BACKGROUND & AIMS: :Recent studies have shown that keratinocytes can sense temperature via thermo-transient receptor potential (TRP) channels. It is not known whether other thermosensitive ion channels such as TREK-1, TREK-2 and TRAAK (TREKs/TRAAK) that are members of the two-pore domain K(+) (K(2P)) channel family are expressed in human keratinocytes. Here, we identified the expression of TREKs/TRAAK in human keratinocytes-derived cell line HaCaT cells using RT-PCR, immunocytochemistry, Western blot analysis and patch-clamp technique. RT-PCR showed that all six K(2P) channels tested (TASK-1, TASK-3, TREK-1, TREK-2, TRAAK and TASK-2) were expressed in HaCaT cells, as well as in skin and dorsal root ganglion (DRG) of rat. The expression of TREKs/TRAAK mRNA identified by RT-PCR was further studied at the protein level. Using anti-TREK-1, -TREK-2 and -TRAAK, bands of approximately 46, approximately 60 and approximately 43 kDa, respectively, were observed at plasma membrane of HaCaT cells. Immunostaining also showed that TREK-1, TREK-2 and TRAAK were expressed in all area of cells including plasma membrane. Whole-cell K(+) currents recorded from HaCaT cells were activated by arachidonic acid and heat. These results suggest that TREKs/TRAAK channels could act as thermosensors in human keratinocytes.

背景与目标： : 最近的研究表明，角质形成细胞可以通过热瞬时受体电位 (TRP) 通道感知温度。尚不清楚作为两孔结构域K () (K(2P)) 通道家族成员的其他热敏离子通道 (例如TREK-1，TREK-2和TRAAK (TREKs/TRAAK)) 是否在人类角质形成细胞中表达。在这里，我们使用rt-pcr，免疫细胞化学，蛋白质印迹分析和膜片钳技术鉴定了TREKs/TRAAK在人角质形成细胞衍生的细胞系HaCaT细胞中的表达。Rt-pcr显示，所测试的所有六个K(2P) 通道 (TASK-1，TASK-3，TREK-1，TREK-2，TRAAK和TASK-2) 均在HaCaT细胞以及皮肤和大鼠背根神经节 (DRG) 中表达。在蛋白质水平上进一步研究了通过rt-pcr鉴定的TREKs/TRAAK mRNA的表达。使用抗TREK-1，-TREK-2和-TRAAK，在HaCaT细胞的质膜上分别观察到约46，约60和约43 kDa的条带。免疫染色还显示，TREK-1，TREK-2和TRAAK在包括质膜在内的所有细胞区域均表达。花生四烯酸和热激活了从HaCaT细胞记录的全细胞K () 电流。这些结果表明，TREKs/TRAAK通道可以充当人角质形成细胞的热传感器。

BACKGROUND & AIMS: :Thermosensitive hydrogels have been studied as feasible needle-avoidance alternative to vaccine delivery. In this work, we report the development of a new thermal-sensitive hydrogel for intranasal vaccine delivery. This delivery system was formulated with a combination of the polymer Gantrez® AN119 and the surfactant Pluronic® F127 (PF127), with a high biocompatibility, biodegradability and immunoadjuvant properties. Shigella flexneri outer membrane vesicles were used as the antigen model. A stable and easy-to-produce thermosensitive hydrogel which allowed the incorporation of the OMV-antigenic complex was successfully synthetized. A rapid gel formation was achieved at body temperature, which prolonged the OMV-antigens residence time in the nasal cavity of BALB/c mice when compared to intranasal delivery of free-OMVs. In addition, the bacterial antigens showed a fast release profile from the hydrogel in vitro, with a peak at 30 min of incubation at 37 °C. Hydrogels appeared to be non-cytotoxic in the human epithelial HeLa cell line and nose epithelium as well, as indicated by the absence of histopathological features. Immunohistochemical studies revealed that after intranasal administration the OMVs reached the nasal associated lymphoid tissue. These results support the use of here described thermosensitive hydrogels as a potential platform for intranasal vaccination.

