甘草次酸(β)海藻酸钠-羧甲基壳聚糖复合凝胶珠的制备及体外释放

以海藻酸钠-羧甲基壳聚糖(ALG-CMC)为载体材料,甘草次酸(β)(GA)为模型药物,采用滴制法制备了ALG-CMC负载GA的复合凝胶珠。采用体视显微镜与扫描电镜(SEM)观察了凝胶珠的外观形貌,考察了凝胶珠的溶胀性能和体外释药行为,以及CaCl2浓度对凝胶珠的包封率和载药量的影响。结果表明,湿态凝胶珠形态规整、粒径分布均匀,平均粒径约2900μm,包封率最高达85.7%,载药量为18.0%;CaCl2浓度对包封率和载药量几乎无影响;在pH=1.2的HCl溶液中凝胶珠溶胀率小、累积释放率低;在pH=7.4的磷酸盐缓冲(PBS)溶液中凝胶珠溶胀率大、累积释放率高。滴制法制备ALG-CMC凝胶珠条件温和、不接触有机溶剂,凝胶珠具有pH敏感性且能有效载药。该体系有可能成为GA的给药载体材料。     

海藻酸钠-g-聚丙烯酰胺/氧化石墨烯复合水凝胶的制备及控释行为

以海藻酸、丙烯酰胺为单体,氧化石墨烯为原料制备了海藻酸钠-g-聚丙烯酰胺/氧化石墨烯(NaAlg-g-PAAm/GO)复合水凝胶,采用傅里叶变换红外光谱和扫描电镜对其结构和形貌进行了表征;当GO的质量分数从0.6%增至3.2%时,溶胀率从37%减至21%;阳离子对水凝胶的溶胀性的影响能力是Fe3+Ca2+K+;以5-氟尿嘧啶(5-FU)为抗癌药物模型,模拟胃腔和小肠的环境,研究了在pH=1.2和pH=7.4的缓冲溶液中复合水凝胶的控制释放行为,实验结果表明水凝胶在pH=7.4的缓冲溶液中的累积释放率明显高于在pH=1.2的溶液中的累积释放率,所以该类水凝胶有望成为靶向药物释放的载体。     

pH/盐双敏感型聚离子液体凝胶的制备及对环丙沙星的控制释放

以不同烷基侧链的N-乙烯基咪唑类离子液体为单体,设计合成了3种具有pH/盐双敏感性的交联网状孔洞结构的聚咪唑类离子液体凝胶(PC_nvimBr,n=2,4,6)。在微观结构、溶胀特性和刺激响应行为研究基础上,探讨了侧链微增长对聚离子液体凝胶结构与性能的调节控制,并根据凝胶的构效关系情况进行相应药物的体外控制释放研究,研究表明,PC_nvimBr凝胶具有良好的pH/盐刺激双响应性以及溶胀可逆性。在pH=7.4的弱碱性环境下,三种聚离子液体凝胶均具有较强的敏感性及溶胀可逆性,其中PC_2vimBr凝胶的pH响应性最为敏感,其平衡溶胀率高达1422.3%。同时,以NaCl盐溶液为模拟模型,相对而言,PC_2vimBr凝胶在弱碱性条件下具有良好的盐敏感性。此外,结合人体肠道呈弱碱性特点,以肠道杀菌药物环丙沙星(CIP)为载药模型,在pH=7.4时药物控制释放的体外模拟实验研究发现,PC_2vimBr凝胶10 h内的累积释放率为67.78%,是PC_4vimBr、PC_6vimBr凝胶的1.42和3.38倍,这与pH/盐刺激双响应性的研究结果一致。因此,烷基侧链微增长对凝胶结构具有较强的调控作用,pH/盐双敏感性的PC_2vimBr凝胶在肠道杀菌药物的控制释放具有潜在的应用价值。     

