一种新型聚天冬氨酸水凝胶的制备及其药物缓释性能研究

介绍了一种新型羟化聚天冬氨酸-乙基纤维素(PASP-EC)互穿网络水凝胶的制备,研究了交联剂用量、乙醇胺用量及乙基纤维素(EC)用量对水凝胶溶胀性能的影响;同时,进行了水凝胶的pH敏感性测试,并以5-Fu为药物模型,研究其在肠液中(pH=7.4)的药物控释性能。实验结果表明,当己二胺、乙醇胺、EC的用量分别是聚琥珀酰亚胺(PSI)用量的3%、20%、30%时,水凝胶的溶胀性能最佳,达到290倍;且随着乙醇胺用量的增加,水凝胶在50%乙醇中的溶胀性能提高。pH敏感实验表明,羟化PASP-EC水凝胶具有pH敏感性。羟化PASP-EC水凝胶对5-Fu具有缓释效果,随着EC用量增加,缓释效果越明显。     

Preparation a novel pH‐sensitive blend hydrogel based on polyaspartic acid and ethylcellulose for controlled release of naproxen sodium

Hydrogels based on pH‐sensitive polymers are of great interest as potential biomaterials for the controlled delivery of drug molecules. In this study, a novel, pH‐sensitive hydrogel was synthesized by poly(aspartic acid) (PASP) crosslinked with 1,6‐hexanediamine and reinforced with ethylcellulose (EC). The loading and release characteristics of naproxen sodium (NS) were studied. The PASP–EC blend hydrogels had pH‐sensitive characteristics and were strongly dependent on the pH value. The release kinetics for NS from the PASP–EC blend hydrogels and PASP hydrogel were evaluated in simulated gastric fluid (pH = 1.05) and simulated intestinal fluid (pH = 6.8) at 37°C. The results showed that the drug‐loaded hydrogels were resistant to simulated gastric fluid, and hence, they could be useful for oral drug delivery. Compared with the PASP hydrogel, the PASP–EC blend hydrogels showed a lower release rate of NS in the same pH conditions. It was evident that the presence of hydrophobic groups (EC) retarded the release of NS and led to sustained release. The kinetics of NS release from the drug‐loaded hydrogels conformed to the Korsmeyer–Peppas model. The release exponent of the model was 0.7291, which indicated multiple drug release. The PASP–EC blend hydrogels were biodegradable and pH sensitive; there would be a wide range of applications for them in controlled drug‐delivery systems. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009     

聚天冬氨酸水凝胶合成及其应用于药物控释的研究进展

聚天冬氨酸是一种新型的聚合氨基酸材料,具有很好的生物相容性、生物降解性。本文综述了聚天冬氨酸及其衍生物水凝胶的研究现状,介绍了化学交联、光交联、γ射线交联3种交联方法合成的聚天冬氨酸及其衍生物水凝胶,以及近年来聚天冬氨酸基凝胶对大分子蛋白药物、小分子抗炎性药物、抗癌和基因药物控释的研究进展,并对该凝胶在药物控释领域的发展方向进行了预测。     

聚天冬氨酸凝胶的制备及生物降解性

以丙三醇三缩水甘油醚为交联剂制备聚天冬氨酸凝胶,考察了凝胶的热性能和黏弹性,并采用平板培养和液体培养法考察了凝胶的生物降解性。结果表明:丙三醇三缩水甘油醚交联凝胶具有良好的吸水保水性,且耐热性和黏弹性更优,平板试验证明凝胶也具有良好的生物降解性,液体培养法证明交联剂的种类和用量对凝胶的降解有较大影响,交联度均为60%的凝胶,交联剂为丙三醇三缩水甘油醚时第9天降解率为49.3%,较交联剂为乙二醇二缩水甘油醚制备的凝胶低9.2%,说明在相同交联度下丙三醇三缩水甘油醚形成的网络结构更致密;交联剂均为丙三醇三缩水甘油醚时,交联度为40%的第9天降解率为59.8%,较交联度为60%的凝胶提高了17.5%,交联度增加,降解速率降低。     