背景与目标： : 已经研究了热敏水凝胶作为疫苗递送的可行避免针的替代方法。在这项工作中，我们报告了用于鼻内疫苗递送的新型热敏水凝胶的开发。该输送系统是由聚合物Gantrez的组合配制而成的。®AN119和表面活性剂Pluronic®F127 (PF127)，具有较高的生物相容性、生物降解性和免疫佐剂特性。福氏志贺菌外膜囊泡被用作抗原模型。成功合成了一种稳定且易于生产的热敏水凝胶，该凝胶允许掺入OMV抗原复合物。在体温下实现了快速的凝胶形成，与鼻内递送游离OMV相比，延长了OMV抗原在BALB/c小鼠鼻腔中的停留时间。此外，细菌抗原在体外显示出从水凝胶的快速释放曲线，在37 °C孵育30分钟时达到峰值。水凝胶在人上皮HeLa细胞系和鼻子上皮中似乎也是非细胞毒性的，这由缺乏组织病理学特征所表明。免疫组织化学研究表明，鼻内给药后，omv到达鼻相关淋巴组织。这些结果支持使用此处描述的热敏水凝胶作为鼻内疫苗接种的潜在平台。

BACKGROUND & AIMS: :Oral mucositis (OM) represents a therapeutic challenge frequently encountered in cancer patients undergoing chemotherapy or radiotherapy. Erythropoietin (EPO) has anti-inflammatory, antioxidant, and wound-healing properties and therefore has important roles in the prevention and treatment of OM. In the current study, we developed a thermally sensitive mucoadhesive gel based on trimethyl chitosan (TMC) containing EPO for the treatment of OM. TMCs with various degrees of substitution (DS) were synthesized and mixed with β-glycerophosphate (GP) and characterized for gelation properties by means of rheological analysis. The effects of DS of TMCs and different concentrations of GP on gelation temperature and time were investigated. The mucoadhesive property of the mixtures was also assessed using cattle buccal mucosa. The optimized mixture was loaded with EPO and subjected to in vitro drug release, wash away, in vitro antimicrobial, and wound-healing tests. The effect of EPO-loaded formulation was also investigated in vivo in Sprague-Dawley rats with chemotherapy-induced mucositis. The best properties were obtained with the blend of TMC of 9.8% DS (5%) and GP (20%). EPO was released from the hydrogel during 8 h, and more than 30% of the drug still remained on the mucosa after 3 h of washing the buccal mucosa with phosphate buffer. TMC/GP mixture was characterized by antimicrobial properties. The EPO hydrogel demonstrated in vitro/in vivo wound-healing properties. Therefore, EPO-loaded hydrogel has the potential to be used in the treatment of OM and other oral or subcutaneous wounds.

背景与目标： : 口腔粘膜炎 (OM) 是接受化疗或放疗的癌症患者经常遇到的治疗挑战。促红细胞生成素 (EPO) 具有抗炎，抗氧化和伤口愈合特性，因此在预防和治疗OM中具有重要作用。在当前的研究中，我们开发了一种基于含有EPO的三甲基壳聚糖 (TMC) 的热敏性粘膜粘附凝胶，用于治疗OM。合成了具有不同取代度 (DS) 的tmc，并将其与 β-甘油磷酸 (GP) 混合，并通过流变分析表征了其胶凝性能。研究了TMCs的DS和不同浓度的GP对凝胶化温度和时间的影响。还使用牛颊粘膜评估了混合物的粘膜粘附性能。将优化的混合物负载EPO，并进行体外药物释放，洗净，体外抗菌和伤口愈合测试。还在患有化学疗法诱导的粘膜炎的Sprague-Dawley大鼠体内研究了EPO负载的制剂的作用。用9.8% DS (5%) 和GP (20%) 的TMC的共混物获得最佳性能。EPO在8小时内从水凝胶中释放，并且在用磷酸盐缓冲液洗涤颊粘膜3小时后，超过30% 的药物仍保留在粘膜上。TMC/GP混合物的抗菌特性。EPO水凝胶具有体外/体内伤口愈合特性。因此，装有EPO的水凝胶有可能用于治疗OM和其他口腔或皮下伤口。

BACKGROUND & AIMS: :Cisplatin-based chemo-radiotherapy (RT) is the most effective treatment in patients with loco-regionally advanced nasopharyngeal carcinoma (NPC). However, traditional chemotherapy drugs have low bioavailability and targeting ability, which reduce their antitumor effects. Therefore, we developed a chitosan/ cis-dichlorodiamineplatinum (CS/DDP) hydrogel-based drug delivery system for the in situ treatment of NPC in combination with RT, and investigated their synergistic antitumor efficacy and underlying mechanism of action. CS/DDP hydrogel remarkably prolonged the survival time (81 days) when combined with RT compared to the control group (P < 0.01). The main mechanism was likely the increase in cancer cell apoptosis (76.23 ± 1.13%, p < 0.01). Furthermore, the CS/DDP hydrogel in combination with RT also increased X-ray-induced DSBs and γ-H2AX foci, induced G2/M phase arrest, inhibited cell proliferation by blocking Ki-67, and decreased CD31+ micro-vessel density (MVD). These results underscore the therapeutic potential of the combination of CS/DDP hydrogel and RT for localized NPC.

