温度及pH敏感水凝胶的合成及其在生物大分子控制释放中？…

描述了含不同羧基量的两个ｐＨ及温度敏感水凝胶的制备方法。所得的凝胶有３７℃和ｐＨ１．４条件下不胶胀，面在３７℃ｐＨ７．４条件下则溶胀。以木瓜酶为模型蛋白质并将其吸附在这些凝胶上，在不同条件下比较了木瓜酶的生物活性。结果表明，当凝胶中羧基含量较高时，酶的保留活力较高。在３７℃和ｐＨ．４条件下，在一个较短的时间内吸附在凝胶中的大部分木瓜酶可以释放出来。这类凝胶可用于蛋白质的ｐＨ及温度控制释放。     

聚丙烯酸钾／羧甲基纤维素钠半互穿网络水凝胶的两步水溶液合成及其药物释放

以N,N’-亚甲基双丙烯酰胺为交联剂、过硫酸铵和焦亚硫酸钠为氧化还原引发剂，采用新型两步水溶液聚合法制备了聚丙烯酸钾／羧甲基纤维素钠（PAA／CMC-Na）半互穿网络水凝胶．对其溶胀动力学、离子强度敏感性和pH敏感性进行了研究．探讨了PAA／CMC-Na半互穿网络水凝胶对荼碱的释放行为，实验结果表明所吸收的茶碱在盐溶液中90min内释放率可达90％，释放规律遵循Fiekian扩散机制。     

壳聚糖硫酸酯pH敏感性水凝胶的制备及其性能

壳聚糖硫酸酯（SCS）为一种典型的两性聚电解质。在本文中,以均相合成的方法制得高含硫量的SCS。以戊二醛（GA）作为交联剂,采用化学交联的方法制备了一种新型的水凝胶-SCS水凝胶。利用环境扫描电镜（ESEM）对SCS水凝胶的形貌进行表征,并研究了制备条件（包括SCS浓度、GA用量以及SCS的硫酸根含量）和环境条件（包括介质、溶液pH值）对SCS水凝胶溶胀度的影响。实验结果表明,所制得的SCS水凝胶对介质的pH值变化具有敏感性;SCS水凝胶的溶胀度随着SCS浓度的增加而增大,随着交联剂用量的增加和SCS硫酸根含量的增大而减小。SCS水凝胶在氯化钠溶液中的溶胀度远远低于其在水中的溶胀度。     

聚甲基丙烯酰吗啉枝化壳聚糖梳型聚合物的pH敏感性及其对辅酶A的控制释放

利用马来酸酐单酰化壳聚糖(CS-Ma)与甲基丙烯酰吗啉(MAMP)共聚, 合成了一种新型梳型聚合物-聚甲基丙烯酰吗啉枝化壳聚糖[P(CS-Ma-MAMP)],并用FTIR、H1-NMR对其结构进行表征, 聚合物的分子量用凝胶渗透色谱(GPC)测定.用UV研究了其对辅酶A(Co A)的控制释放,结果表明在24℃、pH=6.8时,随着聚合物水溶液浓度的增大,对辅酶A的控制量就增多;pH在3.7～9之间变化时,可以通过调节聚合物水溶液的pH实现对辅酶A的控制释放,并初步探讨了其控制释放的机理.     

温度及pH敏感水凝胶的合成及其在生物大分子控制释放中的应用

描述了含不同羧基量的两个系列的ｐＨ及温度敏感水凝胶的制备方法。所得的凝胶在３７℃和ｐＨ１．４条件下不溶胀，而在３７℃ｐＨ７．４条件下则溶胀。以木瓜酶为模型蛋白质并将其吸附在这些凝胶上，在不同条件下比较了木瓜酶的生物活性。结果表明，当凝胶中羧基含量较高时，酶的保留活力较高。在３７℃和ｐＨ７．４条件下，在一个较短的时间内吸附在凝胶中的大部分木瓜酶可以释放出来。这类凝胶可望用于蛋白质的ｐＨ及温度控制释放。     

