Synthesis and Characterization of Solution Processable Poly(pyrazolines)

Solution‐processable poly(dibenzalacetone) and poly(dibenzalcyclohexanone) are prepared by the condensation of 1,4‐dialkoxy‐bisbenzaldehyde and acetone/cyclohexanone using classic Claisen–Schmidt condensation. The prepared polymers are readily soluble in common organic solvents due to the presence of alkoxy chains present on the aromatic ring. The availability of α,β‐unsaturated ketone on the backbone is readily functionalized with hydrazine hydrate to obtain poly(pyrazoline acetate), a nonconjugated polymer on the backbone, which shows enhanced emission characteristics on comparison with the pristine polymer and small molecule analogues. The highest occupied molecular orbital–lowest unoccupied molecular orbital (HOMO–LUMO) of levels of poly(pyrazolines) has a band gap of 1.54 eV as calculated from cyclic voltammetry and UV–vis studies. Uniform thin film is obtained by spin casting as 1% solution on chlorobenzene and annealing under vacuum. Atomic force microscopy analysis shows fine morphology of the thin film. I–V characterization of the film shows low turn‐on voltage of 5.3 V. HOMO–LUMO is calculated by density functional theory and the result suggests that these molecules have great potential toward polymer organic light‐emitting diode applications.     

Kinetic Investigations of Quaternization Reactions of Poly[2‐(dimethylamino)ethyl methacrylate] with Diverse Alkyl Halides

Kinetic investigations of the quaternization reactions of poly[2‐(dimethylamino)ethyl methacrylate] (PDMAEMA) with alkyl halides (1‐iodobutane, 1‐iodoheptane, and 1‐iododecane) are carried out at different temperatures. For this purpose, a PDMAEMA (M_n = 17.8 kDa, Ð = 1.35) synthesized via reversible addition fragmentation chain transfer polymerization is utilized. The progress of the quaternization reactions is followed by proton nuclear magnetic resonance. As expected, the rate of quaternization is higher with increasing temperature. The experimental data are used to determine the following kinetic parameters: order of the reaction, Arrhenius' pre‐exponential factor, and activation energy. To the best of knowledge, this is the first contribution that provides detailed kinetic data of the quaternization reactions on PDMAEMA.     

Pressurized IntraPeritoneal Aerosol Chemotherapy with one minute of electrostatic precipitation (ePIPAC) is feasible,but the histological tumor response in peritoneal metastasis is insufficient

IntroductionElectrostatic precipitation Pressurized IntraPeritoneal Aerosol Chemotherapy (ePIPAC) has shown superior penetration depth and tissue uptake compared to standard PIPAC. We investigated the feasibility and objective tumor response to ePIPAC with 1 min of precipitation in patients with peritoneal metastasis (PM).Materials and methodsPatients with PM from various abdominal cancers were included in an amendment to the ongoing prospective PIPAC-OPC2 trial. Colorectal and appendiceal PM were treated with oxaliplatin, patients with PM from other primaries were treated with a combination of cisplatin and doxorubicin. Three ePIPAC procedures were planned in each patient including repeated peritoneal biopsies for response evaluation. After emission to the peritoneal cavity, the aerosolized chemotherapeutics were precipitated for 1 min followed by immediate exsufflation and abdominal closure. Histological regression from the first to the third ePIPAC was evaluated according to the Peritoneal Regression Grading Score (PRGS) and compared to data from the PIPAC-OPC1 trial. Complications and toxicities were recorded according to Dindo-Clavien and CTCAE.ResultsSixty-five ePIPAC procedures were performed in 33 patients (median 2, range 1–6). Ten patients were eligible for response evaluation based on biopsies from the first and third ePIPAC procedure. Four patients had disease progression, four patients had regressive disease, and two patients had stable disease according to PRGS. No life threatening adverse reactions and no mortality was observed following ePIPAC.ConclusionOne minute ePIPAC was feasible and safe, but the histological tumor response was insufficient compared to standard PIPAC directed therapy with 30 min passive diffusion time.     