背景与目标： : 基于顺铂的化学放射疗法 (RT) 是局部区域晚期鼻咽癌 (NPC) 患者最有效的治疗方法。然而，传统的化疗药物具有较低的生物利用度和靶向性，降低了其抗肿瘤作用。因此，我们开发了基于壳聚糖/顺式二氯二胺铂 (CS/DDP) 水凝胶的药物递送系统，用于结合RT原位治疗NPC，并研究了它们的协同抗肿瘤功效和潜在作用机理。与对照组 (p  <  0.01) 相比，CS/DDP水凝胶联合RT显著延长了生存时间 (81  d)。主要机制可能是癌细胞凋亡增加 (76.23   ±   1.13%，p  <  0.01)。此外，CS/DDP水凝胶与RT结合还增加了x射线诱导的DSBs和 γ-H2AX灶，诱导了G2/M期阻滞，通过阻断Ki-67抑制了细胞增殖，并降低了CD31微血管密度 (MVD)。这些结果强调了CS/DDP水凝胶和RT组合对局部NPC的治疗潜力。

BACKGROUND & AIMS: :The purpose of this research is to establish an injectable hydrogel encapsulating copper sulfide (CuS) nanodots for photothermal therapy against cancer. The CuS nanodots were prepared by one-pot synthesis, and the thermosensitive Pluronic F127 was used as the hydrogel matrix. The CuS nanodots and the hydrogel were characterized by morphous, particle size, serum stability, photothermal performance upon repeated 808 nm laser irradiation, and rheology features. The effects of the CuS nanodots and the hydrogel were evaluated qualitatively and quantitatively in 4T1 mouse breast cancer cells. The retention, photothermal efficacy, therapeutic effects, and systemic toxicity of the hydrogel were assessed in tumor bearing mouse model. The CuS nanodots with a diameter of about 8 nm exhibited satisfying serum stability, photoheat conversion ability, and repeated laser exposure stability. The hydrogel encapsulation did not negatively influence the above features of the photothermal agent. The nanodot-loaded hydrogel shows a phase transition at body temperature and, as a result, a long retention in vivo. The photothermal-agent-embedded hydrogel played a promising photothermal therapeutic effect in the tumor bearing mouse model with low systemic toxicity after peritumoral administration.

背景与目标： : 这项研究的目的是建立一种可注射的水凝胶，该水凝胶封装了硫化铜 (CuS) 纳米点，用于光热治疗癌症。通过一锅法合成制备了CuS纳米点，并将热敏Pluronic F127用作水凝胶基质。Cu纳米点和水凝胶的特征在于形态，粒径，血清稳定性，重复808 nm激光照射后的光热性能和流变学特征。定性和定量评估了CuS纳米点和水凝胶在4T1小鼠乳腺癌细胞中的作用。在荷瘤小鼠模型中评估了水凝胶的保留，光热功效，治疗效果和全身毒性。直径约为8 nm的CuS纳米点表现出令人满意的血清稳定性，光热转换能力和重复激光曝光稳定性。水凝胶封装不会对光热剂的上述特征产生负面影响。装有纳米点的水凝胶在体温下显示出相变，因此在体内保留时间长。包埋的光热剂水凝胶在瘤周给药后具有低全身毒性的荷瘤小鼠模型中发挥了有希望的光热治疗作用。

BACKGROUND & AIMS: :Targeted delivery of antitumor drugs triggered by hyperthermia has significant advantages in clinical applications, since it is easy to implement and side effects are reduced. To release drugs site-specifically upon local heating often requires the drugs to be loaded into a thermosensitive polymer matrix with a low critical solution temperature (LCST) between 37 and 42 degrees C. However, the LCSTs of most thermosensitive materials were below 37 degrees C, which limits their application in clinic because they would precipitate once injected into human body and lost thermal targeting function. Herein, we prepared a novel thermosensitive copolymer (poly(N-isopropylacrylamide-co-acrylamide)-b-poly (DL-lactide)) that exhibits no obvious physical change up to 41 degrees C when heated. Docetaxel loaded micelles made of such thermosensitive polymer were prepared by dialysis method and the maximum loading content was found to be up to 27%. The physical properties, such as structure, morphology, and size distribution of the micelles with and without docetaxel were investigated by NMR, X-ray diffraction, dynamic light scattering, atomic force microscopy, etc. The efficacy of this drug delivery system was also evaluated by examining the proliferation inhibiting activity against different cell lines in vitro. After hyperthermia, the cytotoxicity of docetaxel-loaded micelles increased prominently. Our results demonstrated that this copolymer could be an ideal candidate for thermal targeted antitumor drug delivery.