温度/pH敏感性壳聚糖-聚乙烯吡咯烷酮水凝胶的制备

以壳聚糖（CS）和聚乙烯基吡咯烷酮（PVP）为原料,戊二醛为交联剂,硝酸铈铵为引发剂,制备了具有温度和pH双重敏感性的CS/PVP水凝胶。考察了制备条件对水凝胶溶胀率的影响,结果表明,在PVP∶CS（质量比）=10∶1,0.3%（质量分数,下同）交联剂（相对于PVP）,2.5%引发剂,60℃反应10 h的条件下,获得的...     

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。     

PAA-Na/PVA半互穿网络水凝胶的离子强度及pH敏感性

采用水溶液聚合法制备了聚丙烯酸钠(PAA-Na)/聚乙烯醇(PVA)半互穿网络水凝胶,研究了水凝胶在不同pH溶液、不同浓度NaCl与CaCl2溶液中的溶胀行为,结果表明,溶胀比随丙烯酸含量增大而增加,在碱性溶液中的溶胀度明显高于酸性溶液,溶胀平衡凝胶在酸性及碱性条件下均出现收缩,在pH=2和pH=12溶液中反复交换时,表现出可逆溶胀-退溶胀性能,具有较好的pH敏感性,凝胶在不同浓度NaCl与CaCl2溶液中溶胀性表明,溶液的离子强度及阳离子的电荷数对凝胶溶胀行为有较大影响。     

包埋在温度及pH值敏感水凝胶中的阿司匹林的控制释放研究

直接将Ｎ－异丙基丙烯酰胺（ＮＩＰ）、丙烯酸和Ｎ，Ｎ′－甲叉双丙烯酰胺交联共聚合成了温度及ｐＨ值敏感水凝胶，包埋在此水凝胶中的抗结肠癌药物阿司匹林的释放随温度、介质ｐＨ值和药物制剂方式的变化而显著不同。在ｐＨ＝７．４的介质中３７℃时阿司匹林在水凝胶膜中的释放比２５℃时快，而在３７℃下ｐＨ＝７．４的介质中阿司匹林的释放比ｐＨ＝１．０快得多，后者在较长时间内仍释放一小部分，因此可将阿司匹林大部分定向到肠中释放。将膜剂改成粒剂后，可以获得较好的释放效果。     

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。     

Preparation and characterization of pH sensitive comb-shaped chitosan material for the controlled release of coenzyme A

A novel kind of pH sensitive comb-shaped copolymer P(CS-Ma-PEGMA) was synthesized with chitosan (CS), maleic anhydride (Ma) and Poly (ethylene glycol) methacrylate (PEGMA) by grafting and co-polymerization. The structure of P(CS-Ma-PEGMA) was characterized by FT-IR and ¹H-NMR, and it was found that PEGMA was grafted onto CS and PEGMAylated chitosan was soluble. The copolymer was subjected to coenzyme A adsorption study in order to assess its application in biomedical area. The factors affecting release behavior, such as concentration and pH were discussed in this paper. The higher concentration of the copolymer showed higher absorbance peak than the lower one. The pH of the solution also had significant impact on the release of coenzyme A, and the mechanism of adsorption was suggested. The results suggested that the novel copolymer could be used as drug delivery carrier.     

PAA/PVA互穿网络水凝胶膜的制备和药物输送研究

采用自由基溶液聚合和连续的互穿网络技术,以氧化还原引发体系为引发剂、化学交联聚丙烯酸(PAA)和聚乙烯醇(PVA)制备了一系列PAA/PVA水凝胶膜.ATR-FTIR光谱表明,网络组成之间形成了新的相互作用的氢键,DSC分析表示网络组成具有良好的热力学相容性.膜在各种介质中的溶胀性质表明:因PAA的亲水性强于PVA,溶胀比随PAA的增多而提高.以阳离子化合物结晶紫为模板药物考察了在不同的pH缓冲溶液中的释放行为,结果表明,药物的释放能力可以通过改变体系的pH值加以调控.     