海藻酸钠-g-聚丙烯酰胺/氧化石墨烯复合水凝胶的制备及控释行为EI北大核心CSCD

以海藻酸、丙烯酰胺为单体,氧化石墨烯为原料制备了海藻酸钠-g-聚丙烯酰胺/氧化石墨烯(NaAlg-g-PAAm/GO)复合水凝胶,采用傅里叶变换红外光谱和扫描电镜对其结构和形貌进行了表征;当GO的质量分数从0.6%增至3.2%时,溶胀率从37%减至21%;阳离子对水凝胶的溶胀性的影响能力是Fe3+>Ca2+>K+;以5-氟尿嘧啶(5-FU)为抗癌药物模型,模拟胃腔和小肠的环境,研究了在pH=1.2和pH=7.4的缓冲溶液中复合水凝胶的控制释放行为,实验结果表明水凝胶在pH=7.4的缓冲溶液中的累积释放率明显高于在pH=1.2的溶液中的累积释放率,所以该类水凝胶有望成为靶向药物释放的载体。     

基于聚甲基丙烯酸的pH敏感靶向释药性能研究

以5-氨基水杨酸(5-ASA)为模型药物分子,pH敏感水凝胶聚甲基丙烯酸(PMAA)为载体,采用浸渍法实现了药物在载体上的负载,载药量约为23.3wt%。通过体外模拟释放实验,研究了该凝胶在不同pH值模拟胃液(pH=1.2)和模拟肠液(pH=7.5)中的释药行为。结果表明,药物在pH值较低的模拟胃液中释放的较慢,且最大累积释药率较低(～10.4%);在pH值较高的模拟肠液中释放的较快,最大累积释药率达～47.6%,并揭示了释药机理。因此,PMAA可实现药物5-ASA在模拟肠液中的靶向释放,在智能药物控释系统领域具有潜在的应用价值。     

苯乙烯/黏土协同作用对瓜尔胶复合高吸水凝胶性能影响

在瓜尔胶-g-聚丙烯酸钠/无机黏土(GG-g-PNaA/Clay)体系中引入疏水单体苯乙烯(St)参与接枝共聚,水溶液聚合法合成了瓜尔胶-g-聚(丙烯酸钠-co-苯乙烯)/无机黏土(GG-g-P(NaA-co-St)/Clay)复合凝胶。用红外光谱、紫外光谱和扫描电镜对复合凝胶进行了表征,考察了St与无机黏土的协同作用对凝胶三维网络和溶胀性能的影响。实验结果表明,当黏土的质量分数为10%时,随着St的加入,凝胶平衡溶胀倍率(Qeq)呈现先增大后降低趋势;当St质量分数为1.5%时,凝胶Qeq达到最大值。St与凹凸棒黏土、海泡石和蛭石协同作用,不仅使复合凝胶表面形貌粗糙度增加,孔洞增多,而且也使Qeq分别提高了48.9%、50.3%和37.5%。此复合凝胶在0.9%NaCl溶液和一定pH溶液中的Qeq也明显提高,并且经过5次溶胀-去溶胀平衡后,均表现出良好的盐和pH响应性。     

pH、离子强度敏感性壳聚糖水凝胶的合成及其对辅酶A的控制释放

以壳聚糖(CS),L-天冬氨酸(ASP)和戊二醛(GA)为原料,合成了具有pH、离子强度敏感性的壳聚糖水凝胶CS-GA-ASP.研究了交联剂含量、pH、离子强度对水凝胶溶胀率的影响和水凝胶对辅酶A的控制释放.结果表明,水凝胶在酸性溶液中,溶胀率最大,在中性溶液中溶胀率最小;水凝胶在不同pH或不同离子强度的溶液中交替放置时,表现出良好的溶胀-退胀可逆性;在室温下,pH=3.7、6.8、9的缓冲溶液中,辅酶A的累积释放率分别为78%、92%和87%,且在pH=6.8的缓冲溶液中,辅酶A释放速率最快,在pH=3.7的缓冲溶液中时,辅酶A释放速率最慢.     

