蛇床子素温敏型原位凝胶的研制及含量测定

目的：蛇床子素温敏型凝胶剂的研制,并建立其含量测定方法。方法建立用HPLC法测定制剂的含量及体外释药量。采用搅拌子法测定相变温度并测定其动态黏度,从而确定处方。用转篮法进行处方的体外释放实验。结果确定蛇床子素温敏型凝胶的最佳基质配比是质量分数为25%的泊洛沙姆407和质量分数为10%的泊洛沙姆188的组合。结论该制剂制备工艺简单,进入体内形成凝胶并且24 h累计释放药物约83%。含量测定方法操作简便、快速准确。     

The Preparation and Characterization of Chitosan-Based Hydrogels Cross-Linked by Glyoxal

In this study, hydrogels based on chitosan cross-linked by glyoxal have been investigated for potential medical applications. Hydrogels were loaded with tannic acid at different concentrations. The thermal stability and the polyphenol-releasing rate were determined. For a preliminary assessment of the clinical usefulness of the hydrogels, they were examined for blood compatibility and in the culture of human dental pulp cells (hDPC). The results showed that after immersion in a polyphenol solution, chitosan/glyoxal hydrogels remain nonhemolytic for erythrocytes, and we also did not observe the cytotoxic effect of hydrogels immersed in tannic acid (TA) solutions with different concentration. Tannic acid was successfully released from hydrogels, and its addition improved material thermal stability. Thus, the current findings open the possibility to consider such hydrogels in clinics.     

Comparative Investigation of Collagen-Based Hybrid 3D Structures for Potential Biomedical Applications

Collagen is a key component for devices envisaging biomedical applications; however, current increasing requirements impose the use of multicomponent materials. Here, a series of hybrid collagen-based 3D materials, comprising also poly(ε-caprolactone) (PCL) and different concentrations of hyaluronic acid (HA)—in dense, porous or macroporous form—were characterized in comparison with a commercially available collagen sponge, used as control. Properties, such as water uptake ability, water vapour sorption, drug loading and delivery, were investigated in correlation with the material structural characteristics (composition and morphology). Methylene blue (MB) and curcumin (CU) were used as model drugs. For spongeous matrices, it was evidenced that, in contrast to the control sample, the multicomponent materials favor improved sustained release, the kinetics being controlled by composition and cross-linking degree. The other characteristics were within an acceptable range for the intended purpose of use. The obtained results demonstrate that such materials are promising for future biomedical applications (wound dressings and lab models).     

A Stretchable,Self-Healable Triboelectric Nanogenerator as Electronic Skin for Energy Harvesting and Tactile Sensing

Electronic skin that is deformable, self-healable, and self-powered has high competitiveness for next-generation energy/sense/robotic applications. Herein, we fabricated a stretchable, self-healable triboelectric nanogenerator (SH-TENG) as electronic skin for energy harvesting and tactile sensing. The elongation of SH-TENG can achieve 800% (uniaxial strain) and the SH-TENG can self-heal within 2.5 min. The SH-TENG is based on the single-electrode mode, which is constructed from ion hydrogels with an area of 2 cm × 3 cm, the output of short-circuit transferred charge (Qsc), open-circuit voltage (Voc), and short-circuit current (Isc) reaches ~6 nC, ~22 V, and ~400 nA, and the corresponding output power density is ~2.9 μW × cm⁻² when the matching resistance was ~140 MΩ. As a biomechanical energy harvesting device, the SH-TENG also can drive red light-emitting diodes (LEDs) bulbs. Meanwhile, SH-TENG has shown good sensitivity to low-frequency human touch and can be used as an artificial electronic skin for touch/pressure sensing. This work provides a suitable candidate for the material selection of the hydrogel-based self-powered electronic skin.     