Pharmacokinetics of a novel nifedipine and pH-sensitive N-succinyl chitosan/alginate hydrogel bead in rabbits

Context: A novel N-succinyl chitosan/alginate hydrogel bead was prepared by the ionic gelation method for controlled delivery of nifedipine (NF). Objective: The delivery behavior of NF from the hydrogel bead was studied in rabbit body. Materials and methods: Nitrendipine was used as the internal standard and the concentration of NF in serum was determined by reversed-phase high-performance liquid chromatography. Results: The assay was linear from 5 to 755 ng/mL. The limit of quantitation for NF was 5 ng/mL in serum, and the recovery was greater than 90%. The method was used to determine the concentration–time profiles of NF in the serum. The pharmacokinetic parameters were calculated by Drug and Statistics (ver 1.0) program. The mean Cmax was 320.2 ± 71.3 μg/L, the mean Tmax was 3.2 ± 0.5 hours, the mean t1/2 was 6.60 ± 2.17 hours, the mean AUC0-24 was 2.03 ± 0.25 mg h/L, the mean AUC0-∞ was 2.50 ± 0.36 mg h/L, the mean MRT0-24 was 8.57 ± 0.19 hours, and the mean MRT0-∞ was 15.2 ± 1.8 hours. Discussion and conclusion: The pharmacokinetic characteristics were found by a two-compartment model following the oral administration of NF-loaded N-succinyl chitosan/alginate hydrogel beads in rabbits.     

Development of novel pH-sensitive nanoparticles loaded hydrogel for transdermal drug delivery

Objective: Difference of pH that exists between the skin surface and blood circulation can be exploited for transdermal delivery of drug molecules by loading drug into pH-sensitive polymer. Eudragit S100 (ES100), a pH-sensitive polymer having dissolution profile above pH 7.4, is used in oral, ocular, vaginal and topical delivery of drug molecules. However, pH-sensitive potential of this polymer has not been explored for transdermal delivery. The aim of this research work was to exploit the pH-sensitive potential of ES100 as a nanocarrier for transdermal delivery of model drug, that is, Piroxicam.

Methods: Simple nanoprecipitation technique was employed to prepare the nanoparticles and response surface quadratic model was applied to get an optimized formulation. The prepared nanoparticles were characterized and loaded into Carbopol 934 based hydrogel. In vitro release, ex vivo permeation and accelerated stability studies were carried out on the prepared formulation.

Results: Particles with an average size of 25–40?nm were obtained with an encapsulation efficiency of 88%. Release studies revealed that nanoparticles remained stable at acidic pH while sustained release with no initial burst effect was observed at pH 7.4 from the hydrogel. Permeation of these nanocarriers from hydrogel matrix showed significant permeation of Piroxicam through mice skin.

Conclusion: It can be concluded that ES100 based pH-sensitive nanoparticles have potential to be delivered through transdermal route.     

多功能壳聚糖水凝胶医用材料的功能性研究

作为一类兼具应用价值和经济效益的新型功能高分子材料,水凝胶越来越受关注。以天然可降解的壳聚糖为载体,通过自由基接枝共聚法制备了壳聚糖水凝胶,重点研究了其吸附性及药物控释性能。结果表明:该水凝胶20d左右可以完全降解,降解性能良好。在25℃条件下,铜离子浓度为1200mg/L时,壳聚糖水凝胶对铜离子的平衡吸附量可达225.8mg/g。以亚甲基蓝为药物模型的控释实验结果表明,温度以及初始药物投加量对控释性能影响较大,48h累积释放率达70%左右,可在一定程度上实现缓释控释效果。     

The effect of pH,buffer capacity and ionic strength on quetiapine fumarate release from matrix tablets prepared using two different polymeric blends

