蛇床子有效部位水醇凝胶中蛇床子素体外经皮渗透的评价

以蛇床子有效部位中的主要成分蛇床子素为定量指标对蛇床子水醇凝胶剂的经离体人皮的透皮性能进行了研究，考察了Azone、薄荷醇和土荆芥油三种不同渗透促进剂的作用。实验结果表明含有三种渗透促进剂的处方中药物的稳态流量与对照组比较均有提高，增渗倍数分别为3.10、2.00和1.25。含有Azone、薄荷醇和土荆芥油为渗透促进剂的处方中药物的扩散系数与对照组相比，分别提高为5.54、4.73和2.13倍，但分配系数却分别降低为0.56、0.46和0.59倍。结果提示三种渗透促进剂的作用机理主要为改变角质层的通透性，减低了药物经皮肤渗透的阻力，提高了药物在皮肤角质层的扩散系数。

Study of Sustained Release Phenylpropanolamine Hydrochloride Hydrophilic Matrix Tablets Containing Hydroxypropylmethylcellulose K100M and Carbopol 971P

选用HPMC K100M和卡波普971P为骨架材料，粉末直接压片法制备骨架片，考察释放度，反相高效液相色谱法检测盐酸苯丙醇胺（PPA·HCl）的浓度。释药曲线均符合Higuchi方程（R＞0．98，P＜0．01）。运用正交设计法，以美国市场的PPA·HCl缓释片Acutrim^R为对照，相似因子f2值为指标，筛选获得了最优处方。其工艺重现性合格。研制片在0．1mol·L^-1 HCl,H2O(pH6.5)，磷酸盐缓冲液（PBS）pH5.0,6.8和7.4的介质中，以及在0.1mol·L^-1HCl中释放2h，转移至PBS6．8中释放10h，相对于对照品的f2值为63－74，表明在各介质中两制剂的释药曲线相似。释药影响因素的考察结果表明：在本实验考察的范围内，骨架片在水中的释药速率与HPMC K100M和卡波普971P的用量呈负相关。HPMC K100M和卡波普971P的比例（保持聚合物总用量相同），硬脂酸镁量和骨架片硬度对释药速率无显著性影响。

Paclitaxel Hydrogelator Delays Microtubule Aggregation

Paclitaxel （PTX） is one of the most efficient anticancer drugs for the treatment of cancers through β-tubulin-binding. Our previous work indicated that a PTX-derivative hydrogelator Fmoc-Phe-Phe-Lys（paclitaxel）-Tyr（H2PO3）-OH （1）could promote neuron branching but the underlying mechanism remains unclear. Using tubulin assembly-disassembly assay, in this work, we found that compound 1 obviously delayed more microtubule aggregation than PTX did. Under the catalysis of alkaline phosphatase, Fmoc-Phe-Phe-Lys（paclitaxel）- Tyr（H2PO3）-OH could self-assemble into nanofiber Fmoc-Phe-Phe-Lys（paclitaxel）-Tyr-OH with width comparable to the size of αβ-tubulin dimer. Therefore, we proposed in this work that nanofiber Fmoc-Phe-Phe-Lys（paclitaxel）-Tyr-OH not only inhibits the αβ-tubulin dimer binding to each other but also interferes with the plus end aggregation of microtubule. This work provides a new mechanism of the inhibition of microtubule formation by a PTX- derivative hydrogelator.

The Swelling Equilibria of N-isopropylacrylamide Based Hydrogel in Aqueous Solution of Ethanol

N-isopropylacrylamide (NIPAAm) was used to synthesize NIPAAm homopolymer (nonionized) and NIPAAm-sodium methacrylate copolymer (ionized). The swelling equilibria for both gels were obtained in aqueous solution of ethanol with concentration ranging from 0 to 100%(by mass) at 25℃. The swollen gel in water shrank first with the addition of a small amount of ethanol and then reswelled with further addition of ethanol showing not only a discontinuous volume phase transition but also a typical reentrant phenomenon. A thermodynamic model based on the UNIQUAC with the 'free-volume' contribution was applied to correlate and predict the swelling behavior of the poly(NIPAAM)-gels in ethanol-water mixture.

Application of modified polyethylene glycol hydrogels in the construction of tissue engineered heart valve

To enhance the adhesion of seeding-cells to the biomaterial scaffolds, the PEG-hydrogels were modified. Porcine aortic valves were decellularized with Triton X-100 and trypsin. The cells were encapsulated into the PEG-hydrogels to complete the process of the cells attaching to the acellular porcine aortic valves. Herein, the autologous mesenchymal stem cells （MSCs） of goats were selected as the seeding-cells and the tendency of MSCs toward differentiation was observed when the single semilunar TEHV had been implanted into their abdominal aortas. Furthermore, VEGF, TGF-β1, and the cell adhesive peptide motif RGD were incorporated. Light and electron microscopy observations were performed. Analysis of modified PEG-hydrogels TEHV＇s （PEG-TEHV） tensile strength, and the ratio of reendothelial and mural thrombosis revealed much better improvement than the naked acellular porcine aortic valve （NAPAV）. The data illustrated the critical importance of MSC differentiation into endothelial and myofibroblast for remodeling into native tissue. Our results indicate that it is feasible to reconstruct TEHV efficiently by combining modified PEG-hydrogels with acellular biomaterial scaffold andautologous MSCs cells.