改性聚天冬氨酸复合水凝胶的制备及性能

以聚琥珀酰亚胺（PSI）、丙烯酸（AA）和丙烯酰胺（AM）为原料,KH550和KH570为联合交联剂,采用水溶液聚合法合成了聚天冬氨酸/聚（丙烯酸-丙烯酰胺）复合水凝胶［KPAsp/P（AA-AM）］;探讨了交联剂用量、原料配比对KPAsp/P（AA-AM）复合水凝胶溶胀性能的影响;采用FTIR和TG对水凝胶进行了表征。结果表明当v（KH550）∶v（KH570）=1∶1和n（PSI）∶n（AA）∶n（AM）=1∶3∶1时,所合成的复合水凝胶溶胀性能最佳,溶胀度达到395。通过吸水动力学研究表明,共聚链的引入改变了水凝胶的吸水行为。研究了复合水凝胶对阿莫西林的控释性能,结果表明,复合水凝胶的载药量可达29.98mg/g;在37℃、pH=1.8的NaCl溶液中,负载了阿莫西林的复合水凝胶在2h对药物的释放率达到57%,24h左右达到85%。     

聚天冬氨酸衍生物的合成及阻垢性能研究

绿色阻垢剂已成为当前研究的热点.采用磷酸作催化剂,以L-天冬氨酸热聚合,再与三乙醇胺化合的方法合成了一种不含磷的环保型阻垢剂聚天冬氨酸衍生物.实验研究发现,聚天冬氨酸衍生物的阻垢性能优于聚天冬氨酸.在使用质量浓度为8 mg/L时,该阻垢剂对碳酸钙垢的阻垢率就已超过85%,10 mg/L时对硫酸钙垢的阻垢率超过90%;试剂的阻垢性能受循环冷却水的温度和pH影响不大,对温度不超过80℃、pH不高于9.5条件下运行的循环冷却水系统有很好的阻垢作用.     

Preparation of a novel pH-sensitive hydrogel based on acrylic acid and polyhedral oligomeric silsesquioxane for controlled drug release of theophylline

Hydrogels based on pH-sensitive polymers are of great interest as potential biomaterials for the controlled delivery of drug molecules. In this study, a novel pH-sensitive copolymer hydrogel based on acrylic acid (AA) monomer by free-radical solution polymerization were synthesized with organic–inorganic cross-linking agent of octavinyl polyhedral oligomeric silsesquioxane (OVPOSS). And its properties were compared with conventional hydrogels using N,N′-methylenebisacrylamide (MBA) as cross-linking agent. The copolymers were characterized by Fourier transform infrared spectra and differential scanning calorimetry. The morphology after swelling was presented by scanning electron microscopy. Swelling behaviors in different pH and potential applications in controlled drug delivery of the hydrogels were also examined. The results showed that both hydrogels were pH sensitive. However, as the addition of OVPOSS limited the movement of the molecular chain segment, the swelling ratio and the drug-release rate of theophylline in SGF decreased obviously when using OVPOSS as cross-linking agent, comparing with P(MBA-co-AA) hydrogels. The results in this study suggested that P(OVPOSS-co-AA) could serve as potential candidate for theophylline drug delivery.     

pH-sensitive IPN hydrogel based on poly (aspartic acid) and poly (vinyl alcohol) for controlled release

Various pH-sensitive sequential interpenetrating polymer network (IPN) hydrogels were prepared by introducing poly (vinyl alcohol) (PVA) hydrogel into Poly (aspartic acid) (PASP) hydrogel by freeze-thawing treatment to obtain a novel drug delivery system to the intestine. The structure and the morphologies of the prepared hydrogels were studied by Fourier Transform Infrared Spectroscopy (FTIR) and scanning electron microscopy (SEM). The thermal behavior and crystallinity of the hydrogels were characterized by differential scanning calorimetry (DSC) and X-ray diffraction (XRD). Their pH-sensitive properties moreover were studied and the results revealed that both PASP hydrogel and IPN hydrogels exhibited excellent pH-sensitivity. Furthermore, the controlled drug release properties of the hydrogels were also evaluated and results indicated that by increasing the PVA fraction in the IPN hydrogel, the release of Naproxen sodium was improved. These results show that the IPN hydrogels could be a suitable carrier for site-specific drug delivery in the intestine.     