含笼形POSS的PNIPAM温敏性水凝胶的溶胀及药物缓释行为

以八乙烯基低聚倍半硅氧烷(OVPS)为交联剂,通过溶液共聚制备了聚N-异丙基丙烯酰胺有机/无机杂化水凝胶(P(OVPS-co-NIPAM)),研究了其溶胀、消溶胀和再溶胀及药物缓释行为。结果表明,所有P(OVPS-co-NIPAM)杂化水凝胶的平衡溶胀率SR均随温度升高而降低。20℃,5-P(OVPS-co-NIPAM)杂化水凝胶在去离子水中的SR与常规水凝胶P(MBA-co-NIPAM)相同,但在生理盐水中的SR,前者明显大于后者。随着OVPS含量的增加,杂化水凝胶的SR、再溶胀和消溶胀速率均逐渐下降。5-P(OVPS-co-NIPAM)杂化水凝胶的载药率和累积释药率均高于常规水凝胶P(MBA-co-NIPAM)。此外,P(OVPS-co-NIPAM)杂化水凝胶的药物释放速率均高于常规水凝胶,而且20℃时随OVPS含量增加,释药加快。     

壳聚糖/果胶及其衍生物水凝胶的制备与在药物控制释放中的应用

以戊二醛为交联剂制备了壳聚糖/果胶(CS-PT)水凝胶和壳聚糖/辛基果胶水凝胶。研究了制备条件对两种水凝胶溶胀性能的影响。实验表明,交联剂含量、pH、离子强度对CS-PT和壳聚糖/辛基果胶水凝胶溶胀度的影响较大,且在酸性条件下的水凝胶的溶胀度远大于碱性条件下的溶胀度,包埋在水凝胶中的牛血清蛋白在pH=1.0条件下载药的水凝胶释药率大于pH=7.4和pH=9.18条件下的释药率。     

新型PMAA/MWCNT-COOH杂合水凝胶的合成与茶碱释放

通过甲基丙烯酸(MAA)的原位自由基交联聚合反应制备了一系列新型pH敏感的聚甲基丙烯酸/羧基化多壁碳纳米管(PMAA/MWCNT-COOH)杂合水凝胶.利用红外光谱分析仪(FT-IR)、环境扫描电镜(ESEM)、动态粘弹谱仪(MDA)等对杂合水凝胶的结构、形态和力学性能进行表征.结果表明,MWCNT-COOH的引入,使杂合水凝胶的溶胀速率明显高于纯PMAA水凝胶;在溶胀状态下的力学性能测试表明,水凝胶弹性、回复性能等达到了软组织材料的要求.掺杂不同含量的碳纳米管和改变不同pH环境会影响永凝胶的溶胀行为,改变网孔密度和孔径大小,决定在载、释药物过程中起到重要作用.以茶碱为模拟药物对凝胶载、释药物的研究发现,茶碱在肠道环境中释放速率较快,约8h就达到平衡;而在胃部环境中释放较慢,达到平衡需要时间较长.因此,PMAA/MWCNT-COOH杂合水凝胶有望成为一种潜在的控制药物释放型生物医学材料.     

pH-sensitive sodium alginate/calcined hydrotalcite hybrid beads for controlled release of diclofenac sodium

Objective: The aim of this study was to prepare pH-sensitive sodium alginate/calcined hydrotalcite (SA/CHT) hybrid bead with improved the burst release effect of the drug.

Materials and methods: A series of pH-sensitive SA/CHT hybrid beads were prepared by using Ca²⁺ cross-linking in the presence of diclofenac sodium (DS) and SA. The structure and drug loading of the beads were characterized by Fourier transform infrared spectroscopy and X-ray diffraction. The swelling and the drug release of the fabricated beads were investigated by the pH of test medium and CHT content.

