Controlling degradation of acid-hydrolyzable pluronic hydrogels by physical entrapment of poly(lactic acid-co-glycolic acid) microspheres

Chemically crosslinked biodegradable hydrogels based on di-acrylated Pluronic F-127 tri-block copolymer were prepared by a photopolymerization method. Poly(lactic acid-co-glycolic acid) (PLGA) microspheres were physically entrapped within the Pluronic hydrogel in order to modulate the local pH environment by acidic degradation by-products of PLGA microspheres. The PLGA microspheres were slowly degraded to create an acidic microenvironment, which facilitated the cleavage of an acid-labile ester-linkage in the biodegradable Pluronic hydrogel network. The presence of PLGA microspheres accelerated the degradation of the Pluronic hydrogel and enhanced the protein release rate when protein was loaded in the hydrogel.SEM image of photo-crosslinked Pluronic hydrogel entrapping PLGA microspheres.     

PEO-PPO嵌段聚醚的聚集行为及其在药物载体领域的应用

聚氧乙烯-聚氧丙烯(PEO-PPO)嵌段聚醚是一类非离子型高分子表面活性剂,其结构具有很多独特之处:分子结构具有丰富的可设计性,强烈的温度依赖的胶束化行为以及溶剂选择的多样性,这些都极大丰富了其在溶液中自组装形成聚集体的研究内容。本文结合本课题组的工作着重综述了近期国内外有关线型和支状PEO-PPO嵌段聚醚在水溶液中聚集特性的研究进展,以及酸/碱、无机盐、醇类、小分子表面活性剂和聚合物等添加剂对其聚集行为的影响。PEO-PPO嵌段聚醚具有良好的生物相容性,在水溶液中能形成以PPO链段为疏水内核, PEO链段为亲水外壳的胶束结构,该结构非常适于作为疏水药物的载体。因此本文还综述了此类嵌段聚醚作为药物载体方面的研究成果,期望为药物剂型的开发研究提供理论支持。     

Temperature/pH‐Sensitive Hydrogels Prepared from Pluronic Copolymers End‐Capped with Carboxylic Acid Groups via an Oligolactide Spacer

The Pluronic F127 triblock copolymer was end‐capped by carboxyl groups using a degradable oligolactide as a spacer to confer pH‐ and thermo‐sensitive properties. With increasing chain length of the oligolactide, the temperature‐dependent sol‐gel transition curve was significantly shifted to higher concentration with concomitant narrowing of the gelation temperature range. Carboxylic acid end‐capped Pluronic also exhibited a peculiar pH‐dependent sol‐gel transition behavior. At 37 °C, sharp gel‐to‐sol and sol‐to‐gel transitions were observed around pH = 4.8 and 8.2, respectively. The pH‐dependent phase transition was caused by introduction of carboxylic acid groups at the ends of Pluronic F127.

     

二元Pluronic嵌段共聚物相互作用

用I2探针增溶分光光度法考察二元Pluronic两亲嵌段共聚物在水溶液中的胶束化行为,实验结果表明,对于分子PPO嵌段长度相近的P94/L92和F108/L92二元混合体系,这些分子在全部浓度比例范围内都发生相互作用,生成了混合胶束,由于这些分子的PEO嵌段长度不等,随着具有较短PEO嵌段的L92分子加入,P94/L92和F108/L92混合胶束外壳的EO基团数减少导致水化度降低。对于分子PPO嵌段长度不等的P94/L64二元混合体系,当溶液体当中L64的质量分数wL64<0.4时,由于P94/L64混合预胶束的形成,使P94分子在较高浓度时才生成单组分胶束,当wL64>0.4后,溶液中生成了P94/L64混合胶束,温度升高促进了胶束化行为。     

芘在Pluronic两亲嵌段共聚物胶团中的增溶

用稳态荧光法研究芘在Ｐｌｕｒｏｎｉｃ两亲嵌段共聚物胶团水溶液中的增溶,结果表明共聚物分子中的ＰＰＯ实际含量越大,越有利于Ｐｙ的增容,加入无机盐ＫＣｌ导致生成了表面较少水化的较大胶团,并且由于ＫＣｌ解离产生的离子使溶剂极性增加,这些因素促进了Ｐｙ的增溶。     

Micellar ordered structure effects on high‐resolution CE‐SSCP using Pluronic triblock copolymer blends

Pluronic F108 block copolymers have shown a great promise to achieve the desirable high resolution in the conformation‐sensitive separation of ssDNA using CE‐SSCP. However, fundamental understanding of the structures and properties of Pluronic matrix affecting the resolution is still limited. Unlike conventional gel‐forming homopolymers, Pluronic F108 block copolymers are amphiphilic macromolecules consisting of poly(ethylene oxide)‐b‐poly(propylene oxide)‐b‐poly(ethylene oxide) triblock copolymers, which are capable of forming a highly ordered micellar structure in aqueous solution. In this study, we have performed a series of experiments by blending different types of Pluronic polymers to control the formation of micelles and to study the correlation between separation and rheological characteristics of Pluronic gels affecting the resolution of CE‐SSCP. Our experiments have been specifically designed to elucidate how the micellar structure affects the resolution of CE‐SSCP upon altering the size uniformity and constituent homogeneity of the micelles. Our results suggest that uniformly sized micelle packing is the primary structural feature of Pluronic gel matrix for the high‐resolution separation, while the size and constituent of the micelle themselves need to be considered as secondary factors.     

Mixed micelle formation with hydrophobic and hydrophilic Pluronic block copolymers: implications for controlled and targeted drug delivery

Pluronic block copolymers offer affluent phase behavioral characteristics and are extensively investigated for drug delivery applications. Hydrophobic Pluronics produce larger aggregates whereas hydrophilic Pluronics often generate small-sized micelles in aqueous milieu. To overcome the limitations and combine the advantages of different kinds of Pluronics the mixing of such two types of Pluronics is studied here, especially for hydrophobic Pluronic L81 and relatively hydrophilic Pluronic P123. Critical micelle concentration (CMC) of the developed binary mixtures was 0.032 mg/ml as evidenced from pyrene fluorescence spectroscopy and is located in between that of the individual Pluronics. Dynamic light scattering (DLS) showed very small particle sizes (～20 nm) and low polydispersity indices for most of the mixed micelles. Transmission electron microscopy (TEM) demonstrated spherical shape of micelles. Based upon the ratio of hydrophobic and hydrophilic Pluronics, dispersions of varied stability were obtained. With 0.1/1.0 wt.% and 0.5/3.0 wt.% of Pluronic L81/P123, stable dispersions were obtained. Stability was assessed from turbidity measurement, size analysis and clarity of dispersion on standing. Micelles were also found to be stable in bovine serum albumin (BSA) solution. Mixed micelles showed fairly high entrapment efficiency, loading capacity and sustained release profile for aceclofenac (Acl), a model hydrophobe. Presence of salt lowered Acl solubilization in micelles. Thermodynamic parameters for Acl solubilization in mixed micelles revealed high partition coefficient values and spontaneity of drug solubilization. Thus, the developed novel mixed micelles hold promise in controlled and targeted drug delivery owing to their very small size, high entrapment efficiency and stability.