载As2O3 pH敏感钙砷复合物脂质体的制备及体外评价

目的 制备pH敏感释药的As₂O₃脂质体，并进行体外评价。方法 采用薄膜分散法制备含钙离子脂质体，然后用离子沉淀法孵育制备钙砷复合物脂质体（CaAs-LP）。测定CaAs-LP的粒径、Zeta电位及多分散系数（PDI）；透射电子显微镜观察脂质体的形态；电感耦合等离子体发射光谱仪测定纳米药物的载药量与包封率；透析袋法考察其体外释药特性。噻唑蓝（MTT）法考察未载药脂质体及CaAs-LP对人源性乳腺癌MCF-7细胞、人源性脑胶质瘤U87细胞和人源性肝癌HepG2细胞的毒性；共聚焦显微镜考察U87细胞对CaAs-LP的摄取效率。结果 制备的CaAs-LP呈规整类球型，粒径约为（117.16±1.94）nm，包封率和载药量分别为（74.31±2.11）%、（8.31±0.13）%。体外释放研究表明，CaAs-LP具有明显的缓释以及pH响应释药特征。未载药的脂质体在MCF-7、U87、HepG2和L02细胞中的生物相容性良好；CaAs-LP抑制肿瘤细胞生长的作用较原药有所上升，半数抑制浓度（IC₅₀）值分别为11.91、4.90、19.41、27.59 μmol/L。细胞摄取研究表明肝癌细胞对脂质体具有良好的摄取。结论 CaAs-LP具备显著的缓释以及pH响应释药的特性，在肿瘤治疗方面具有较好的应用前景。     

Preparation,characterization and in vitro activities evaluation of solid lipid nanoparticles based on PEG-40 stearate for antifungal drugs vaginal delivery

The present article reports the preparation, characterization and performance evaluation of solid lipid nanoparticles (SLNs) based on polyoxyethylene-40 stearate (PEG-40 stearate) for the administration of antifungal agents such as ketoconazole and clotrimazole. These nanoparticles could be useful in the treatment of vaginal infections sustained by Candida albicans. In particular, PEG-40 stearate was made to react with acryloyl chloride in order to introduce an easily polymerizable moiety for the creation of a second shell and to ensure a slow drug release. In addition, the differences on the release profiles between PEG-40 stearate-based nanoparticles, PEG-40 stearate acrylate based and polymerized ones, were analyzed under conditions, simulating the typical environment of Candida albicans infection. Then, the antifungal activity of nanoparticles was also evaluated in terms of minimal inhibitory concentration. Moreover, the nanoparticles were submitted to in vitro studies for evaluating the drug permeability at the site of action. Results indicated that the obtained particles are potentially useful for the treatment of vaginal infections sustained by Candida albicans.     

基于响应面法优选美洲大蠊口腔原位温敏凝胶的制备研究

目的制备美洲大蠊Periplaneta americana口腔原位温敏凝胶。方法采用自由基聚合法首次以N-异丙基丙烯酰胺(NNIPAM)和甲基丙烯酸羟丙酯(HPMA)合成聚(N-异丙基丙烯酰胺-甲基丙烯酸羟丙酯)[P(NNIPAM-HPMA)]作为温敏材料;通过冷溶法制备美洲大蠊口腔原位温敏凝胶,采用Box-Behnken设计响应面法,以溶蚀时间、胶凝时间为评价指标,在固定美洲大蠊提取物用量基础上,对羟丙基甲基纤维素(HPMC)、聚乙烯吡咯烷酮(PVP K30)、P(NNIPAM-HPMA)的用量进行优选。结果通过原位聚合法合成了P(NNIPAM-HPMA)温敏材料;并用响应面法优选了可用于口腔的美洲大蠊原位温敏凝胶的处方,优选的处方为美洲大蠊提取物10%、HPMC 3.0%、PVP K30 9.5%、P(NNIPAM-HPMA) 10.0%,其溶蚀时间为2 h,胶凝时间8～9 s。结论优选得到美洲大蠊口腔原位温敏凝胶,为美洲大蠊提取物的口腔原位局部的临床应用奠定了科学依据。     