Result: The formed positively charged hydrotalcite layers were adsorbed on the negatively charged SA polymer chains through electrostatic interaction and act as inorganic cross-linkers in the three-dimensional network. Compared to pure SA beads, the incorporation of CHT enhanced the drug encapsulation efficiency, improved the swelling behaviors and slowed the drug release from the hybrid beads.

Discussion and conclusions: The electrostatic interaction between hydrotalcite and SA has restricted the movability of the SA polymer chains, and then slowed down swelling and dissolution rates in aqueous solutions. The results provided a simple method to moderate drug release and matrix degradation of the SA beads.     

Evaluation of pH-Sensitivity and Drug Release Characteristics of (Polyacrylamide-Grafted-Xanthan)–Carboxymethyl Cellulose-Based pH-Sensitive Interpenetrating Network Hydrogel Beads

Novel pH-sensitive interpenetrating network hydrogel beads of polyacrylamide-grafted-xanthan (PAAm-g-XG) and sodium carboxymethyl cellulose (NaCMC) loaded with ketoprofen were prepared and evaluated for pH sensitivity and drug release characteristics. The pH-sensitive PAAm-g-XG copolymer was synthesized by free radical polymerization under the nitrogen atmosphere followed by alkaline hydrolysis. The grafting and alkaline hydrolysis reactions were confirmed by Fourier transform infrared spectroscopy. Differential scanning calorimetry and X-ray diffraction studies were carried out to know the crystalline nature of encapsulated drug. Scanning electron microscopic study revealed that the interpenetrating polymer network (IPN) beads possess porous matrix structure in alkaline pH whereas nonporous matrix structure was observed in acidic pH. The swelling of the beads and drug release was significantly increased when pH of the medium was changed from acidic to alkaline. The results of pulsatile swelling study indicated that the IPN beads changed their swelling behavior when pH of the external medium was altered. As pH of the medium was changed from 1.2 to 7.4, a considerable increase in swelling was observed for all the beads. However, swelling process was slower than the deswelling. At higher pH values, the carboxyl functional groups of hydrogels undergo ionization and the osmotic pressure inside the beads increases resulting in higher swelling. Drug release followed case II transport mechanism in acidic medium whereas anomalous/non-Fickian transport mechanism was observed in alkaline medium.     

Evaluation of pH-sensitivity and drug release characteristics of (polyacrylamide-grafted-xanthan)-carboxymethyl cellulose-based pH-sensitive interpenetrating network hydrogel beads

Novel pH-sensitive interpenetrating network hydrogel beads of polyacrylamide-grafted-xanthan (PAAm-g-XG) and sodium carboxymethyl cellulose (NaCMC) loaded with ketoprofen were prepared and evaluated for pH sensitivity and drug release characteristics. The pH-sensitive PAAm-g-XG copolymer was synthesized by free radical polymerization under the nitrogen atmosphere followed by alkaline hydrolysis. The grafting and alkaline hydrolysis reactions were confirmed by Fourier transform infrared spectroscopy. Differential scanning calorimetry and X-ray diffraction studies were carried out to know the crystalline nature of encapsulated drug. Scanning electron microscopic study revealed that the interpenetrating polymer network (IPN) beads possess porous matrix structure in alkaline pH whereas nonporous matrix structure was observed in acidic pH. The swelling of the beads and drug release was significantly increased when pH of the medium was changed from acidic to alkaline. The results of pulsatile swelling study indicated that the IPN beads changed their swelling behavior when pH of the external medium was altered. As pH of the medium was changed from 1.2 to 7.4, a considerable increase in swelling was observed for all the beads. However, swelling process was slower than the deswelling. At higher pH values, the carboxyl functional groups of hydrogels undergo ionization and the osmotic pressure inside the beads increases resulting in higher swelling. Drug release followed case II transport mechanism in acidic medium whereas anomalous/non-Fickian transport mechanism was observed in alkaline medium.     