背景与目标： : 热疗引发的抗肿瘤药物的靶向递送在临床应用中具有显着优势，因为它易于实施且副作用减少。为了释放药物，特别是在局部加热时，通常需要将药物装载到具有37至42摄氏度的低临界溶液温度 (LCST) 的热敏聚合物基质中。然而，大多数热敏材料的lcst低于37 ℃，这限制了它们在临床上的应用，因为它们一旦注入人体就会沉淀，失去热靶向功能。本文中，我们制备了一种新型的热敏共聚物 (聚 (N-异丙基丙烯酰胺-共丙烯酰胺)-b-聚 (DL-丙交酯))，当加热时，其在高达41 ℃ 时没有明显的物理变化。通过透析法制备由这种热敏聚合物制成的多西紫杉醇负载胶束，发现最大负载量高达27%。通过NMR，x射线衍射，动态光散射，原子力显微镜等研究了具有和不具有多西紫杉醇的胶束的物理性质，例如结构，形态和尺寸分布。还通过检查体外对不同细胞系的增殖抑制活性来评估该药物递送系统的功效。热疗后，载有多西紫杉醇的胶束的细胞毒性显着增加。我们的结果表明，该共聚物可能是热靶向抗肿瘤药物递送的理想候选者。

BACKGROUND & AIMS: :Poly(N-isopropylacrylamide), PNIPAAm, hydrogels are negatively thermosensitive which means that they have an expanded hydrogel structure at low temperatures and a shrunken structure at high temperatures. Based on this negative thermosensitivity of PNIPAAm, a drug delivery system with PNIPAAm oligomers grafted onto poly(hydroxyethyl methacrylate) PHEMA, a thermally nonresponsive polymer was designed. Poly(hydroxyethyl methacrylate-g-N-isopropylacrylamide), P(HEMA-g-NIPAAm) hydrogels were synthesized to control the release of an imbedded drug. This new grafted system exhibited high diffusivity at temperatures greater than the lower critical solution temperature (LCST) of the PNIPAAm oligomers. Utilizing PNIPAAm's LCST of approximately 34 degrees C, the release rate was controlled by the temperature of the release medium. The LCST of PNIPAAm was tuned by making copolymers with hydrophobic butyl methacrylate (BMA). Theophylline and inulin release profiles were studied using PHEMA, PNIPAAm and P(HEMA-g-NIPAAm) at three temperatures with drug diffusion coefficients determined as a function of temperature and drug type. The molecular weights between crosslinks and mesh sizes of PHEMA hydrogels were calculated using Flory-Rehner and rubber-elasticity theories.

背景与目标： : 聚 (N-异丙基丙烯酰胺)，PNIPAAm，水凝胶是负热敏的，这意味着它们在低温下具有膨胀的水凝胶结构，在高温下具有收缩的结构。基于PNIPAAm的这种负热敏性，设计了一种将PNIPAAm低聚物接枝到聚 (甲基丙烯酸羟乙酯) PHEMA上的药物传递系统，并设计了一种热无响应的聚合物。合成了聚 (甲基丙烯酸羟乙酯-g-N-异丙基丙烯酰胺)，P(HEMA-g-NIPAAm) 水凝胶，以控制嵌入药物的释放。这种新的接枝系统在高于PNIPAAm低聚物的较低临界溶液温度 (LCST) 的温度下表现出高扩散率。利用约34 ℃ 的PNIPAAm的LCST，释放速率由释放介质的温度控制。通过与疏水性甲基丙烯酸丁酯 (BMA) 制备共聚物来调整PNIPAAm的LCST。使用PHEMA，PNIPAAm和P(HEMA-g-NIPAAm) 在三个温度下研究了茶碱和菊粉的释放曲线，并确定了药物扩散系数作为温度和药物类型的函数。使用Flory-Rehner和橡胶弹性理论计算了PHEMA水凝胶的交联和筛孔尺寸之间的分子量。

