丙烯酸-Pluronic(R) F127接枝共聚物的流变学性质

目的 研究丙烯酸Plurinic(R) F127接枝共聚物的流变学性质.方法 用同轴圆筒流变仪测定共聚物溶液的流变参数.结果 共聚物溶液在较低浓度下具有温度敏感的原位凝胶特性.结论 丙烯酸-Pluronic(R) F127接枝共聚物作为一种具有温度敏感原位凝胶性质的材料,具有广泛的应用前景.     

丙烯酸-Pluronic~ F127接枝共聚物的流变学性质

目的研究丙烯酸Pluronic F127接枝共聚物的流变学性质。方法用同轴圆筒流变仪测定共聚物溶液的流变参数。结果共聚物溶液在较低浓度下具有温度敏感的原位凝胶特性。结论丙烯酸-Pluronic F127接枝共聚物作为一种具有温度敏感原位凝胶性质的材料,具有广泛的应用前景。     

多西他赛Pluronic F127聚合物胶束的制备与表征

目的制备多西他赛(DTX)的F127聚合物胶束,对其药剂学特征进行评价。方法薄膜分散法制备胶束,并在单因素考察的基础上,以正交试验优化处方;透射电镜观察胶束形态;粒度分布测定仪测定其粒径、粒度分布;离心过滤法测定胶束的包封率和载药量;以DTX注射液作对照,采用动态膜透析法考察载药胶束的体外释药情况。结果薄膜分散法制备的胶束呈球形或类球形,平均粒径为(30.2±2.56)nm,平均包封率为(86.66±2.46)%,平均载药量为(0.42±0.01)%;体外释放实验结果表明该胶束具有一定的缓释能力。结论该胶束制备工艺简单,成型好,包封率高,具有一定的缓释能力。     

载多烯紫杉醇Solutol HS15/Pluronic F127混合胶束及叶酸接枝的Solutol HS15/Pluronic F127载药混合胶束的制备、优化及对比表征(英文)

采用薄膜水化法制备了载多烯紫杉醇Solutol HS15/Pluronic F127混合胶束(SF-DTX)及叶酸接枝的Solutol HS15/Pluronic F127载药混合胶束(FSF-DTX)。体外表征实验表明,两种载药混合胶束体系均呈球型,粒径分别为(22.2±0.43)nm,(24.3±0.26)nm;均具备较高包封率,SF-DTX为99.05%,FSF-DTX为90.28%,且均有缓释特性。同时,细胞摄取及细胞毒性实验结果表明两种混合胶束体系均在一定程度上可以逆转肿瘤多药耐药性(MDR),且FSF较之于SF胶束体系能更明显增强耐药人口腔上皮细胞癌细胞(KBv)对DTX的摄取,是一种潜在的肿瘤靶向性载药体系。     

丙烯酸-泊洛沙姆407共聚物的合成及其原位胶凝性质

目的制备丙烯酸和泊洛沙姆407构成的共聚物,研究其温度敏感的原位胶凝性质。方法将泊洛沙姆407溶于丙烯酸单体,引发聚合反应,产物用红外光谱和凝胶渗透色谱表征。用旋转黏度计测定共聚物水溶液的黏度随温度的变化。以维生素B12为模型药物,研究药物的释放性质。结果较低浓度的丙烯酸泊洛沙姆407共聚物水溶液具有受热原位胶凝的性质,其胶凝特征与共聚物的组成、浓度、溶液pH等有关,共聚物凝胶可延缓药物释放。结论丙烯酸泊洛沙姆407共聚物可望应用于黏膜给药的原位凝胶递药系统。     

温敏型原位凝胶的热力学及流变学性质研究

目的:以磷酸川芎嗪为模型药物,探讨运用泊洛沙姆P407(P407)制备鼻用温敏型原位凝胶的可行性。方法:采用搅拌转子法测定不同处方磷酸川芎嗪原位凝胶的胶凝温度(胶凝温度:T);在不同温度下,以旋转式黏度计测定加入不同浓度辅料后P407溶液的黏度,以考察黏度随温度的变化规律。结果:P407溶液浓度越高,T越低;辅料的加入可以使P407溶液T升高,而处方药物和等渗调节剂(0.9%NaCl)使P407溶液T降低。当温度升高时,P407黏度增大,而辅料的加入会使P407黏度突变点的温度升高,黏度变小。结论:通过调节P407溶液的浓度或加入一定量辅料的方法,可以使TMPP原位凝胶在鼻腔温度(33℃左右)下胶凝,从而达到增大生物利用度和减少给药流失的要求。     

乙酸异丁酸蔗糖酯原位凝胶流变学性质的研究

原位凝胶易于注射,注射后在体内发生相变,迅速转变为药物贮库的传递系统。原位凝胶中一种较好的小分子基质为乙酸异丁酸蔗糖酯(sucroseacetate isobutyrate,SAIB)[1,2],具有良好的生物相容性,在体内可被酶降解并逐渐代谢[3~5],其黏度超过100 Pa·s。与聚合物不同,当浓度高达85%     