Preparation and characterization of magnetic alginate-chitosan hydrogel beads loaded matrine

The aim of this study was to use alginate-chitosan (Alg-CS) hydrogel beads for developing an oral water-soluble drug delivery system, occupying pH-sensitive property and superparamagnetic. Matrine as a model drug was loaded in Alg-CS hydrogel beads to study the release character of the delivery system. The amount of matrine released from the beads was relatively low in pH 2.5 over 8?h (34.90%), but nearly all of the initial drug content was released in simulated intestinal fluid (SIF, pH 6.8) within 8?h. The results demonstrated that Alg-CS hydrogel beads possess unique pH-dependent swelling behaviors. In addition, the magnetic beads were characterized by Fourier transform infrared spectroscopy, scanning electron microscope, X-ray diffractometry and vibrating-sample magnetometry. Magnetometer measurements data suggested that Alg-CS beads also had superparamagnetic property as well as fast magnetic response. It can be expected that the beads can deliver and release encapsulated anticancer agent at the tumor by the weak magnetic field, and hence could be potential candidates as an orally administered drug delivery system.     

Preparation and characterization of magnetic alginate-chitosan hydrogel beads loaded matrine

The aim of this study was to use alginate-chitosan (Alg-CS) hydrogel beads for developing an oral water-soluble drug delivery system, occupying pH-sensitive property and superparamagnetic. Matrine as a model drug was loaded in Alg-CS hydrogel beads to study the release character of the delivery system. The amount of matrine released from the beads was relatively low in pH 2.5 over 8?h (34.90%), but nearly all of the initial drug content was released in simulated intestinal fluid (SIF, pH 6.8) within 8?h. The results demonstrated that Alg-CS hydrogel beads possess unique pH-dependent swelling behaviors. In addition, the magnetic beads were characterized by Fourier transform infrared spectroscopy, scanning electron microscope, X-ray diffractometry and vibrating-sample magnetometry. Magnetometer measurements data suggested that Alg-CS beads also had superparamagnetic property as well as fast magnetic response. It can be expected that the beads can deliver and release encapsulated anticancer agent at the tumor by the weak magnetic field, and hence could be potential candidates as an orally administered drug delivery system.     

海藻酸钠与羟乙基茯苓多糖复合凝胶球的制备及性能

为了提高海藻酸钠凝胶球的溶胀率和溶胀时间,将羟乙基茯苓多糖(HEP)引入海藻酸钠(ALG)/Ca2+交联的凝胶体系中,形成复合凝胶球,并研究其在模拟胃肠液中的溶胀行为。同时采用红外光谱与扫描电镜对该复合凝胶球的结构及形态进行了研究。结果发现该HEP/ALG复合凝胶球具有显著pH敏感性,即在酸性条件下,溶胀缓慢,但是在中性及碱性条件下,溶胀率大大提高。而且,与单一的海藻酸钠凝胶球相比,其溶胀时间延长了近1个小时,溶胀率可达到20左右。     

Biodegradable IPN hydrogel beads of pectin and grafted alginate for controlled delivery of diclofenac sodium

A novel diclofenac sodium (DS) loaded interpenetrating polymer network (IPN) beads of pectin and hydrolyzed polyacrylamide-graft-sodium alginate (PAAm-g-SA) was developed through ionotropic gelation and covalent cross-linking. The graft copolymer was synthesized by free radical polymerization under the nitrogen atmosphere followed by alkaline hydrolysis. The grafting, alkaline hydrolysis, and characterization of beads were confirmed by Fourier transforms infrared spectroscopy. The crystalline structure of drug after encapsulation into IPN beads were evaluated by differential scanning colorimetry and X-ray diffraction analyses. DS encapsulation was up to 96.45 %. The effect of hydrolyzed graft copolymer/pectin ratios and glutaraldehyde concentration on drug release in acidic and phosphate buffer solutions were investigated. The release of drug was significantly increased with increase of pH. The release of drug depends on the extent of cross-linking. The results indicated that IPN beads of hydrolyzed PAAm-g-SA and pectin could be used for sustained release of DS.     

