形状记忆型水凝胶的制备及其在药物控制释放中的应用

以戊二醛为交联剂,制备了pH敏感性明胶-果胶水凝胶(GT-PT)和明胶-辛基果胶水凝胶(GT-OPT),研究了交联剂用量、温度、pH值对凝胶溶胀性能的影响及溶胀-消溶胀性能。结果表明,当温度在30～60℃时,凝胶的溶胀率随温度的升高而增大;且具有明显的pH敏感性,碱性条件下的溶胀率大于酸性条件下的溶胀率;不同pH值条件下,明胶-果胶水凝胶具有"形状记忆"功能。包埋在水凝胶中的牛血清蛋白在pH=1.0时的释药率大于pH=7.8和pH=9.18时的释药率。此类水凝胶有望用于蛋白质的pH值及温度控制释放。     

透明质酸水凝胶的制备与评价

透明质酸(HA)被广泛地用于生物医药领域。以1-乙基-3-(3-二甲基氨丙基)-碳化二亚胺/N-羟基丁二酰亚胺(EDC/NHS)催化HA与己二酸二酰肼(ADH)反应,制备化学交联的HA水凝胶。通过扫描电镜和红外光谱来测定HA与HA水凝胶的结构,测量HA水凝胶在模拟胃肠液中的溶胀率,并以牛血清白蛋白(BSA)为模型药物,初步探讨了HA水凝胶体系的释药行为。实验结果显示:HA水凝胶由酰胺键生成三维网络结构且网络孔径较大,具有较好的吸水性能。该水凝胶制备过程简单,反应迅速,条件温和,属酸敏突释释药体系。     

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。     

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。     

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。     

PVA/P(AA-AM)复合水凝胶的制备及性能

采用水溶液聚合方法合成了不同组成的丙烯酸-丙烯酰胺共聚物(P(AA-AM))。将聚乙烯醇(PVA)与所合成的P(AA-AM)共混,以戊二醛为交联剂,制备出了不同结构的PVA/P(AA-AM)复合水凝胶。采用扫描电镜观察了凝胶形貌,研究了复合水凝胶的结构与性能关系。结果表明,复合水凝胶溶胀性能与所用交联剂加量有关,复合水凝胶的溶胀度随着交联剂加量增加先增大后减小,在交联剂加量为0.5%时水凝胶溶胀度达到最大值。复合凝胶中的聚合物组成对溶胀度影响显著,随着P(AA-AM)含量提高,水凝胶的溶胀度逐渐增大。适当结构的复合水凝胶具有pH敏感性,敏感程度随着凝胶中P(AA-AM)含量的增加而增强。     

不同条件对PVA/CS复合水凝胶溶胀性能的影响

以聚乙烯醇(PVA)、壳聚糖(CS)为原料,戊二醛为交联剂,制备出PVA/CS复合水凝胶载体材料,改变PVA/CS的质量配比、交联剂含量、pH值和温度,考察了不同条件下对复合水凝胶溶胀性能的影响.结果表明,当PVA/CS质量比为3:1、交联剂体积分数为4%时所合成凝胶的溶胀性能较好;随着温度的升高,溶胀度不断减小;凝胶在酸性条件的溶胀性能远远优于碱性条件的溶胀性能.     

分步合成羧甲基纤维素/聚丙烯酸甲酯pH敏感互穿网络水凝胶及其表征

以羧甲基纤维素(CMC)、聚丙烯酸甲酯(PMA)为互穿物,N,N'-亚甲基双丙烯酰胺(MBA)为交联剂,过硫酸钾(KPS)为引发剂,采用互穿网络(IPN)聚合分步合成法在乙醇的水溶液中合成出具有互穿网络结构的水凝胶。通过红外光谱、扫描电镜、X射线衍射和热重分析等表征了聚合物的互穿网络结构。pH溶胀实验结果表明,该水凝胶具有比较明显的pH敏感性,当pH在8.0左右,复合水凝胶的溶胀率达到了最大值,且随着CMC/PMA复合水凝胶中2种组分比例的不同,溶胀率有明显的差异。     

pH敏感性壳聚糖/聚乙烯醇水凝胶的制备及其性能研究

制备了pH敏感性壳聚糖/聚乙烯醇(CS-PVA)水凝胶,研究了该水凝胶在室温下不同pH值介质中的溶胀比。发现在酸性溶液中,凝胶的溶胀比远大于在碱性溶液中的溶胀比,且其在不同pH值溶液中具有可逆溶胀-收缩行为,对药物氟哌酸具有缓释效果。     

纳米羟基磷灰石/聚乙烯醇复合水凝胶的溶胀性

采用溶液共混合成法制备了纳米羟基磷灰石/聚乙烯醇(n-HA/PVA)复合水凝胶材料,研究了n-HA含量、冷冻循环次数与复合水凝胶含水率、溶胀比和溶解率之间的关系.结果表明水凝胶含水率、溶胀比和溶解率受冷冻-融化循环次数和n-HA含量的影响.随着n-HA的含量增加,含水率、溶胀比和溶解率逐渐减少.随着冷冻-融化循环次数的增加,含水率和溶解率逐渐降低而溶胀比逐渐增大.     