BACKGROUND & AIMS: UNLABELLED:Abstract Background and Purpose: Topical chemotherapy for urothelial cancer is dependent on adequate contact time of the chemotherapeutic agent with the urothelium. To date, there has not been a reliable method of maintaining this contact for renal or ureteral urothelial carcinoma. We evaluated the safety and feasibility of using a reverse thermosensitive polymer to improve dwell times of mitomycin C (MMC) in the upper tract. MATERIALS AND METHODS:Using a porcine model, four animals were treated ureteroscopically with both upper urinary tracts receiving MMC mixed with iodinated contrast. One additional animal received MMC percutaneously. The treatment side had ureteral outflow blocked with a reverse thermosensitive polymer plug. MMC dwell time was monitored fluoroscopically and intrarenal pressures measured. Two animals were euthanized immediately, and three animals were euthanized 5 days afterward. RESULTS:In control kidneys, drainage occurred at a mean of 5.3±0.58 minutes. Intrarenal pressures stayed fairly stable: 9.7±14.0 cm H20. In treatment kidneys, dwell time was extended to 60 minutes, when the polymer was washed out. Intrarenal pressures in the treatment kidneys peaked at 75.0±14.7 cm H20 and reached steady state at 60 cm H20. Pressures normalized after washout of the polymer with cool saline. Average washout time was 11.8±9.6 minutes. No histopathologic differences were seen between the control and treatment kidneys, or with immediate compared with delayed euthanasia. CONCLUSIONS:A reverse thermosensitive polymer can retain MMC in the upper urinary tract and appears to be safe from our examination of intrarenal pressures and histopathology. This technique may improve the efficacy of topical chemotherapy in the management of upper tract urothelial carcinoma.

背景与目标：

BACKGROUND & AIMS: :The aim of this study was to investigate the physical properties of a chitosan/glycerophosphate (GP) thermosensitive solution which gels at 37 degrees C and evaluate the in vitro release profiles of different model compounds. The gelation rate was dependent on the temperature and on the chitosan deacetylation degree. The solution containing 84%-deacetylated chitosan could be stored 3 months at 4 degrees C without apparent change in viscosity. The in vitro release profiles of the model compounds depended on the presence of GP in the chitosan solution, on their molecular weight and on the presence of lysozyme in the release media. They were not affected by the electrostatic charge of the model compound when present at low concentrations. During the first 4 h, the release was accompanied by a substantial loss of the gel weight which was mainly attributed to the leaching of water and excess GP. Scanning electron micrographs revealed that the solutions yield gels with a highly porous structure after 24 h of exposure to a continuous flow of phosphate buffered saline. These results indicate that the chitosan/GP thermosensitive solutions gel rapidly at body temperature, can remain in the sol state at 4 degrees C and can sustain the delivery of macromolecules.

背景与目标： : 这项研究的目的是研究在37摄氏度下凝胶的壳聚糖/甘油磷酸 (GP) 热敏溶液的物理性质，并评估不同模型化合物的体外释放曲线。胶凝速率取决于温度和壳聚糖脱乙酰度。含有84%-脱乙酰壳聚糖的溶液可以在4 ℃ 下储存3个月，而粘度没有明显变化。模型化合物的体外释放曲线取决于壳聚糖溶液中GP的存在，其分子量以及释放介质中溶菌酶的存在。当它们以低浓度存在时，它们不受模型化合物的静电荷的影响。在最初的4小时内，释放伴随着凝胶重量的大量损失，这主要归因于水和过量GP的浸出。扫描电子显微照片显示，在连续流动的磷酸盐缓冲盐水中暴露24小时后，溶液会产生具有高度多孔结构的凝胶。这些结果表明，壳聚糖/GP热敏溶液在体温下迅速凝胶，在4 ℃ 下可以保持溶胶状态，并可以维持大分子的递送。

BACKGROUND & AIMS: :In situ forming hydrogels based on thermosensitive polymers have attractive properties for tissue engineering. However, the physical interactions in these hydrogels are not strong enough to yield gels with sufficient stability for many of the proposed applications. In this study, additional covalent cross-links were introduced by photopolymerization to improve the mechanical properties and the stability of thermosensitive hydrogels. Methacrylate groups were coupled to the side chains of triblock copolymers (ABA) with thermosensitive poly( N-(2-hydroxypropyl) methacrylamide lactate) A blocks and a hydrophilic poly(ethylene glycol) B block. These polymers exhibit lower critical solution temperature (LCST) behavior in aqueous solution and the cloud point decreased with increasing amounts of methacrylate groups. These methacrylate groups were photopolymerized above the LCST to render covalent cross-links within the hydrophobic domains. The mechanical properties of photopolymerized hydrogels were substantially improved and their stability was prolonged significantly compared to nonphotopolymerized hydrogels. Whereas non-UV-cured gels disintegrated within 2 days at physiological pH and temperature, the photopolymerized gels degraded in 10 to 25 days depending on the degree of cross-linking. To assess biocompatibility, goat mesenchymal stem cells were seeded on the hydrogel surface or encapsulated within the gel and they remained viable as demonstrated by a LIVE/DEAD cell viability/cytotoxicity assay. Expression of alkaline phosphatase and production of collagen I demonstrated the functionality of the mesenchymal stem cells and their ability to differentiate upon encapsulation. Due to the improved mechanical properties, stability, and adequate cytocompatibility, the photopolymerized thermosensitive hydrogels can be regarded as highly potential materials for applications in tissue engineering.