甲基丙烯酸氨烷基酯共聚物(E型)游离膜性质的考察

目的研究甲基丙烯酸氨烷基酯共聚物(E型)游离膜的机械性质和透湿性,考察其影响因素。方法采用平面铸膜法制备游离膜,考察成膜温度,成膜时间,增塑剂用量和膜厚度对游离膜机械性质和透湿性的影响。进行游离膜拉伸试验,以拉伸强度(σ_M)、断裂伸长率(ε)和杨氏弹性模量(E)评价游离膜的机械性质;采用杯法测定游离膜的透湿系数,评价其透湿性。结果成膜温度、膜厚度和增塑剂浓度对甲基丙烯酸氨烷基酯共聚物(E型)游离膜的透湿性和机械性质有影响,而成膜时间对游离膜性质影响不大。结论根据实验结果,考虑流化床包衣的情况,初步确定:增塑剂DBS用量为10%(按聚合物质量计),包衣温度为30℃,于烘箱中40℃下老化8 h。对游离膜性质及影响因素考察可以为处方设计和包衣工艺提供参考。     

pH敏感聚(2-乙基-2-噁唑啉)-壳聚糖-阿霉素共聚物胶束的制备及性质考察

目的合成pH敏感两亲性接枝共聚物聚(2-乙基-2-噁唑啉)-壳聚糖-阿霉素(PEOz-g-CS-HyzDOX),采用透析法制备阿霉素pH敏感两亲性共聚物胶束并对其相关的制剂学性质、细胞抑制及细胞摄取行为进行考察。方法分别利用透射电镜(TEM)、动态光散射法(DLS)和zeta电位分析仪对胶束的形态、粒径和表面电位进行表征;采用透析法考察载药聚合物胶束的体外释放行为;采用MTT法考察聚合物胶束的细胞抑制作用。结果反应产物使用红外及核磁表征,确定为目标产物;PEOz-g-CS-Hyz-DOX聚合物胶束载药量为4.2%。采用透析法制备的载阿霉素聚(2-乙基-2-噁唑啉)-壳聚糖丁二酸单甲酯胶束(PEOz-g-CSMS/DOX)载药量可达5.62%,包封率为59.35%;两种胶束的粒径均较小且粒径分布很窄,胶束粒子为类球形且分散良好;两种胶束释药行为体现pH敏感性;PEOz-g-CS-Hyz-DOX聚合物胶束体外细胞毒作用及细胞摄取均优于PEOz-g-CSMS/DOX胶束和阿霉素溶液。结论以壳聚糖为载体的化学腙键释药胶束作为抗肿瘤药物的药物传递系统具有可行性及良好的应用前景。     

Pluronic F127-g-poly(acrylic acid) copolymers as in situ gelling vehicle for ophthalmic drug delivery system

To prolong the precorneal resident time and improve ocular bioavailability of the drug, Pluronic F127-g-poly(acrylic acid) copolymers were studied as in situ gelling vehicle for ophthalmic drug delivery system. The rheological properties and in vitro drug release of Pluronic-g-PAA copolymer gels were investigated. The rheogram and in vitro drug release studies indicated that the drug release rates decreased as acrylic acid/Pluronic molar ratio and copolymer solution concentration increased. But the drug concentration had no obvious effect on drug release. The release rates of the drug from such copolymer gels were mainly dependent on the gel dissolution. In vivo resident experiments showed the drug resident time and the total resident amount in rabbit's conjunctiveal sac increased by 5.0 and 2.6 folds for in situ gel, compared with eye drops. The decreased loss angle at body temperature and prolonged precorneal resident time also indicated that the copolymer gels had bioadhesive properties. These in vivo experimental results, along with the rheological properties and in vitro drug release studies, demonstrated that in situ gels containing Pluronic-g-PAA copolymer may significantly prolong the drug resident time and thus improve bioavailability. Pluronic-g-PAA copolymer can be a promising in situ gelling vehicle for ophthalmic drug delivery system.     

The effect of water-soluble polymers, PEG and PVP, on the solubilisation of griseofulvin in aqueous micellar solutions of Pluronic F127

The purpose of this study was to investigate the possibility of enhancing the solubilisation capacity of micellar solutions of Pluronic F127 for the poorly water-soluble drug griseofulvin by co-formulating with a water-soluble polymer. The effect of the addition of the polyethylene glycols PEG6000 and 35000, and the poly(vinylpyrrolidone)s PVP K30 and K90, on the solubilisation capacity of 1wt% solutions of Pluronic F127 was related to the effect of these additives on particle size as determined by dynamic light scattering measurements. The addition of PEG35000 to 1wt% F127 solutions significantly increased the solubility capacity expressed in terms of unit weight of F127; PVP K90 had a smaller effect but no enhancement was noted following the addition of PEG6000 or PVP K30. Solubilisation enhancement was thought to be a consequence of the association of the polymers with the E-blocks of the micelle corona so providing an expanded region of reduced polarity for drug solubilisation.     