Dextrin crosslinked with poly(lactic acid): A novel hydrogel for controlled drug release application

A new class of biodegradable crosslinked hydrogel, consisting of hydrophobic polylactic acid (PLA) and hydrophilic dextrin in presence of crosslinker N,N‐methylene bisacrylamide (MBA) has been synthesized by free‐radical polymerization technique using potassium persulfate (KPS) as initiator. By variation of crosslinker concentration, a series of hydrogels have been prepared and the optimized grade has been selected on the basis of higher crosslinking efficiency as well as lower equilibrium swelling characteristics, XRD analysis. The hydrogels have been characterized by FTIR spectra, ¹³C‐NMR spectra, CHN analysis, SEM analysis, swelling characteristics, and toxicity study. In vitro release study of model drugs (ciprofloxacin and ornidazole) from hydrogel matrix has been performed in various buffer solutions at 37°C. The drug release kinetics and mechanism have been studied using zero order, first‐order kinetic models, Korsemeyar–Peppas model, Higuchi model, Hixson–Crowell model, and nonlinear Kopcha model. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 40039.     

多支化聚天冬氨酸衍生物的合成及其阻垢性能研究

先以顺酐和氨水等为原料合成聚天冬氨酸(PASP),再以PASP和赖氨酸为原料进行接枝反应得到改性聚天冬氨酸衍生物(Lys-PASP)。实验结果表明,与聚天冬氨酸相比,在聚天冬氨酸与赖氨酸质量比为10∶1,改性时间2 h,改性温度120℃条件下得到的改性产品Lys-PASP不仅对碳酸钙具有更好的阻垢性能,而且对碳钢表面也有更好的缓蚀效果,并对氧化铁也具有很好的分散效果;Lys-PASP的加入,不仅改变了碳酸钙的晶型,而且大大降低了碳酸钙晶体的完整程度和有序度,达到了阻止碳酸钙垢形成的目的,起到了阻垢缓蚀的效果。     

Novel degradable polyphosphazene hydrogel beads for drug controlled release

Novel water‐soluble polyphosphazene containing carboxylatophenamino groups (PCPAP) was synthesized by the substitution reaction of ethyl p‐amino benzonate with poly(dichlorophosphazene), followed by alkali hydrolysis. Characterizations by IR, ¹H‐NMR, differential scanning calorimetry, and elemental analysis indicated that the reaction brought about an almost complete introduction of carboxylatophenamino to the polymer side chain. Calcium‐crosslinked PCPAP hydrogel beads were accomplished with an extremely mild method. The erosion experiments were conducted in vitro in various pH environments. The erosion duration of the beads at pH 7.4 and 37°C was effectively extended by an increase in the concentration of the PCPAP or CaCl₂ solution during the preparation process. Moreover, the bead erosion was sensitive to the pH. The sample dissolved 39.4% in a pH 8.0 buffer within 34 days but only 5.3% in a pH 5.0 buffer. Furthermore, PCPAP underwent degradation into macromolecular segments through the breaking of the backbone, and this could prevent accumulation in the body. These properties of PCPAP may be useful for controlled drug delivery, including intestine‐specific oral delivery systems. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 87: 986–992, 2003     

聚天冬氨酸衍生物的合成及阻垢性能

利用天冬氨酸热缩聚产物聚琥珀酰亚胺（PSI）和天冬氨酸（ASP）合成了一种聚天冬氨酸衍生物。研究了聚琥珀酰亚胺与天冬氨酸不同比例时的接枝率,考察了聚天冬氨酸衍生物的阻垢性能。利用红外光谱对聚天冬氨酸衍生物的结构进行了表征,利用扫描电子显微镜对CaCO₃晶形进行了观察和分析。实验结果表明：当PSI与ASP的摩尔比为1∶1.8时,产物的接枝率最高,达到了66.45％,其阻垢效果也最好。当Ca²⁺质量浓度为400 mg•L^-1、HCO^-₃质量浓度为800 mg•L^-1、聚天冬氨酸衍生物用量为6 mg•L^-1时,阻垢率达到100％。聚天冬氨酸衍生物对CaCO₃有晶格扭曲和分散作用。     

A rechargeable drug delivery system based on pNIPAM hydrogel for the local release of curcumin