The objective of this study was to investigate the effect of the different physiological parameters of the gastrointestinal (GI) fluid (pH, buffer capacity, and ionic strength) on the in vitro release of the weakly basic BCS class II drug quetiapine fumarate (QF) from two once-a-day matrix tablet formulations (F1 and F2) developed as potential generic equivalents to Seroquel^® XR. F1 tablets were prepared using blends of high and low viscosity grades of hydroxypropyl methylcellulose (HPMC K4M and K100LV, respectively), while F2 tablets were prepared from HPMC K4M and PEGylated glyceryl behenate (Compritol^® HD5 ATO). The two formulations attained release profiles of QF over 24?h similar to that of Seroquel^® XR using the dissolution medium published by the Food and Drug Administration (FDA). A series of solubility and in vitro dissolution studies was then carried out using media that simulate the gastric and intestinal fluids and cover the physiological pH, buffer capacity and ionic strength range of the GIT. Solubility studies revealed that QF exhibits a typical weak base pH-dependent solubility profile and that the solubility of QF increases with increasing the buffer capacity and ionic strength of the media. The release profiles of QF from F1, F2 and Seroquel^® XR tablets were found to be influenced by the pH, buffer capacity and ionic strength of the dissolution media to varying degrees. Results highlight the importance of studying the physiological variables along the GIT in designing controlled release formulations for more predictive in vitro–in vivo correlations.     

A comparative study of chitosan and poloxamer based thermosensitive hydrogel for the delivery of PEGylated melphalan conjugates

Abstract

Objective: Although the melphalan (ML) used extensively for the management of breast cancer, its clinical application is limited due to significant hemolytic activity. In the present work, a comparative analysis of two distinct in situ-based thermogelling polymers of PEGylated ML was performed.

Methods: Briefly, the PEGylated conjugate of the melphalan (MLPEG 5000) for local and sustained drug release action is loaded into two different thermogelling polymeric systems, namely chitosan- and poloxamer-based systems. The synthesized conjugate was loaded to a chitosan (MLP 5000) and poloxamer-based (MPX-CG) thermogelling injectable hydrogels. These thermogelling hydrogels were evaluated for in vitro hydrolysis, in vitro hemolytic activity. and in vitro anticancer activity.

Results: The lower percent cumulative hydrolysis was witness for both the hydrogels. MPX-CG and MLP 5000 hydrogels as predicted had shown lower percent cumulative hydrolysis of 3.31?±?0.1 and 1.67?±?0.1 after 6?h. The percentage hemolysis of MPX-CG and MLP 5000 even at a concentration of 32?µg/ml was found to be 39.23?±?1.24% and 34.23?±?2.24%, observed at 1?h, respectively. Both the hydrogels showed similar anticancer pattern, the MPX-CG hydrogel showed low cell viability of 8.4?±?1.1% at a concentration of 150?µM and the MLP-5000 hydrogel showed slight higher cell viability (13.12?±?5.4%) as compared with MPX-CG hydrogel.

Conclusion: Hence, from the present study it can be well understood that both the chitosan- and the poloxamer-based thermogelling hydrogel proves to be an effective drug delivery systems for the delivery of the PEGylated conjugates.     

聚离子复合物胶束的制备及其对辅酶A的控制释放

用RAFT活性可控聚合法合成了全水亲性嵌段共聚物聚(N-乙烯基吡咯烷酮)-b-聚(2-丙烯酰胺-2-甲基丙磺酸)(PVP-b-PAMPS)和聚(N-乙烯基吡咯烷酮)-b-聚甲基丙烯酸二甲氨基乙酯(PVP-b-PD-MAEMA).二者在水溶液中复合即可形成聚离子复合物(PIC)胶束,并利用动态光散射法(DLS)和透射电镜(TEM)表征了该胶束的粒径、粒径分布以及形貌.研究结果表明,所制备的胶束外形大致呈球状,粒径在155nm左右,且粒径分布较窄.以辅酶A为模型分子,负载在胶束内进行药物控制释放.研究结果表明,辅酶A的释放受溶液pH的影响,该聚离子复合物胶束可以用作药物控释载体.