背景与目标： : 基于热敏聚合物的原位形成水凝胶对组织工程具有吸引力。然而，这些水凝胶中的物理相互作用不够强，不足以产生对于许多建议的应用具有足够稳定性的凝胶。在这项研究中，通过光聚合引入了其他共价交联，以改善热敏水凝胶的机械性能和稳定性。甲基丙烯酸酯基团与具有热敏性聚 (N-(2-羟丙基) 甲基丙烯酰胺乳酸酯) A嵌段和亲水性聚 (乙二醇) B嵌段的三嵌段共聚物 (ABA) 的侧链偶联。这些聚合物在水溶液中表现出较低的临界溶液温度 (LCST) 行为，并且随着甲基丙烯酸酯基团数量的增加，浊点降低。这些甲基丙烯酸酯基团在LCST上方进行光聚合，以在疏水结构域中形成共价交联。与非光聚合水凝胶相比，光聚合水凝胶的机械性能得到了显着改善，并且其稳定性得到了显着延长。尽管非UV固化的凝胶在生理pH和温度下在2天内崩解，但光聚合的凝胶在10至25天内降解，具体取决于交联程度。为了评估生物相容性，将山羊间充质干细胞接种在水凝胶表面或封装在凝胶内，如活/死细胞活力/细胞毒性测定所证明，它们保持活力。碱性磷酸酶的表达和胶原蛋白I的产生证明了间充质干细胞的功能及其在包封后分化的能力。由于改进的机械性能，稳定性和足够的细胞相容性，光聚合的热敏水凝胶可被视为在组织工程中应用的极具潜力的材料。

BACKGROUND & AIMS: :The main purpose of this work was to optimize the rheological properties of docetaxel (DCT)-loaded thermosensitive liquid suppositories for rectal administration. DCT-loaded liquid suppositories were prepared by a cold method and characterized in terms of physicochemical and viscoelastic properties. Major formulation parameters including poloxamer (P407) and Tween 80 were optimized to adjust the thermogelling and mucoadhesive properties for rectal administration. Notably, the gel strength and mucoadhesive force significantly increased with the increase in these variables. Furthermore, DCT incorporation did not alter the viscoelastic behavior, and the mean particle size of nanomicelles in it was approximately 16 nm with a distinct spherical shape. The formulation existed as liquid at room temperature and transformed into gel at physiological temperature through the reverse gelation phenomenon. Thus, DCT-loaded thermosensitive liquid suppositories [DCT/P407/P188/Tween 80 (0.25/11/15/10 %)] with optimal gel properties were easy to prepare and administer rectally, and might enable the gel to stay in the rectum without getting out from rectum.

背景与目标： : 这项工作的主要目的是优化用于直肠给药的多西紫杉醇 (DCT) 负载的热敏液体栓剂的流变特性。DCT负载的液体栓剂是通过冷法制备的，并根据理化和粘弹性进行了表征。优化了包括泊洛沙姆 (P407) 和吐温80在内的主要配方参数，以调整直肠给药的热胶凝和粘膜粘附特性。值得注意的是，随着这些变量的增加，凝胶强度和粘膜粘附力显着增加。此外，DCT的掺入不会改变粘弹性行为，并且其中纳米胶粒的平均粒径约为16 nm，具有明显的球形。该制剂在室温下以液体形式存在，并在生理温度下通过反向凝胶现象转化为凝胶。因此，具有最佳凝胶性质的DCT负载的热敏液体栓剂 [DCT/P407/P188/tween80 (0.25/11/15/10%)] 易于制备和直肠施用，并且可能使凝胶能够停留在直肠中而不会从直肠脱出。

BACKGROUND & AIMS: :To characterize the thermal behavior and texture analysis of doxycycline hyclate thermosensitive gels developed for periodontitis treatment containing zinc oxide prepared by using poloxamer (Lutrol(®) F127) as polymeric material and N-methyl pyrrolidone was used as cosolvent. The thermosensitive gel comprising doxycycline hyclate, Lutrol(®) F127, and N-methyl pyrrolidone were characterized for the thermal behavior and texture analysis. The topography of the system after the dissolution test was characterized with scanning electron microscope. Differential scanning calorimetric thermogram exhibited the endothermic peaks in the systems containing high amount of N-methyl pyrrolidone in solvent. The sol-gel transition temperature of the systems decreased as the zinc oxide amount was increased. The addition of doxycycline hyclate, zinc oxide, and N-methyl pyrrolidone affected the syringeability of systems. The addition of zinc oxide into the doxycycline hyclate-Lutrol(®) F127 systems decreased the diameter of inhibition zone against Staphylococcus aureus, Escherichia coli, and Candida albicans since zinc oxide decreased the diffusion and prolonged release of doxycycline hyclate. From scanning electron microscope analysis, the porous surface of 20% w/w Lutrol(®) F127 system was notably different from that of gel comprising doxycycline hyclate which had interconnected pores and smooth surfaces. The number of pores was decreased with increasing zinc oxide and the porous structure was smaller and more compact. Therefore, the addition of zinc oxide could increase the syringeability of doxycycline hyclate-Lutrol(®) F127 system with the temperature dependence. Zinc oxide decreased inhibition zone against test microbes because of prolongation of doxycycline hyclate release and reduced size of continuous cells. Furthermore, zinc oxide also increased the compactness of wall surfaces of Lutrol(®) F127.

