交联透明质酸凝胶薄膜的制备及性能研究

用三偏磷酸钠(STMP)对透明质酸(HA)进行交联,制备出HA-STMP凝胶薄膜,研究了不同交联程度HA-STMP薄膜的吸水保水性能和体外降解性能。研究结果表明,实验中控制STMP与HA的结构单元比在1/5以上都可以得到成膜性能良好的交联薄膜;HA-STMP交联薄膜可以吸附自身质量7～10倍的水分,且随着交联程度的提高,薄膜的吸水能力下降,保水性能提高;交联改性能改善HA的耐降解性能,使高聚物在体内的存留时间延长,且耐降解性能随交联程度的增加而提高。     

交联透明质酸钠支架材料制备工艺优化及其体外抗酶降解性研究

以透明质酸钠浓度、交联剂投入量、反应温度、溶胀时间作为考察因素,抗酶系数作为评价指标,采用L9(34)正交设计表优化交联透明质酸钠支架材料制备工艺参数并建立支架的体外抗酶降解性测定方法。正交试验结果经直观和方差分析显示,透明质酸钠浓度、交联剂投入量具有显著性影响,在透明质酸钠浓度为5%,交联剂投入量为5%,反应温度40℃和溶胀时间4h的条件下,可以制得体外抗酶降解性较强的交联透明质酸钠支架材料,其可作为一种细胞支架用于软骨组织工程研究。     

可生物降解温敏凝胶PNMH-OSA的降解行为与释药性能

N-异丙基丙烯酰胺(NIPA)和丙烯酸甲酯(MA)通过自由基共聚形成线型大分子P(NIPA-MA),再用联胺取代MA嵌段上的甲氧基,得到一种多官能团的温敏大分子聚(N-异丙基丙烯酰胺-丙烯酸甲酯-丙烯酰肼)(PNMH),用它交联氧化的海藻酸钠(OSA),得到可生物降解的温敏凝胶PNMH-OSA。研究了PNMH的取代度(DS)、海藻酸钠的氧化程度(DO)、pH值和离子强度对PNMH-OSA凝胶降解性能的影响,同时以次甲基蓝(MB)和牛血清蛋白(BSA)为模拟药物,采用包埋法将药物载入凝胶中,研究了凝胶的释药行为。结果表明,凝胶降解速率随海藻酸钠的氧化程度、pH值增加而增加,随PNMH的取代度、离子强度增加而减慢;药物释放速率与药物的分子量和凝胶的降解速率有关。     

基于交联透明质酸的微针制备及性能

新型水凝胶微针具有安全包裹多相药物、药物持续、可控释放等优点,在微针透皮给药领域极具应用潜力.文中重点研究了交联透明质酸微针贴片的优化工艺,并对微针贴片进行了性能评价.在碱性条件下使用1,4-丁二醇二缩水甘油醚(BDDE)为交联剂对透明质酸进行交联,利用微浇注法制备交联透明质酸微针(cHA-MN),并优化其工艺.对所制...     

聚乙二醇共价交联海藻酸钠凝胶制备及其药物缓释性能

为了增强海藻酸钠凝胶的稳定性以及对药物的缓释效果,将海藻酸钠用聚乙二醇(PEG200)交联,在水溶液中用对甲苯磺酸催化、经过酯化反应合成了共价交联的海藻酸钠凝胶;通过红外光谱、热重分析和X-射线分析对产物进行了表征。与钙离子交联的海藻酸钠凝胶相比,共价交联海藻酸凝胶在仿生体液中结构稳定,在模拟体液中完全降解时间持续到60天。凝胶对牛血清白蛋白的载药率达到11.5%,显示出明显的缓释效应和pH响应性能,具有作为pH控释和缓释药物载体的应用前景。     

透明质酸交联衍生物的研究进展

由于天然透明质酸存在对透明质酸酶及自由基敏感使得在体内保留时间短、力学强度差等缺点,为此很多学者为了提高其抗降解性能和力学强度等展开了对透明质酸的化学改性的诸多研究。文章综述了近年来比较新颖的透明质酸交联技术,包括"点击化学"交联、光交联和自交联技术。同时论述了所获得透明质酸交联凝胶的性质,例如:可原位反应形成凝胶、良好的生物相容性、可生物降解和更便捷的操作性等。同时也展现了透明质酸交联凝胶在软组织填充、组织工程支架、药物载体和再生医学等方面的潜在应用前景。     

酸敏感型两亲性聚合物的制备和释药性能研究

以合成的PEG2000-Br为引发剂,甲基丙烯酸二乙基氨基乙酯(DEAM)为功能性单体,CuBr为催化剂,五甲基二乙烯基三胺(PMDETA)为配体,通过原子转移自由基聚合(ATRP)制备了两亲聚合物聚乙二醇-聚甲基丙烯酸二乙基氨基乙酯(PEG-PDEAM);并通过紫外、1 H-NMR等表征手段对聚合物的结构进行了表征;实验以荧光染料DPH为探针,分析探讨了两亲聚合物的临界胶束浓度(CMC)值,并以PEG-PDEAM为载体,阿霉素(DOX)为模型药物,分析了聚合物对脂溶性药物的包载能力,以及载药胶团在不同介质或温度下的药物控释能力。结果表明:PEG-PDEAM对DOX的最高包封率为64.62%,载药量为8.077%;DOX-PEG-PDEAM聚合物胶团有良好的酸响应能力,12h内可实现90%药物释放;并且该聚合物胶团亦具有一定的温度响应能力,在低温条件下释放效率显著的低于高温情况下。     