This study was designed to develop a drug delivery system based on poly(N-isopropylacrylamide) (pNIPAM) hydrogel and a suitable solvent to enhance solubility and local release of curcumin. pNIPAM hydrogel was synthesized by radical polymerization. The chemical, mechanical and physical properties and biocompatibility of pNIPAM hydrogel were investigated as an implantable and rechargeable drug reservoir. Curcumin was loaded within pNIPAM hydrogel during swelling by using two different solvents; methanol, an organic solvent, and low molecular weight polyethylene glycol (PEG200), a polymeric solvent. The results of drug solubility showed that using PEG200 can increase curcumin solubility more than commonly used organic solvents such as methanol. Also, the release profile of drug-loaded hydrogels demonstrated that PEG200 has a superior effect on the cumulative amount of released curcumin (33.163 ± 0.319 μg/ml) compared to methanol (8.765 ± 0.544 μg/ml) during 1 week. Based on our results, curcumin-loaded hydrogels did not show any cytotoxicity, and pNIPAM/PEG combination represented an antibacterial effect within 12 hours. Accordingly, it can be concluded that pNIPAM hydrogel in combination with low molecular weight PEG200 could be used as an efficient drug delivery system to preserve and provide sustained release of curcumin as a hydrophobic drug.     

溶液电导率法对绿色水处理剂聚天冬氨酸的阻垢性能的研究

采用电导法研究聚天冬氨酸(PASP)对碳酸钙垢的阻垢性能,考察了PASP用量、温度、溶液中钙离子浓度、pH等因素的影响。结果表明,PASP的质量浓度从10 mg/L上升到40 mg/L,CaCO3相对过饱和度增加迅速,浓度升高到40 mg/L以后,相对过饱和度增加态势趋于稳定,其相对过饱和度为4.7;温度越高,PASP的相对过饱和度越高,适用于高温环境;钙离子浓度对相对过饱和度影响不大,PASP可适用于高钙离子含量的溶液中。     

Genipin cross-linked chitosan hydrogel for the controlled release of tetracycline with controlled release property,lower cytotoxicity,and long-term bioactivity

To realize the controlled release property, lower cytotoxicity, and long-term bioactivity of tetracycline, the chitosan hydrogel had been prepared using genipin as the cross-linker and the tetracycline was in situ encapsulated. The formation process and strength of hydrogel were studied by rheological analysis, and the microtopography was observed by scanning electron microscope. It was found that the amount of genipin could modulate the physical property of the hydrogel. For in vitro release and antibacterial assays, the hydrogel could controllably release tetracycline and keep its bioactivity for a long time. The tetracycline-loaded chitosan hydrogel showed good antibacterial effect even under alkaline environment, which displayed better stability compared with free tetracycline. Moreover, the tetracycline-loaded chitosan hydrogel exhibited lower cytotoxicity than did tetracycline alone, suggesting that this tetracycline-loaded chitosan hydrogel could be a more useful dosage form than separate doses of tetracycline. The novel aspects of this study include the cytotoxicity study and the in vitro and in vivo assays, which might be useful for other researchers in this field.

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Graphical abstract To realize the controlled release property, lower cytotoxicity, and long-term bioactivity of tetracycline, genipin cross-linked chitosan hydrogel was used as the carrier of tetracycline. The hydrogel could controllably release tetracycline with bioactivity. The hydrogel showed good antibacterial effect even under alkaline environment. The hydrogel exhibited lower cytotoxicity than did tetracycline alone.

     

Preparation and characterization of polyurethane based on dimer acid for environment-friendly controlled release fertilizers

ABSTRACT

The paper presents a new controlled release fertilizer coated by dimer acid-based polyurethane (PU). The structure and property of the sample were characterized. Results indicated that the polyether polyol modified PU (MPU) coating reduced water absorption rate by 72.1% after 29 d, and increased the cross-linking density by 23%, and decreased the coating porosity by 26%, Moreover, MPUFs and PUFs both exhibited excellent nutrient controlled release abilities, especially the MPUF possessed longer nitrogen release longevity (118 d,131%) compared with PUF (51 d). Thus, the high-performance MPUFs with environmentally friendly and excellent controlled release could be widely applied to agricultural fields.     