内盐凝胶的制备及对烟酰胺的控释

以甲基丙烯酸二甲基氨基乙酯(DMAE-MA)、衣康酸(IA)、亚甲基双丙基酰胺(BIS)和过硫酸钾(KPS)为原料在室温下制备内盐凝胶。研究了原料配方对凝胶形成的影响、内盐凝胶的吸水动力学及溶胀机制、凝胶的pH值敏感性以及对烟酰胺的负载与负载凝胶在不同pH值介质中的释放行为,并用红外光谱对凝胶结构进行了表征。结果表明,n(IA)/n(DMAEMA)>1后将降低单体的转化率,不利于凝胶的形成;内盐凝胶不具有高吸水性,其吸水溶胀机制符合Fickian扩散;在pH值为12的缓冲溶液中溶胀率比在pH值为3的缓冲溶液中高;凝胶对烟酰胺的负载率可以超过200%。在25℃下,烟酰胺在pH值为3的介质中释放比在pH值为12的介质中释放快。     

A covalently crosslinked polysaccharide hydrogel for potential applications in drug delivery and tissue engineering

The development of non-cytotoxic hydrogels that can allow for the controlled release of molecules has important clinical and therapeutic applications. In this paper, we developed a series of in situ hydrogels by combining N,O-carboxymethyl chitosan and oxidized alginate without additional crosslinking agents. The rheological properties of these hydrogels as well as their gelling time, swelling ratio, and in vitro degradation behavior were investigated. We observed that although gelation was rapid at physiological temperature, it was even faster in the presence of higher oxidization degree of alginate. In vitro cytotoxicity study showed that the developed hydrogels were not cytotoxic after 24?h of culturing with NIH-3T3 cells. Additionally, bovine serum albumin was released from the hydrogels initially by diffusion at early stages followed by a degradation-dependent mechanism at later stages. In conclusion, the developed hydrogel might have potential application in the drug delivery system and tissue engineering.     

pH-sensitive hydrogels based on semi-interpenetrating network (semi-IPN) of chitosan and polyvinyl pyrrolidone for clarithromycin release

The aim of this study was to develop a pH-sensitive chitosan/polyvinyl pyrrolidone (PVP) based controlled drug release system for clarithromycin. The hydrogels were synthesized by cross-linking chitosan and PVP blend with glutaraldehyde to form a semi-interpenetrating polymer network (semi-IPN). These semi-IPNs were studied for their content uniformity, swelling index (SI), mucoadhesion, wettability, in vitro release and their release kinetics. The hydrogels showed more than 97% content of clarithromycin. These hydrogels showed high swelling and mucoadhesion under acidic conditions. The swelling may be due to the protonation of a primary amino group on chitosan. In acidic condition, chitosan would be ionized, and adhesion could have occurred between the positively charged chitosan and the negatively charged mucus. In the alkaline condition, less swelling and mucoadhesion was noticed. In vitro release study revealed that formulation containing chitosan (2% w/v) and PVP (4% w/v) in the ratio of 21:4 showed complete drug release after 12 h. Release profile showed that all the formulations followed non-Fickian diffusion mechanism. The cross-linking and compatibility of clarithromycin in the formulation was studied by Fourier transform infrared (FTIR) spectroscopic analysis, differential scanning calorimetry (DSC) and powder X-ray diffraction (p-XRD) study, which confirmed proper formation of semi-IPN and stability of clarithromycin in the formulations. The surface morphology of semi-IPN was studied before and after dissolution in simulated gastric fluid (SGF, pH 1.2) which revealed pores formation in membrane after dissolution. The results of study suggest that semi-IPNs of chitosan/PVP are potent candidates for delivery of clarithromycin in acidic environment.     

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.     