Multiple patterns of polymer gels in microspheres due to the interplay among phase separation,wetting, and gelation

We report the spontaneous patterning of polymer microgels by confining a polymer blend within microspheres. A poly(ethylene glycol) (PEG) and gelatin solution was confined inside water-in-oil (W/O) microdroplets coated with a layer of zwitterionic lipids: dioleoylphosphatidylethanolamine (PE) and dioleoylphosphatidylcholine (PC). The droplet confinement affected the kinetics of the phase separation, wetting, and gelation after a temperature quench, which determined the final microgel pattern. The gelatin-rich phase completely wetted to the PE membrane and formed a hollow microcapsule as a stable state in the PE droplets. Gelation during phase separation varied the relation between the droplet size and thickness of the capsule wall. In the case of the PC droplets, phase separation was completed only for the smaller droplets, wherein the microgel partially wetted the PC membrane and had a hemisphere shape. In addition, the temperature decrease below the gelation point increased the interfacial tension between the PEG/gelatin phases and triggered a dewetting transition. Interestingly, the accompanying shape deformation to minimize the interfacial area was only observed for the smaller PC droplets. The critical size decreased as the gelatin concentration increased, indicating the role of the gel elasticity as an inhibitor of the deformation. Furthermore, variously patterned microgels with spherically asymmetric shapes, such as discs and stars, were produced as kinetically trapped states by regulating the incubation time, polymer composition, and droplet size. These findings demonstrate a way to regulate the complex shapes of microgels using the interplay among phase separation, wetting, and gelation of confined polymer blends in microdroplets.The regulation of the 3D shapes of biopolymer gels at the mesoscale has numerous applications in the biomedical, cosmetic, and food materials industries, among others (1). Recently, top-down and bottom-up approaches have been reported to control the mesoscopic patterns of polymer gels. For example, photolithography and two-photon polymerization allow the regulation of gel patterns at the mesoscale (2–4). The advanced design of the molecules enables polymerization with a self-assembly and produces nonspherical microgels: spherical particles with a cavity, capsules, and cubic particles (5–7). However, these methods require highly specialized equipment and are generally difficult to adapt for biopolymer gels.Dynamical coupling between phase separation and sol–gel transition in polymer blends has also been investigated for the spontaneous formation of spherical microgels and a porous gel (8, 9). Ma et al. (10) and Choi et al. (11) confined aqueous two-phase systems (ATPSs) in microdroplets and fabricated microgels by selective polymerization. In such a confined space, phase separation accompanies wetting of a polymer to the substrate (12–15). Although the selective polymerization of phase-separated polymers in microdroplets has a great potential to produce variously shaped microgels, the dynamical coupling among the phase separation, wetting, and gelation of polymers in a confined space remains unclear (16). If it was better understood, the shapes of polymer microgels could be regulated in a self-organized manner.In the present work, we used gelatin, one of the most popular biopolymer gels, and poly(ethylene glycol) (PEG) as the desolvating agent because PEG leads to phase separation for various biopolymers, such as proteins and DNA (17). The gelatin/PEG solution was confined in water-in-oil (W/O) microdroplets coated by a lipid layer, wherein the phase separation and sol–gel transition of the gelatin occur with a decrease in the temperature (18–20). This process led to gelation after and during the phase separation in the presence of the interactions between the polymers and lipid membranes. We analyzed the pattern formation of the gelatin microgel as a function of the temperature history, droplet size, and polymer composition. We found that variously shaped microgels appeared as stable states and kinetically trapped states. These findings yield a method to regulate the shapes of polymer microgels using the interplay among the interfacial tensions, elastic properties of the gels, and interactions between the polymers and the surfaces of the droplets.     

Crosslinked hydrogels—a promising class of insoluble solid molecular dispersion carriers for enhancing the delivery of poorly soluble drugs

Water-insoluble materials containing amorphous solid dispersions (ASD) are an emerging category of drug carriers which can effectively improve dissolution kinetics and kinetic solubility of poorly soluble drugs. ASDs based on water-insoluble crosslinked hydrogels have unique features in contrast to those based on conventional water-soluble and water-insoluble carriers. For example, solid molecular dispersions of poorly soluble drugs in poly(2-hydroxyethyl methacrylate) (PHEMA) can maintain a high level of supersaturation over a prolonged period of time via a feedback-controlled diffusion mechanism thus avoiding the initial surge of supersaturation followed by a sharp decline in drug concentration typically encountered with ASDs based on water-soluble polymers. The creation of both immediate- and controlled-release ASD dosage forms is also achievable with the PHEMA based hydrogels. So far, ASD systems based on glassy PHEMA have been shown to be very effective in retarding precipitation of amorphous drugs in the solid state to achieve a robust physical stability. This review summarizes recent research efforts in investigating the potential of developing crosslinked PHEMA hydrogels as a promising alternative to conventional water-soluble ASD carriers, and a related finding that the rate of supersaturation generation does affect the kinetic solubility profiles implications to hydrogel based ASDs.KEY WORDS: Amorphous solid dispersions, Crosslinked hydrogels, Poly(2-hydroxyethylmethacrylate), Supersaturation, Kinetic solubility     