背景与目标： : 表征使用泊洛沙姆 (Lutrol (®) F127) 作为聚合物材料，N-甲基吡咯烷酮用作助溶剂。包含盐酸多西环素、Lutrol (®) F127和N-甲基吡咯烷酮被表征用于热行为和质地分析。用扫描电子显微镜表征溶解测试后系统的形貌。差示扫描量热分析图显示了在溶剂中含有大量N-甲基吡咯烷酮的系统中的吸热峰。随着氧化锌量的增加，系统的溶胶-凝胶转变温度降低。盐酸多西环素，氧化锌和N-甲基吡咯烷酮的添加会影响系统的注射器性。氧化锌在盐酸多西环素-Lutrol (®) F127系统减小了对金黄色葡萄球菌，大肠杆菌和白色念珠菌的抑制区直径，因为氧化锌降低了盐酸多西环素的扩散和释放时间。从扫描电子显微镜分析，20% w/w Lutrol的多孔表面 (®) F127系统与包含具有相互连接的孔和光滑表面的多西环素的凝胶明显不同。随着氧化锌的增加，孔的数量减少，多孔结构更小，更致密。因此，添加氧化锌可以增加盐酸多西环素的注射器性 (®) 具有温度依赖性的F127系统。氧化锌减少了对测试微生物的抑制区，这是因为盐酸多西环素释放的延长和连续细胞的尺寸减小。此外，氧化锌还增加了Lutrol壁面的致密性 (®) f127。

BACKGROUND & AIMS: :The objective of this investigation was to develop a thermosensitive vaginal gel containing raltegravir+efavirenz loaded PLGA nanoparticles (RAL+EFV-NPs) for pre-exposure prophylaxis of HIV. RAL+EFV-NPs were fabricated using a modified emulsion-solvent evaporation method and characterized for size and zeta potential. The average size and surface charge of RAL+EFV-NP were 81.8±6.4 nm and -23.18±7.18 mV respectively. The average encapsulation efficiency of raltegravir and efavirenz was 55.5% and 98.2% respectively. Thermosensitive vaginal gel containing RAL+EFV-NPs was successfully prepared using a combination of Pluronic F127 (20% w/v) and Pluronic F68 (1% w/v). Incorporation RAL+EFV-NPs in the gel did not result in nanoparticle aggregation and RAL+EFV-NPs containing gel showed thermogelation at 32.5°C. The RAL+EFV-NPs were evaluated for inhibition of HIV-1(NL4-3) using TZM-bl indicator cells. The EC(90) of RAL+EFV-NPs was lower than raltegravir+efavirenz (RAL+EFV) solution but did not reach significance. Compared to control HeLa cells without any treatment, RAL+EFV-NPs or blank gel were not cytotoxic for 14 days in vitro. The intracellular levels of efavirenz in RAL+EFV-NPs treated HeLa cells were above the EC(90) for 14 days whereas raltegravir intracellular concentrations were eliminated within 6 days. Transwell experiments of NPs-in-gel demonstrated rapid transfer of fluorescent nanoparticles from the gel and uptake in HeLa cells within 30 min. These data demonstrate the potential of antiretroviral NP-embedded vagina gels for long-term vaginal pre-exposure prophylaxis of heterosexual HIV-1 transmission.