Study of formulation variables on properties of drug-gellan beads by factorial design

The aim of the present study was to obtain cross-linked calcium-gellan beads containing diclofenac sodium as model drug, using full 3(3) factorial design. Drug quantity, pH of cross-linking solution, and speed of agitation were selected as variables for factorial design. The resultant beads were evaluated by scanning electron microscopy (SEM), percent yield, entrapment efficiency, micromeritic properties, swelling and drug release studies. The drug-loaded beads were spherical with size range of 0.85-1.8 mm. Percent yield and entrapment efficiency of various batches were in the range of 86.48-98.28% w/w and 72.52-92.74% w/w, respectively. Calcium-gellan beads containing diclofenac sodium showed pH-dependent swelling and drug release properties. Swelling and drug release were significantly higher in pH 7.4 phosphate buffer than 0.1N HCl. The swelling ratio for beads was up to 22 and 3 for phosphate buffer and 0.1N HCl, respectively. Cumulative diclofenac sodium release from calcium-gellan beads was 12-35% in 0.1N HCl within 2 h, whereas complete drug release was observed within 3-4 h in pH 7.4 phosphate buffer.     

Poly (vinyl alcohol) hydrogels for pH dependent colon targeted drug delivery

Oral drug administration is convenient with pH dependent drug delivery system since the drug has to pass through different pH environments in gastro intestinal (GI) tract. The pH dependent swelling/shrinking behavior of hydrogel drug carrier controls the drug release without affecting the function of drug. pH dependent hydrogels of poly (vinyl alcohol) (PVA) were prepared by cross linking with maleic acid (MA). The hydrogels were characterized by attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy, DSC, porosimetry, SEM, TEM, biocompatibility study and by measuring their swelling behavior in water, simulated gastric fluid (SGF) and intestinal fluid (SIF). Swelling of the hydrogels was found to be highest in SIF (pH: 7.5) and lowest in SGF (pH: 1.2) resembling that required in colon targeted drug delivery systems. Since the swelling behavior of the gel is pH dependent, these hydrogels were studied for colon targeted drug delivery in an in-vitro set-up resembling the condition of GI tract. The ratio of PVA and MA in the hydrogel was varied to study the effect on the drug diffusion rate. For drug delivery study, vitamin B12 and salicylic acid were used as model drugs. The hydrogel, loaded with model drugs vitamin B12 and salicylic acid also demonstrated colon specific drug release with a relatively higher drug release in SIF (pH: 7.5) than that in SGF (pH: 1.2).     

Poly (vinyl alcohol) hydrogels for pH dependent colon targeted drug delivery

Oral drug administration is convenient with pH dependent drug delivery system since the drug has to pass through different pH environments in gastro intestinal (GI) tract. The pH dependent swelling/shrinking behavior of hydrogel drug carrier controls the drug release without affecting the function of drug. pH dependent hydrogels of poly (vinyl alcohol) (PVA) were prepared by cross linking with maleic acid (MA). The hydrogels were characterized by attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy, DSC, porosimetry, SEM, TEM, biocompatibility study and by measuring their swelling behavior in water, simulated gastric fluid (SGF) and intestinal fluid (SIF). Swelling of the hydrogels was found to be highest in SIF (pH: 7.5) and lowest in SGF (pH: 1.2) resembling that required in colon targeted drug delivery systems. Since the swelling behavior of the gel is pH dependent, these hydrogels were studied for colon targeted drug delivery in an in-vitro set-up resembling the condition of GI tract. The ratio of PVA and MA in the hydrogel was varied to study the effect on the drug diffusion rate. For drug delivery study, vitamin B₁₂ and salicylic acid were used as model drugs. The hydrogel, loaded with model drugs vitamin B₁₂ and salicylic acid also demonstrated colon specific drug release with a relatively higher drug release in SIF (pH: 7.5) than that in SGF (pH: 1.2).