Nitric oxide producing coating mimicking endothelium function for multifunctional vascular stents

The continuous release of nitric oxide (NO) by the native endothelium of blood vessels plays a substantial role in the cardiovascular physiology, as it influences important pathways of cardiovascular homeostasis, inhibits vascular smooth muscle cell (VSMC) proliferation, inhibits platelet activation and aggregation, and prevents atherosclerosis. In this study, a NO-catalytic bioactive coating that mimics this endothelium functionality was presented as a hemocompatible coating with potential to improve the biocompatibility of vascular stents. The NO-catalytic bioactive coating was obtained by covalent conjugation of 3,3-diselenodipropionic acid (SeDPA) with glutathione peroxidase (GPx)-like catalytic activity to generate NO from S-nitrosothiols (RSNOs) via specific catalytic reaction. The SeDPA was immobilized to an amine bearing plasma polymerized allylamine (PPAam) surface (SeDPA-PPAam). It showed long-term and continuous ability to catalytically decompose endogenous RSNO and generate NO. The generated NO remarkably increased the cGMP synthesis both in platelets and human umbilical artery smooth muscle cells (HUASMCs). The surface exhibited a remarkable suppression of collagen-induced platelet activation and aggregation. It suppressed the adhesion, proliferation and migration of HUASMCs. Additionally, it was found that the NO catalytic surface significantly enhanced human umbilical vein endothelial cell (HUVEC) adhesion, proliferation and migration. The in vivo results indicated that the NO catalytic surface created a favorable microenvironment of competitive growth of HUVECs over HUASMCs for promoting re-endothelialization and reducing restenosis of stents in vivo.     

Ionic (Co)Organocatalyst with (Thio)Urea Anion and Tetra‑n‑butyl Ammonium Cation for the Polymerization of γ‐Butyrolactone

An effective ionic organocatalyst system is developed for the challenging ring‐opening polymerization (ROP) of γ‐butyrolactone (GBL) at low temperature. The catalysts are prepared by dehydration reaction between tetra‐n‐butyl ammonium hydroxide (TBAOH) and (thio)ureas at ambient temperature, and utilized with or without extra benzyl alcohol (BnOH) initiator. The solid‐state structure of TUA‐3 comprising thiourea anion is characterized by X‐ray diffraction analysis. Typically, a mixture of cyclic and linear poly(GBL) with low molecular weights (5000–1600 g mol^?1) and slightly narrow molecular distribution Ð (1.2–1.4) is obtained by single base with/without combination with (thio)ureas. Interestingly, solely linear high‐molecular‐weight poly(GBL) (10 400 g mol^?1) can be achieved by a synergistic effect of TBAOH/N,N′‐isopropylthiourea in the presence of BnOH. The obtained poly(GBL) is characterized with NMR spectroscopy and matrix‐assisted laser desorption/ionization time‐of‐flight mass spectroscopy (MALDI‐TOF MS). Mechanistic studies reveal different polymerization initiation steps in this reported catalyst system, which leads to poly(GBL) with divergent end groups.     

Redox Polymer–Based Nano‐Objects via Polymerization‐Induced Self‐Assembly

Poly(2,2,6,6‐tetramethylpiperidinyloxy‐4‐yl‐methacrylate) (PTMA) redox polymer–based nano‐objects are synthesized by polymerization‐induced self‐assembly with poly[oligo(ethylene glycol) methyl ether methacrylate] and poly[(4‐methacryloyloxy)‐2,2,6,6‐tetramethylpiperidinium chloride] as hydrophilic macro‐chain transfer agents. These hydrophilic blocks are used in order to stabilize hydrophobic PTMA blocks in aqueous medium. The accordingly obtained spherical nano‐objects are observed via transmission electron microscopy analysis. Cyclic voltammetry measurements indicate that the nature and the length of coronal blocks influence the redox process of the PTMA core blocks. Moreover, these electroactive nano‐objects display low viscosities with a shear‐thinning behavior, making them suitable as cathode‐active materials for aqueous flow‐assisted electrochemical systems.