盐酸小檗碱β-环糊精聚合物微球的制备和释药性能研究

以β-环糊精为单体,环氧氯丙烷为交联剂,通过反相乳液聚合法和共沉淀法制备了盐酸小檗碱β-环糊精聚合物微球(BH-β-CDPM)。多媒体显微镜验证了β-CDPM的球形结构;紫外光谱分析研究表明,通过共沉淀法制备的微球对BH的包载性能较优,BH-β-CDPM的包封率最大为69.45%;通过对BH-β-CDPM的体外释药行为研究,发现介质的pH值对其释药效果影响较大,在碱性介质(pH=9.9)中缓释性能较好,中性介质释放较快,且药物投加量越低缓释越显著。BH-β-CDPM(30∶1)在pH=2.2的介质中药物的释药动力学过程附合Higuchi和Korsmeyer-Peppas模型,可见该条件下药物的释放主要是Fikc扩散过程。     

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。     

聚乳酸多孔微球的制备及释药性能

将聚乳酸(PLLA)/四氢呋喃(THF)溶液分散在甘油(连续相)中,通过自乳化结合热致相分离(TIPS)制备一系列PLLA多孔微球,微球由捆束状纳米纤维组成。通过改变PLLA浓度、(PLLA/THF)∶甘油比值、溶剂种类以及淬火温度等条件研究所得多孔微球结构与形貌。结果表明,PLLA的质量分数为2%~5%、m(PLLA/THF)∶m(甘油)=1∶3、-20℃和-196℃淬火均能得到形状规整的PLLA多孔微球。多孔微球孔隙率和比表面积最高可达95.44%和32.53m2/g。PLLA多孔微球对牛血清蛋白的药载量为0.355 mg/mg,30 h内释放率达到59.8%,是一种非常良好的药物缓释载体。     

Fast dissolving electrospun polymeric films of anti-diabetic drug repaglinide: formulation and evaluation

Abstract

Objective: Repaglinide is a well-known FDA approved drug from category of meglitinide; used for the treatment of diabetes. However, its use is limited because of its poor water solubility which leads to erratic drug absorption. Present work focuses on formulation and evaluation of polyvinyl alcohol (PVA)-polyvinyl pyrrolidone (PVP) nanofibers to counter this problem of poor water solubility.

Significance: Prepared nanofibers with hydrophilic polymers were expected to tackle the problem of poor water solubility.

Methods: Nanofibers were prepared by electrospinning technique with the optimization of parameters affecting final product. Further prepared formulation was characterized using various techniques.

Results: Successful development of drug loaded nanofibers was commenced utilizing electrospinning technique. Further casted film of same polymeric blend was prepared and compared with nanofibers. Optimized nanofibers showed an average diameter of 600–800?nm with smooth surface morphology. Prepared nanofibers and casted film was analyzed in terms of surface morphology, mechanical strength, solid state of drug present, effects of hydrogen bond formation and drug release profile. Results from the glucose tolerance test suggested both the formulations to be having better control over glucose levels as compared to free drug.

Conclusion: Overall developed nanofibers presented themselves to be potential drug delivery candidates for drugs having poor water solubility.     

室温自交联水性聚氨酯分散体的合成与表征

采取新工艺以甲苯二异氰酸酯(TDI-80)、聚醚二元醇(N220)、三羟甲基丙烷(TMP)、二羟甲基丙酸(DMPA)、环氧树脂(E-20)、甲基丙烯酸甲酯(MMA)等原料合成了聚氨酯一丙烯酸酯复合分散体(PUA-1),通过双丙酮丙烯酰胺(DAAM)引入酮羰基和己二酸二酰肼(ADH)引入肼基,合成了室温自交联复合分散体(PUA-2).探讨了DMPA,MMA,DAAM和ADH的加入量对分散体和涂膜性能的影响.通过傅立叶红外光谱(FTIR)、示差扫描量热仪(DSC)、接触角测量仪对PUA-1及PUA-2进行了表征.结果表明,当DMPA,MMA,DAAM的含量[占聚氨酯(PU)的质量分数]分别为6%,25%,2.5%及ADH与DAAM的摩尔比为1时,分散体和涂膜的综合性能较好;酮肼间发生了交联反应,交联使得胶膜的耐水性和力学性能得到了提高.     

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.     

