazine, respectively. Water uptake studies showed a tremendous swelling capacity of both nanosponges, forming hydrogels. Time dependent swelling experiments in various aqueous media showed that the nanosponge hydrogels were stable over a period of at least 72 h maintaining their integrity. Thermal analysis showed that the two nanosponges were stable up to 250 and 300 °C, respectively. Both PAA-NS10 and PAA-NS11 were converted to aqueous nanosuspensions using the High Pressure Homogenization technique. Bovine serum albumin (BSA) was used as model protein to study the encapsulating capacity of these new β-cyclodextrin-based PAA-nanosponges. High protein complexation capacity was observed, as confirmed by UV spectroscopy. BSA encapsulation efficiency was greater than 90% on w/w basis for both nanosponges. In vitro BSA release studies were carried out showing a prolonged release of albumin from the two swollen BSA loaded β-CD PAA-NS over a period of 24 h.     

New semi-interpenetrating network hydrogels: synthesis, characterization and properties

Amphiphilic hydrogels composed of aliphatic polyesters and poly(ethylene glycol) have potential applications in drug delivery, tissue engineering and other biomedical devices due to their advantageous biological properties, biocompatibility and biodegradability. However, they also exhibit some shortcomings in terms of their reactivity, swelling and mechanical properties. To address these limitations, new semi-interpenetrating network (semi-IPN) hydrogels based on poly(ethylene glycol)-co-poly(epsilon-caprolactone) (PEG-PCL) diacrylate macromer and hydroxypropyl guar gum (HPGG) were prepared by a low intensity ultraviolet (UV) light irradiation method, and characterized by FT-IR, DSC and WAXD analysis. Their properties were evaluated by investigating the swelling kinetics, dynamic mechanical rheology and the release behavior for bovine serum albumin (BSA). It was found that the introduction of the semi-IPN structure and HPGG decreased the crystallinity of PEG segments in the hydrogel, and improved the swelling and mechanical properties of the hydrogel, as well as lowered the release percentage of BSA from the hydrogel. Such hydrogel materials may have more advantages as a potentially interesting platform for the design of medical devices.The elastic modulus (G') and viscous modulus (G') as a function of frequency for various hydrogel samples.     

γ-irradiated chitosan-polyvinyl pyrrolidone hydrogels as pH-sensitive protein delivery system

The effects of pH of the buffer solution and the composition of the hydrogel system on the bovine serum albumin (BSA) adsorption capacity of chitosan (CS)–polyvinyl pyrrolidone (PVP) (CSPVP) hydrogels and release of BSA were investigated. Poly-electrolyte CSPVP hydrogels with different compositions were prepared by irradiating CS/PVP/water mixtures with γ-rays at ambient temperature. The adsorption capacity of hydrogels was found to increase from 0 to 350 mg BSA/g dry gel, by changing external stimuli and hydrogel composition. The adsorption of BSA within CSPVP hydrogels increased with increase in CS content in the hydrogels. When the irradiation doses of hydrogel increased, the adsorption of BSA decreased. The maximum adsorption of BSA was observed at pH 5. A significant amount of the adsorbed BSA (up to 95%) was eluted in the phosphate medium containing 0.1 M NaCl at pH 7.4.     

A novel pH‐ and thermo‐sensitive PVP/CMC semi‐IPN hydrogel: Swelling,phase behavior,and drug release study

Poly(N‐vinyl‐pyrrolidone) (PVP) hydrogel has been considered as a very interesting and promising thermosensitive material. The most vital shortcoming of PVP hydrogel as thermosensitive material is that it does not exhibit thermosensitivity under usual conditions. In this work, semi‐interpenetrating polymer network (semi‐IPN) hydrogels based on PVP and carboxymethylcellulose (CMC) were prepared. The volume phase transition temperature (VPTT) of the hydrogels was determined by swelling behavior and differential scanning calorimetry (DSC). The results showed that the VPTT was significantly dependent on CMC content and the pH of the swelling medium. The amount of CMC in the semi‐IPN hydrogels was 0.050, 0.075, and 0.100 g, the VPTT in buffer solution of pH 1.2 was 29.9 °C, 27.5 °C and 24.5 °C, respectively. In addition, the VPTT occurred in buffer solution of pH 1.2, but did not appear in alkaline medium. Bovine serum albumin (BSA) as a model drug was loaded and the in vitro release studies were carried out in different buffer solutions and at different temperatures. The results of this study suggest that PVP/CMC semi‐IPN hydrogels could serve as potential candidates for protein drug delivery in the intestine. © 2010 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 48: 1749–1756, 2010     