蛇床子素及其制剂的药效学研究

目的研究蛇床子素及其贴剂、凝胶的药效学。方法采用小鼠阴道上皮细胞、大鼠尾部皮肤鳞片表皮颗粒层形成、鸡蛋清所致大鼠足肿胀、巴豆油所致小鼠耳肿胀、组胺致豚鼠皮肤毛细血管通透性增高及磷酸组织胺致痒模型，研究了蛇床子素及其贴剂、凝胶的药效学。结果蛇床子素及其贴剂、凝胶具有抑制小鼠阴道上皮细胞有丝分裂、促进大鼠尾部皮肤鳞片表皮颗粒层形成、抗炎、止痒及减少组胺致豚鼠皮肤毛细血管通透性。结论通过蛇床子素及其贴剂、凝胶药效学研究，表明其对银屑病和湿疹具有一定的治疗作用。

Muscle-inspired ion-sensitive hydrogels with highly tunable mechanical performance for versatile industrial applications

Human muscles are notably toughened or softened with specific inorganic ions.Inspired by this phenomenon,herein we report a simple strategy to endow hydrogels with comparable ion-responsive mechanical properties by treating the gels with different ionic solutions.Semi-crystalline poly(vinyl alcohol)hydrogels are chosen as examples to illustrate this concept.Similar to muscles,the mechanical property of hydrogels demonstrates strong dependence on both the nature and concentration of inorganic ions.Immersed at the same salt concentration,the hydrogels treated with different ionic solutions manifest a broad-range tunability in rigidity(Young’s modulus from 0.16 to 9.6 MPa),extensibility(elongation ratio from 100% to 570%),and toughness(fracture work from 0.82 to 35 MJm^(-3)).The mechanical property well follows the Hofmeister series,where the“salting-out”salts(kosmotropes)have a more pronounced effect on the reinforcement of the hydrogels.Besides,the hydrogels’mechanical performance exhibits a positive correlation with the salt concentration.Furthermore,it is revealed both the polymer solubility from amorphous domains and polymer crystallinity from crystalline domains are significantly influenced by the ions,which synergistically contribute to the salt-responsive mechanical performance.Benefitting from this feature,the hydrogels have demonstrated promising industrial applications,including tunable tough engineering soft materials,anti-icing coatings,and soft electronic devices.

Tunable supramolecular hydrogels from polypeptidePEG-polypeptide triblock copolymers

A series of ABA triblock copolymers of poly(?-(2-methoxy ethoxy)esteryl-glutamate)-block-poly(ethylene glycol)-blockpoly(?-(2-methoxy ethoxy)esteryl-glutamate) with poly(ethylene glycol) as middle hydrophilic B block and oligo(ethylene glycol)-functionalized polyglutamate(poly-L-EG2Glu) as terminal A blocks were prepared via ring-opening polymerization of EG2 Glu N-carboxyanhydride(NCA). The resulting P(EG2Glu)-b-PEG-b-P(EG2Glu) triblocks can spontaneously form hydrogels in water. The intermolecular hydrogen bonding interactions between polypeptides blocks were responsible for the formation of gel network structure. These hydrogels displayed shear-thinning and rapid recovery properties, which endowed them potential application as injectable drug delivery system. The mechanical strength of hydrogels can be modulated by copolymer composition, molecular weight and concentrations. Also, it was found that the hydrogels' strength decreased with temperature due to dehydration of polypeptide segments. Atomic force microscopy and scanning electron microscopy images revealed that these hydrogels were formed through micelle packing mechanism. Circular dichroism and Fourier transform infrared spectroscopy characterizations suggested the poly-L-EG2 Glu block adopted mixed conformation. A preliminary assessment of drug release in vitro demonstrated the hydrogels can offer a sustained release of doxorubicin(DOX) and the release rate could be controlled by varying chemical composition.

Self-healable wire-shaped supercapacitors with two twisted NiCo_2O_4 coated polyvinyl alcohol hydrogel fibers

Wire-shaped supercapacitors（SCs） possessing light-weight, good flexibility and weavability have caught much attention, but it is still a challenge to extend the lifespan of the devices with gradual aging due to the rough usage or external factors. Herein, we report a new stretchable and selfhealable wire-shaped SC. In the typical process, two polyvinyl alcohol/potassium hydroxide（PVA/KOH） hydrogel wrapped with urchin-like NiCo2O4 nanomaterials were twisted together to form a complete SC devices. It is noted that the as-prepared PVA hydrogel can be easily stretched up to 300% with small tensile stress of 12.51 kPa, superior to nearly 350 kPa at 300%strain of the polyurethane. Moreover, the wire-like SCs exhibit excellent electrochemical performance with areal capacitance of 3.88 mF cm^-2 at the current density of 0.053 mA cm^-2, good cycling stability maintaining 88.23% after 1000 charge/discharge cycles, and 82.19% capacitance retention even after four damaging/healing cycles. These results indicate that wireshaped SCs with two twisted NiCo2O4 coated polyvinyl alcohol hydrogel fibers is a promising structure for achieving the goal of high stability and long-life time. This work may provide a new solution for new generation of self-healable and wearable electronic devices.

Vortex fluidic mediated one-step fabrication of polyvinyl alcohol hydrogel films with tunable surface morphologies and enhanced self-healing properties

Previous strategies for controlling the surface morphologies of polyvinyl alcohol(PVA)-based hydrogels,including freeze-drying and electrospinning,require a posttreatment process,which can affect the final textures and properties of the hydrogels.Of particular interest,it is almost impossible to control the surface morphology during the formation of PVA hydrogels using these approaches.The strategy reported in this study used the novel vortex fluidic device(VFD)technology,which for the first time provided an opportunity for one-step fabrication of PVA hydrogel films.PVA hydrogels with different surface morphologies could be readily fabricated using a VFD.By also reducing the crosslinking agent concentration,a self-healing gel with enhanced fracture stress(60%greater than that of traditionally made hydrogel)was achieved.Interestingly,the associated selfhealing property remained unchanged during the 260-s mechanical testing performed with the strain rate of 5%s-1.The VFD can effectively tune the surface morphologies of the PVA-based hydrogels and their associated properties,particularly the self-healing property.