背景与目标： : 这项研究的目的是开发一种热敏性阴道凝胶，该凝胶包含雷特格拉韦依非韦伦负载的PLGA纳米颗粒 (RAL efv-nps)，用于预防HIV暴露前。使用改进的乳液-溶剂蒸发方法制备RAL efv-nps，并对尺寸和zeta电位进行了表征。RAL + EFV-NP的平均尺寸和表面电荷分别为81.8 ± 6.4 nm和-23.18 ± 7.18 mV。raltegravir和efavirenz的平均包封效率分别为55.5% 和98.2%。使用Pluronic F127 (20% w/v) 和Pluronic F68 (1% w/v) 的组合成功地制备了含有RAL + EFV-NPs的热敏阴道凝胶。在凝胶中掺入RAL + efv-nps不会导致纳米颗粒聚集，并且含RAL + efv-nps的凝胶在32.5 °C下显示出热凝胶化。使用TZM-bl指示剂细胞评估RAL + EFV-NPs对HIV-1(NL4-3) 的抑制作用。RAL + EFV-NPs的EC(90) 低于雷替格拉韦 + 依非韦伦 (RAL + EFV) 溶液，但没有达到显著性。与未经任何处理的对照HeLa细胞相比，RAL + EFV-NPs或空白凝胶在体外14天内无细胞毒性。RAL + EFV-NPs处理的HeLa细胞中依非韦仑的细胞内水平在14天内高于EC(90)，而raltegravir细胞内浓度在6天内被消除。凝胶中NPs的Transwell实验表明，荧光纳米颗粒在30分钟内从凝胶中快速转移并在HeLa细胞中吸收。这些数据证明了抗逆转录病毒NP包埋的阴道凝胶对长期阴道暴露前预防异性HIV-1传播的潜力。

BACKGROUND & AIMS: :Thermosensitive injectable chitosan hydrogels can be formed by neutralization of acidic chitosan solutions with sodium betaglycerophosphate (Na-β-GP) coupled with increasing temperature to body temperature. Such hydrogels have been considered for applications in bone regeneration. In this study, chitosan hydrogels were enriched with glycerol and the enzyme alkaline phosphatase (ALP) with a view to improving their suitability as materials for bone tissue engineering. Mineral formation was confirmed by infrared spectroscopy (FTIR) and increases in the mass fraction of the hydrogel not consisting of water. Incorporation of ALP in hydrogels followed by incubation in a solution containing calcium ions and glycerophosphate, a substrate for ALP, led to formation of calcium phosphate within the hydrogel. MG-63 osteoblast-like cells were cultivated in eluates from hydrogels containing ALP and without ALP at different dilutions and directly on the hydrogel samples. Hydrogels containing ALP exhibited superior cytocompatibility to ALP-free hydrogels. These results pave the way for the use of glycerol- and ALP-enriched hydrogels in bone regeneration.

背景与目标： : 热敏性可注射壳聚糖水凝胶可以通过用 β 甘油磷酸钠 (Na-β-GP) 中和酸性壳聚糖溶液并增加温度至体温来形成。这种水凝胶已被考虑用于骨再生。在这项研究中，壳聚糖水凝胶富含甘油和碱性磷酸酶 (ALP)，以提高其作为骨组织工程材料的适用性。通过红外光谱 (FTIR) 确认了矿物的形成，并且不包含水的水凝胶的质量分数增加。将ALP掺入水凝胶中，然后在含有钙离子和甘油磷酸 (ALP的底物) 的溶液中孵育，导致在水凝胶中形成磷酸钙。MG-63成骨细胞样细胞在洗脱液中培养，从含有ALP和不含ALP的水凝胶在不同稀释度下，并直接在水凝胶样品上培养。含有ALP的水凝胶显示出优于无ALP水凝胶的细胞相容性。这些结果为在骨再生中使用富含甘油和ALP的水凝胶铺平了道路。

BACKGROUND & AIMS: BACKGROUND:Gene delivery to target cells is crucially important to establish gene therapy and regenerative medicine. Although various virus-based and synthetic molecule-based gene vectors have been developed to date, selective transfection in a site or a cell level is still challenging. For this study, both light-responsive and temperature-responsive synthetic gene vectors were designed for spatiotemporal control of a transfection system. METHODS:11-Mercaptoundecanoic acid-coated gold nanorods were mixed with polyamidoamine dendron-bearing lipids of two types having amino-terminus or ethoxydiethylene glycol-terminus to obtain hybrid vectors. Hybrid vectors were mixed further with pDNA. Then we investigated their physicochemical properties and transfection efficacy with or without near infrared laser irradiation. RESULTS:Hybrid vectors formed complexes with pDNA and exhibited enhanced photothermal property under near infrared laser irradiation compared with parent gold nanorods. Transfection efficacy of complexes was promoted considerably by brief laser irradiation soon after complex application to the cells. Analysis of intracellular distribution revealed that laser irradiation promoted the adsorption of complexes to the cells and cytosolic release of pDNA, which is derived from the change in surface hydrophobicity of complexes through dehydration of temperature-responsive groups. CONCLUSIONS:Hybrid vector is promising as a light-activatable transfection system.

背景与目标：