Development and in vitro evaluation of insulin-loaded buccal Pluronic F-127 gels

Insulin-loaded buccal Pluronic F-127 (PF-127) gel formulations were fabricated to study the effect of PF-127 concentration, insulin concentration, presence of salt, addition of polymer, and permeation enhancer on their gelation time, mucoadhesion force, release and permeation characteristics of insulin from the gels. Thereafter, the principle of statistical optimization to prepare a gel formulation having the potential for buccal delivery of basal insulin in diabetic patients was employed. The gelation time decreased as the concentration of PF-127 increased. Presence of salts as well as addition of polymer, such as methyl cellulose (MC) and hydroxypropylmethyl cellulose (HPMC) decreased the gelation time. An increase in PF-127 concentration and addition of MC and HPMC increased the mucoadhesion force of the gel formulations. Release and permeation of insulin from the gel formulations decreased with increased concentration of PF-127, presence of salts, and addition of MC and HPMC. Permeation of insulin from the optimized gel formulation was 93.17 (± 0.058, n?=?3)?μg/cm² which was not only found in close agreement with predicted results from the model equations used for the formulation optimization but also considered comparable to clinical setting. Therefore, the development of optimized buccal insulin-loaded Pluronic F-127 gels using a statistical experimental design is feasible.     

F127/SWCNTs对P-gp底物在大鼠小肠吸收影响的研究

目的:考察3种F127/SWCNTs载体系统的稳定性及对小肠P-糖蛋白(P-gp)药泵的抑制作用.方法:将F127/SWC-NTs稀释至不同浓度后于4℃放置15d,检测CNTs含量、粒径、Zeta电位等参数的变化;采用大鼠在体单向灌流模型进行肠吸收试验,以P-gp特异性底物罗丹明123(R-123)大鼠回肠段的吸收速率...     

Preparation and evaluation of icariside II-loaded binary mixed micelles using Solutol HS15 and Pluronic F127 as carriers

An effective anti-cancer drug, icariside II (IS), has been used to treat a variety of cancers in vitro. However, its poor aqueous solubility and permeability lead to low oral bioavailability. The aim of this work was to use Solutol®HS15 and Pluronic F127 as surfactants to develop novel mixed micelles to enhance the oral bioavailability of IS by improving permeability and inhibiting efflux. The IS-loaded mixed micelles were prepared using the method of ethanol thin-film hydration. The physicochemical properties, dissolution property, oral bioavailability of the male SD rats, permeability and efflux of Caco-2 transport models, and gastrointestinal safety of the mixed micelles were evaluated. The optimized IS-loaded mixed micelles showed that at 4:1 ratio of Solutol®HS15 and Pluronic F127, the particle size was 12.88?nm with an acceptable polydispersity index of 0.172. Entrapment efficiency (94.6%) and drug loading (9.7%) contributed to the high solubility (11.7?mg/mL in water) of IS, which increased about 900-fold. The SF-IS mixed micelle release profile showed a better sustained release property than that of IS. In Caco-2 cell monolayer models, the efflux ratio dramatically decreased by 83.5%, and the relative bioavailability of the mixed micelles (AUC_0–∞) compared with that of IS (AUC_0–∞) was 317%, indicating potential for clinical application. In addition, a gastrointestinal safety assay also provided reliable clinical evidence for the safe use of this micelle.     

Formulation and evaluation of new long acting metoprolol tartrate ophthalmic gels

The rationale of the present work is to formulate and evaluate metoprolol tartrate (MT), which is a beta-1 selective adrenergic blocking agent in a new ocular gel delivery system; this is our way and method to increase its contact to the cornea, giving a longer time of drug contact to the eye and slow possible release from the preparation. Metoprolol tartrate is chosen as a candidate for gel formulation because although it has been available for a few years as ophthalmic solutions, it has not been marketed as an ocular gel yet. Two polymers; Carbopol 934 and Pluronic F127 (PF127) were used in two different concentrations in this study. Metoprolol tartrate was used in two concentrations, 0.5% and 1% (w/w). All formulations were exposed to visual examinations, pH measurement, in vitro release, rheological study and differential scanning calorimetry (DSC). Results showed that all formulations were clear, showed pH within the acceptable range suitable to be administered in the eye, and exhibited pseudoplastic flow behavior. DSC results concluded that, MT was compatible with different polymers used. In vitro release results showed that the release rate of metoprolol tartrate from gel preparations decreased as an inverse function of polymer concentration, and the release rate of the drug increased as the initial concentration increased. Intra-ocular pressure (IOP) measurements of rabbit’s eye treated with 1% (w/w) metoprolol tartrate in gel formulations with different concentrations of the polymer were determined. Carbopol 934 gel formulations showed that this polymer extended the duration of pressure reducing effect of MT to more than 5hr when compared with Pluronic F127 gel formulations. The area above the curve (AAC), maximum response, time of maximum response (t_max), and the duration of the drug action were also calculated.