Preparation and characterization of hybrid pH-sensitive hydrogels of chitosan-co-acrylic acid for controlled release of verapamil

In the present work crosslinked hydrogels based on chitosan (CS) and acrylic acid (AA) were prepared by free radical polymerization with various feed compositions using N,N methylenebisacrylamide (MBA) as crosslinking agent. Benzoyl peroxide was used as catalyst. Fourier transform infrared spectra (FTIR) confirmed the formation of the crosslinked hydrogels. This hydrogel is formed due to electrostatic interaction between cationic groups in CS and anionic groups in AA. Prepared hydrogels were used for dynamic and equilibrium swelling studies. For swelling behavior, effect of pH, polymeric and monomeric compositions and degree of crosslinking were investigated. Swelling studies were performed in USP phosphate buffer solutions of varying pH 1.2, 5.5, 6.5 and 7.5. Results showed that swelling increased by increasing AA contents in structure of hydrogels in solutions of higher pH values. This is due to the presence of more carboxylic groups available for ionization. On the other hand by increasing the chitosan content swelling increased in a solution of acidic pH, but this swelling was not significant and it is due to ionization of amine groups present in the structure of hydrogel. Swelling decreased with increase in crosslinking ratio owing to tighter hydrogel structure. Porosity and sol-gel fraction were also measured. With increase in CS and AA contents porosity and gel fraction increased, whereas by increasing MBA content porosity decreased and gel fraction increased. Furthermore, diffusion coefficient (D) and the network parameters i.e., the average molecular weight between crosslinks (M_c), polymer volume fraction in swollen state (V_2s), number of repeating units between crosslinks (M_r) and crosslinking density (q) were calculated using Flory-Rehner theory. Selected samples were loaded with a model drug verapamil. Release of verapamil depends on the ratios of CS/AA, degree of crosslinking and pH of the medium. The release mechanisms were studied by fitting experimental data to model equations and calculating the corresponding parameters. The result showed that the kinetics of drug release from the hydrogels in both pH 1.2 and 7.5 buffer solutions was mainly non-Fickian diffusion.     

pH-sensitive hydrogels based on semi-interpenetrating network (semi-IPN) of chitosan and polyvinyl pyrrolidone for clarithromycin release

The aim of this study was to develop a pH-sensitive chitosan/polyvinyl pyrrolidone (PVP) based controlled drug release system for clarithromycin. The hydrogels were synthesized by cross-linking chitosan and PVP blend with glutaraldehyde to form a semi-interpenetrating polymer network (semi-IPN). These semi-IPNs were studied for their content uniformity, swelling index (SI), mucoadhesion, wettability, in vitro release and their release kinetics. The hydrogels showed more than 97% content of clarithromycin. These hydrogels showed high swelling and mucoadhesion under acidic conditions. The swelling may be due to the protonation of a primary amino group on chitosan. In acidic condition, chitosan would be ionized, and adhesion could have occurred between the positively charged chitosan and the negatively charged mucus. In the alkaline condition, less swelling and mucoadhesion was noticed. In vitro release study revealed that formulation containing chitosan (2% w/v) and PVP (4% w/v) in the ratio of 21:4 showed complete drug release after 12?h. Release profile showed that all the formulations followed non-Fickian diffusion mechanism. The cross-linking and compatibility of clarithromycin in the formulation was studied by Fourier transform infrared (FTIR) spectroscopic analysis, differential scanning calorimetry (DSC) and powder X-ray diffraction (p-XRD) study, which confirmed proper formation of semi-IPN and stability of clarithromycin in the formulations. The surface morphology of semi-IPN was studied before and after dissolution in simulated gastric fluid (SGF, pH 1.2) which revealed pores formation in membrane after dissolution. The results of study suggest that semi-IPNs of chitosan/PVP are potent candidates for delivery of clarithromycin in acidic environment.     

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).     

In vitro release dynamics of model drugs from psyllium and acrylic acid based hydrogels for the use in colon specific drug delivery

Psyllium is medicinally important gel forming polysaccharides. Keeping in view, the pharmacological importance of psyllium and drug delivery devices based on hydrogels, psyllium, if suitably tailored to prepare the hydrogels, can act as the double potential candidates for the novel drug delivery systems. Therefore, it is an attempt to prepared psyllium and acrylic acid based pH sensitive novel hydrogels by using N,N'-methylenebisacrylamide (N,N-MBAAm) as crosslinker and ammonium persulfate (APS) as initiator for the use in colon specific drug delivery. The present paper discusses the swelling kinetics of the hydrogels and release dynamics of model drugs (tetracycline hydrochloride, insulin and tyrosine) from drug-loaded hydrogels, for the evaluation of the swelling mechanism and drug release mechanism from the polymeric networks .The effect of pH on the swelling kinetics and release pattern of drugs have been studied by varying the pH of the release medium. It has been observed that swelling and release of drugs from the hydrogels occurred through non-Fickian or anomalous diffusion mechanism in distilled water and pH 7.4 buffer. It shows that the rate of polymer chain relaxation and the rate of drug diffusion from these hydrogels are comparable.