P(AA-DAC)两性聚电解质水凝胶的合成及性质

以丙烯酸(AA)和丙烯酰氧乙基三甲基氯化铵(DAC)为单体, 采用水溶液聚合法制备了P(AA-DAC)聚电解质水凝胶. 采用红外光谱和核磁共振等方法对其结构进行了表征. 研究了不同组成比的聚电解质水凝胶在去离子水、不同pH值溶液以及不同离子强度盐溶液中的溶胀行为. 研究结果表明, 摩尔比为1∶1的聚电解质水凝胶表现出典型的两性聚电解质凝胶的溶胀行为. 离子强度对其溶胀行为有着显著影响, 在溶液离子强度较高时, 凝胶网络的溶胀主要受溶剂向凝胶内部扩散所控制, 满足Fick型扩散规律n≤0.5, 随着溶液离子强度的增加, 凝胶网络平衡含水量增加, 扩散系数增大.     

Novel poly(N‐isopropylacrylamide)/clay/poly(acrylamide) IPN hydrogels with the response rate and drug release controlled by clay content

Novel interpenetrating network (IPN) hydrogels (PNIPAAm/clay/PAAm hydrogels) based on poly(N‐isopropylacrylamide) (PNIPAAm) crosslinked by inorganic clay and poly(acrylamide) (PAAm) crosslinked by organic crosslinker were prepared in situ by ultraviolet (UV) irradiation polymerization. The effects of clay content on temperature dependence of equilibrium swelling ratio, deswelling behavior, thermal behavior, and the interior morphology of resultant IPN hydrogels were investigated with the help of Fourier transform infrared spectroscopy, differential scanning calorimeter (DSC), scanning electron microscope (SEM). Study on temperature dependence of equilibrium swelling ratio showed that all IPN hydrogels exhibited temperature‐sensitivity. DSC further revealed that the temperature‐sensitivity was weakened with increasing amount of clay. Study on deswelling behavior revealed that IPN hydrogels had much faster response rate when comparing with PNIPAAm/clay hydrogels, and the response rate of IPN hydrogels could be controlled by clay content. SEM revealed that there existed difference in the interior morphology of IPN hydrogels between 20 [below lower critical solution temperature (LCST)] and 50 °C (above LCST), and this difference would become obvious with a decrease in clay content. For the standpoint of applications, oscillating swelling/deswelling behavior was investigated to determine whether properties of IPN hydrogels would be stable for potential applications. Bovine serum albumin (BSA) was used as model drug for in vitro experiment, the release data suggested that the controlled drug release could be achieved by modulating clay content. © 2008 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 47: 96–106, 2009     

可生物降解的pH敏感水凝胶的合成及其溶胀性能研究

采用明胶和聚乙烯醇为原料,制备了戊二醛交联、明胶／聚乙烯醇配比不同的水凝胶,并用FTIR和SEM对产物进行了表征。研究了凝胶的溶胀动力学,结果表明,原料配比对各种凝胶的溶胀速率影响不大,而对平衡溶胀比与原料配比有关,室温下凝胶的平衡溶胀比在300％～500％之间。pH敏感性研究表明,几种凝胶均表现出明显的pH响应性,当溶胀介质的pH值在明胶等电点附近时,水凝胶的溶胀比达到最小值,凝胶的溶胀-消溶胀动力学曲线呈“W”形,即该凝胶具有形状记忆功能。     

Metal ion promoted hydrogels for bovine serum albumin adsorption: Cu(II) and Co(II) chelated poly[(N-vinylimidazole)-maleic acid

Poly[(N-vinylimidazole)-maleic acid] (poly(VIm-MA)), copolymeric hydrogels were prepared by gamma-irradiating ternary mixtures of N-vinylimidazole-maleic acid-water in a (60)Co-gamma source. Cu(II) and Co(II) ions were chelated within the gels at pH=5.0. The maximum adsorption capacity of the gels were 3.71 mmol/g dry gel for Cu(II) and 1.25 mmol/g dry gel for Co(II) at pH=5.0. The swelling ratios of the gels were 1200% for poly(VIm-MA), 60 and 45% for Cu(II) and Co(II)-chelated poly(VIm-MA) gels at pH=5.0 in acetate buffer solution. These affinity gels with different swelling ratios for plain poly(VIm-MA), Cu(II)-, and Co(II)-chelated poly(VIm-MA), in acetate and phosphate buffers were used in the bovine serum albumin (BSA) adsorption/desorption studies in batch reactor. The maximum BSA adsorption capacities of the gels were 0.38 g/g dry gel for plain, 0.88 g/g dry gel for Cu(II)-chelated poly(VIm-MA) and 1.05 g/g dry gel for Co(II)-chelated poly(VIm-MA) gels. Adsorption capacity of BSA by the gels was reduced dramatically by increasing the ionic strength adjusted with NaCl. More than 95% of BSA were desorbed in 10 h in desorption medium containing 0.1M of EDTA for metal ion-chelated gels at pH=4.7.     