Synthesis and Characterization of Thermosensitive Poly(N‐Vinyl Caprolactam)‐Grafted‐Aminated Alginate Hydrogels

Thermosensitive hydrogels are characterized by the drastic and reversible change of their physical properties with temperature. Herein is presented the development of a thermosensitive poly(N‐vinylcaprolactam)‐grafted‐aminated alginate (PNVCL‐g‐Alg‐NH₂) having a temperature‐dependent phase transition close to physiological temperature. The hybrid copolymer is formed through the combinational use of chemical and physical methods, that is, carbodiimide chemistry, and ionotrophic gelation by calcium cations. PNVCL‐g‐Alg‐NH₂ exhibits a phase transition at ≈35 °C, and temperature‐dependent water uptake. Copolymerization with PNVCL leads to a decrease in the water uptake of aminated alginate, while improving its thermal stability. Model protein (bovine serum albumin) release from PNVCL‐g‐Alg‐NH₂ scaffolds indicates a higher rate of release below the lower critical solution temperature (LCST) than that of the above, owing to the fact that PNVCL chains collapse at above the LCST and forms a more compact network. In vitro cytotoxicity and hemocompatibility analyses confirm that PNVCL‐g‐Alg‐NH₂ scaffolds are basically non‐cytotoxic and non‐hemolytic.     

The effects of varying poly(ethylene glycol) hydrogel crosslinking density and the crosslinking mechanism on protein accumulation in three-dimensional hydrogels

Matrix stiffness has been shown to play an important role in modulating various cell fate processes such as differentiation and cell cycle. Given that the stiffness can be easily tuned by varying the crosslinking density, poly(ethylene glycol) (PEG) hydrogels have been widely used as an artificial cell niche. However, little is known about how changes in the hydrogel crosslinking density may affect the accumulation of exogenous growth factors within 3-D hydrogel scaffolds formed by different crosslinking mechanisms. To address such shortcomings, we measured protein diffusivity and accumulation within PEG hydrogels with varying PEG molecular weight, concentration and crosslinking mechanism. We found that protein accumulation increased substantially above a critical mesh size, which was distinct from the protein diffusivity trend, highlighting the importance of using protein accumulation as a parameter to better predict the cell fates in addition to protein diffusivity, a parameter commonly reported by researchers studying protein diffusion in hydrogels. Furthermore, we found that chain-growth-polymerized gels allowed more protein accumulation than step-growth-polymerized gels, which may be the result of network heterogeneity. The strategy used here can help quantify the effects of varying the hydrogel crosslinking density and crosslinking mechanism on protein diffusion in different types of hydrogel. Such tools could be broadly useful for interpreting cellular responses in hydrogels of varying stiffness for various tissue engineering applications.     

新型壳聚糖基引导骨再生膜的蛋白缓释性能研究

目的：制备负载牛血清白蛋白的壳聚糖/β-甘油磷酸钠(CS/β-GP)可吸收性膜,探讨其缓释蛋白的性能。方法：利用CS/β-GP体系的温敏相转变特性,同时向其中添加蛋白制成新型生物膜。进行膜厚度及拉伸强度等力学性能测试。利用BCA蛋白浓度试剂盒（加强型）检测不同时点的蛋白浓度,绘制膜的蛋白缓释曲线。结果：利用SPSS16.0统计分析软件进行分析,负载蛋白后复合膜的理化性能均未发生明显变化（P>0.05）。不同浓度的复合膜可缓慢释放蛋白12天以上,并且随着β-GP浓度的升高,蛋白缓释总量增大。结论：新型壳聚糖温敏凝胶膜可以作为蛋白缓释的载体,是在引导骨再生领域具有应用潜力的生物膜材料。