Amphiphilic chitosan/acrylic acid/thiourea based semi-interpenetrating hydrogel: Solvothermal synthesis and evaluation for controlled release of organophosphate pesticide,triazophos

The current study reports the solvothermal synthesis of amphiphilic chitosan-based semi-interpenetrating (CAT-SIPH) hydrogel for controlled release of an organophosphate pesticide, triazophos. CAT-SIPH is prepared from natural backbone polymer chitosan (CS) and monomer, acrylic acid (AA) employing initiator (K₂S₂O₈), and cross-linker, thiourea (CSN₂H₄) using solvothermal technique under 7 Psi pressure in an autoclave. The polymerization reaction variables like reaction time, the volume of solvent, concentration of initiator, cross-linker, and monomer are optimized to get the best product yield in terms of percentage grafting. The optimized conditions for solvothermal polymerization reaction carried out for 60 min are solvent volume (10 ml), concentrations of acrylic acid (0.2 mol/L), K₂S₂O₈ (0.45 × 10⁻²mol/L) and thiourea (1.75 × 10⁻⁴ mol/L). The swelling behavior of CAT-SIPH hydrogel synthesized under optimized conditions is studied in the terms of swelling ratio. CAT-SIPH is characterized by Fourier transform infrared spectra (FT-IR), ^IHNMR, thermal analysis (TA), Zeta potential, and scanning electron microscopy (SEM). The potential of cross-linked hydrogel CAT-SIPH for controlled release of an organophosphate pesticide, Triazophos on to sandy loam soil is assessed. The experimental investigations proved that synthesized hydrogel can be effectively employed as a pesticide carrier for controlled release on to loamy soil as the maximum release (53%) is observed even after 25 days at pH 6 and value get lowered under acidic and basic conditions. The present investigation demonstrated the potential of chitosan-based CAT-SIPH hydrogel as a pH-responsive release vehicle for agrochemicals onto the soil matrix and offers a potential solution for the prevention of surface and groundwater contamination.     

机械活化淀粉制备水凝胶及其尿素的控释性

以机械活化60 min的木薯淀粉、氢氧化钾部分中和的丙烯酸和丙烯酰胺为原料,合成农用淀粉基离子/非离子型复合高吸水树脂(SCSA),采用FT-IR和SEM对样品的官能团和表面形貌进行表征。以SCSA在5.0 mol·L^-1的尿素溶液中平衡溶胀后所得的水凝胶(SCH)为尿素在水溶液中的释放材料,考察合成工艺条件和释放环境对尿素释放过程的影响。结果表明,尿素从SCH中的释放过程符合Fickian扩散机理;SCH的溶胀率越大,尿素的释放速率越慢;释放温度越高,尿素的释放越快。在丙烯酸和丙烯酰胺质量比为3:3,交联剂N,N'-亚甲基双丙烯酰胺溶液用量为1.0 ml(浓度为0.02 mol·L^-1)的条件下制备的SCH对尿素的释放活化能为17.28 kJ·mol^-1。     

热缩聚天冬氨酸合成方法研究

以L-天冬氨酸为原料,采用热缩聚合、液相聚合和改性聚合三种方法合成了热缩聚天冬氨酸.采用红外光谱与X光衍射技术研究了反应物预处理前后的特征,对聚合工艺条件进行了优化和对比,对合成产物进行了结构表征,并对产品阻垢性能进行了对比分析.结果表明,热缩聚合、液相聚合与改性聚合工艺反应温度分别为210、180、180℃;反应时间分别为3.0、1.3、1.0 h;催化剂最佳化学计量数分别为0.12、0.18、0.08.热缩聚合与液相聚合产品的阻垢性能相当,改性聚合产品的阻垢率约提高6.8%.说明改性聚合是一种较先进的聚天冬氨酸的合成方法.     

Thermoresponsive/low‐fouling Zwitterionic hydrogel for controlled drug release

A controlled/ living free‐radical polymerization technique was introduced to prepared a homogeneous poly(N‐isopropylacrylamide)‐g‐poly(sulfobetaine methacrylate) hydrogel (RG) possessing a highly porous architecture via two steps. Compared to a poly(N‐isopropylacrylamide)‐co‐poly(sulfobetaine methacrylate) hydrogel (CG) prepared by conventional radical polymerization, RG exhibited a much faster shrinking rate (it lost over 72% of the water in 15 min) in response to the temperature changes. The release behaviors of tetracycline hydrochloride (TCHC) of the hydrogels indicated the TCHC release from the RG could be prolonged to 48 h at 37°C; this was much longer than that for CG (5 h at 37°C). Bovine serum albumin (BSA) was chosen as the model protein to examine the low‐fouling properties of the RG. The BSA adsorption data showed that improved antifouling properties could be achieved by the RG at both 25 and 37°C. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 39816.