pH快速响应PNIPAAm-co-PAAc水凝胶的制备及溶胀动力学

pH快速响应PNIPAAm-co-PAAc水凝胶的制备及溶胀动力学;N-异丙基丙烯酰胺;pH敏感性;溶胀历史     

Macroporous Poly(Acrylamide) Hydrogels: Swelling and Shrinking Behaviors

Macroporous poly(acrylamide) hydrogels have been synthesized by using poly(ethylene glycol) (PEG) with three different molecular weights as the pore‐forming agent. Scanning electron microscope graphs reveal that the macroporous network structure of the hydrogels can be adjusted by applying different molecular weights of PEG during the polymerization reaction. The swelling ratios of the PEG‐modified hydrogels were much higher than those for the same type of hydrogel prepared via conventional method. However, the swelling/deswelling ratios of the PEG‐modified hydrogels were affected slightly by the change in the amount of the PEG. Scanning electron microscopy experiments, together with swelling ratio studies, reveal that the PEG‐modified hydrogels are characterized by an open structure with more pores and higher swelling ratio, but lower mechanical strength, compared the conventional hydrogel. PAAm has potential applications in controlled release of macromolecular active agents.     

Synthesis and Properties of Poly(AAm‐KMA‐MA) Hydrogels

In this investigation, poly(acrylamide‐co‐potassium methacrylate‐co‐maleic acid) hydrogels, poly(AAm‐KMA‐MA) were synthesized by redox copolymerization in aqueous solution. The effect of reaction parameters, such as concentration of maleic acid, crosslinking agent, initiator and activator, on the swelling behavior was investigated in detail. The swelling/diffusion characteristics were also evaluated for 1,4‐butanediol diacrylate (BDDA) and 1,2‐ethyleneglycol dimethacrylate (EGDMA) crosslinked hydrogels having different amounts of maleic acid. The results indicate that the water diffusion of hydrogels was of a non‐Fickian type. The hydrogels were characterized by IR spectroscopy and thermogravimetric analysis (TGA). Their surface characteristics were observed by using scanning electron microscopy (SEM). Furthermore, their swelling phenomena in different pH and salt solutions and simulated biological fluids was also studied.     

Chitosan‐Based Thermo/pH Double Sensitive Hydrogel for Controlled Drug Delivery

A series of thermo/pH sensitive N‐succinyl hydroxybutyl chitosan (NSHBC) hydrogels with different substitution degrees of succinyl are prepared for drug delivery. Rheology analysis shows that the gelation temperature of NSHBC hydrogels is 3.8 °C higher than that of hydroxybutyl chitosan (HBC) hydrogels. A model drug bovine serum albumin (BSA) is successfully loaded and released. NSHBC hydrogels show excellent pH sensitivity drug release behaviors. After incubation for 24 h, 93.7% of BSA is released from NSHBC hydrogels in phosphate buffer saline (PBS) (pH 7.4), which is significantly greater than that of 24.6% at pH 3.0. In contrast, the release rate of BSA from HBC is about 70.0% at pH 3.0 and 7.4. Thus, these novel hydrogels have the prominent merits of high adaptability to soluble drugs and pH sensitivity triggered release, indicating that NSHBC hydrogels have promising applications in oral drug delivery.     

Studies on syntheses and dynamic swelling of pH-sensitive macroporous poly(N-isopropylacrylamide-co-acrylic acid) hydrogels

A series of macroporous poly(N-isopropylacrylamide-co-acrylic acid) (PNIPAm-AA) hydrogels with different composition were synthesized by free-radical copolymerization in the presence of silica particles as a pore generating agent. The equilibrium swelling ratio, half swelling time and dynamic swelling kinetics of the copolymers previously soaked in different acidic buffer solutions were investigated at pH 7 at 25°C. Experimental results revealed that the swelling rate of the macroporous hydrogels was greatly increased compared to conventional hydrogels due to existence of the macroporous structures. It was found that the swelling history of previously putting in acidic solutions copolymers had strong influence on their dynamic swelling kinetics especially for the samples ranging in composition between 30 and 70 mol % of NIPAAm, whereas the swelling history had little influence on the equilibrium swelling ratio of copolymers. The swelling pattern exhibits sigmoid swelling curves. This is explained by an autocatalytic mechanism. The hydrogen bonding dissociation plays an important role in the dynamic swelling behavior.