多孔P(NIPAm-co-AAm)水凝胶对蛋白质控制释放的研究

采用冷冻聚合法制备了多孔结构的P(NIPAm-co-AAm)智能水凝胶,选用牛血清白蛋白(BSA)为模型药物分子,通过后包裹技术负载蛋白质药物,考察了多孔水凝胶中蛋白质药物的载药量和体外释放行为,研究了不同干燥处理方法对载药后水凝胶的药物控释性能的影响,并且与传统方法制备的P(NIPAmco-AAm)水凝胶进行了药物控释性能对比实验。实验结果表明,在凝胶中引入多孔结构使得P(NIPAm-coAAm)水凝胶的药物载药量和释放量得到了显著的提高。不同的干燥处理方法对多孔P(NIPAm-co-AAm)水凝胶的药物释放影响很大,载药后的凝胶采用冰箱冷冻干燥处理,可使蛋白质药物有较好的缓释效果。     

Influence of hydroxypropyl methylcellulose mixture,apparent viscosity,and tablet hardness on drug release using a 2(3) full factorial design

This study investigates the effects of three factors: (1) use of a mixture of two different grades of hydroxypropyl methylcellulose (HPMC), (2) apparent viscosity, and (3) tablet hardness on drug release profiles of extended-release matrix tablets. The lot-to-lot apparent viscosity difference of HPMC K15M on in vitro dissolution was also investigated. Four test formulations were made, each containing 10% of a very water-soluble active pharmaceutical ingredient (API), 32% HPMC K15M, or a mixture of HPMC K100LV and HPMC K100M, 56% diluents, and 2% lubricants. Each formulation was made at two hardness levels. A 2³ full factorial design was used to study various combinations of the three factors using eight experiments conducted in a randomized order. Dissolution studies were performed in USP apparatus I. The values of t_50% (time in which 50% drug is released) and t_lag (lag time, the time taken by the matrix tablet edges to get hydrated and achieve a state of quasi-equilibrium before erosion and the advance of solvent front through the matrix occur) were calculated from each dissolution profile. The similarity factor (f₂) was also calculated for each dissolution profile against the target dissolution profile. A simple Higuchi-type equation was used to analyze the drug release profiles. Statistical analysis using analysis of variance (ANOVA) and similarity factor (f₂) values calculated from the data indicated no significant difference among the t_50% values and dissolution profiles respectively for all formulations. Within the 3.3-6 kp hardness range investigated, dissolution rates were found to be independent of tablet hardness for all the formulations. Although significantly shorter lag times were observed for the tablets formulated with low- and high-viscosity HPMC mixtures in comparison to those containing a single grade of HPMC, this change had no significant impact on the overall dissolution profiles indicated by the similarity factor f₂ values. From this study it can be concluded that lot-to-lot variability in apparent viscosity of HPMC should not be a concern in achieving similar dissolution profiles. Also, results indicated that within the viscosity range studied (12,000-19,500 cps) an HPMC mixture of two viscosity grades can be substituted for another HPMC grade if the apparent viscosity is comparable. Also, the drug release is diffusion-controlled and depends mostly on the viscosity of the gel layer formed.     

海藻酸钠-胰蛋白酶微球的制备及药物释放性能

通过离子凝胶法制备出球形完好的海藻酸钠-胰蛋白酶微球.红外分析表明,微球中凝胶基质通过海藻酸钠的-COO-与Ca2+发生静电作用交联形成.SEM观察显示微球中存在蛋格结构及孔洞.考察了不同因素对微球载药率、包封率和体外释药率的影响.结果表明,海藻酸钠水溶液浓度越高释药率越低,当海藻酸钠与胰蛋白酶质量比为4,海藻酸钠水溶...     

V2O5溶胶-凝胶涂膜法及涂膜性能分析

以V2O5溶胶凝胶为原料,采用旋涂法、浸涂法、喷涂法和刷涂法在各种衬底上涂制V2O5薄膜。对4种涂膜方法以及胶体性能对涂膜的影响进行了分析;给出了薄膜厚度与主要影响因素之间的关系。     

The role of fillers and sodium metabisulfite on drug release from aged polyox tablets

Polyethylene oxides (PEOs) are extensively used to control the release rate of drugs from matrices. Unfortunately, polyox polymers are prone to oxidation under high temperature and relative humidity. The aim of this study was to investigate the effect of sodium metabisulfite as an antioxidant to overcome the drug release changes from polyox matrices (PEO 301 and 303) when stored at 40?°C. The effect of different types of fillers (lactose, mannitol and dicalcium phosphate dihydrate) on stability of diltiazem HCl release profiles was also investigated. Generally, the presence of sodium metabisulfite stabilized the release of drug from PEO matrices stored at 40?°C for 8 weeks. Whilst the absence of metabisulfite caused an increase in drug release from polyox matrices when stored at 40?°C. The results indicate that all three concentrations (0.25, 0.5 and 1% w/w) of sodium metabisulfite were able to overcome structural changes of polyox samples hence stabilizing the drug release. The results also showed that the incorporation of fillers in polyox matrices reduced the sensitivity of drug release when stored at elevated temperature. This indicates that when these excipients were used there was no need to incorporate additional antioxidant. DSC results showed that there was no difference in the melting points of fresh polyox samples and aged polyox samples containing sodium metabisulfite, whereas the melting point of aged polyox samples without sodium metabisulfite were lower than fresh polyox samples. This indicates that the presence of metabisulfite is essential to stabilize polyox samples.