A Pilot First-in-Human Study of Embrace,a Polyethylene Glycol-Based Liquid Embolic Agent,in the Embolization of Malignant and Benign Hypervascular Tumors

PurposeTo investigate the safety and efficacy of an aqueous polyethylene glycol-based liquid embolic agent, Embrace Hydrogel Embolic System (HES), in the treatment of benign and malignant hypervascular tumors.Materials and MethodsA prospective, single-arm, multicenter study included 8 patients, 5 males and 3 females, with a median age of 58.5 years (30–85 years), who underwent embolization in 8 tumors between October 2019 and May 2020. Technical success was defined as successful delivery of HES to the index vessel, with disappearance of >90% of the targeted vascular enhancement or, for portal vein embolization, occlusion of the portal branches to the liver segments for future resection. The volume of HES administered, ease of use (5 point Likert scale), administration time, and adverse events (AEs) were recorded. Evaluation was performed at 7, 30, and 90 days via clinical assessment and blood testing, and follow-up imaging was performed at 30 days.ResultsEight patients were enrolled, and 10 embolizations were performed in 8 lesions. Tumors included hepatocellular carcinoma (n = 4), renal angiomyolipoma (n = 3), and intrahepatic cholangiocarcinoma (n = 1). Technical success was 100%, and the average ease of use was 3.3 ± 1.0 SD. The HES delivery time was 1–28 minutes (median, 16.5 minutes), and the HES volume injected was 0.4–4.0 mL (median, 1.3 mL). All patients reached 30-day follow-up with imaging, and 6 patients reached 90-day follow-up. There were 3 serious AEs in 2 patients that were unrelated to the embolic agent.ConclusionHES resulted in a 100% embolization technical success rate. The product ease of use was acceptable, and no target vessel recanalization was noted on follow-up imaging at 30 days.     

番泻叶、聚乙二醇和二甲基硅油联合应用对胶囊内镜检查可见度及检出率的影响

目的探讨番泻叶、聚乙二醇和二甲基硅油联合应用对于胶囊内镜(CE)检查可见度及检出率的影响。方法选取该院2016年6月-2018年9月拟行CE检查的患者126例,采用随机数表法分为对照组(n=62)与观察组(n=64),两组检查前禁食3 d,对照组予以聚乙二醇和二甲基硅油作为肠道准备,观察组在此基础上给予口服番泻叶。比较两组胃排空时间、小肠转运时间、胃和小肠的染色节段长度、绿色条带长度、肠道清洁程度、两组病变检出情况及不良反应发生情况。结果两组患者胃排空时间、小肠转运时间、胃和小肠的染色节段无明显差异(P0.05);观察组全小肠和远端小肠绿色条带长度短于对照组,差异均有统计学意义[(5.53±2.93) vs (6.74±2.76)cm;t=2.39,P=0.019;(3.37±2.04) vs (5.56±2.13)cm;t=5.90,P=0.000];两组近端小肠清洁程度差异无统计学意义(P0.05),观察组远端小肠(89.06%vs59.68%,χ2=14.35,P=0.000)和全小肠(87.50%vs 48.39%,χ2=22.23,P=0.000)清洁率明显高于对照组,差异有统计学意义;观察组病变总检出率明显高于对照组(92.18%vs 72.58%,χ2=8.40,P=0.004);两组不良反应发生率差异无统计学意义(17.74%vs 18.75%,P0.05)。结论添加番泻叶可有效提高聚乙二醇和二甲基硅油对于CE的检查可见度和检出率。     

Femoral Head Penetration Rates of Second-Generation Sequentially Annealed Highly Cross-Linked Polyethylene at Minimum Five Years

Background

Highly cross-linked polyethylene (HXLPE) liners in total hip arthroplasty (THA) have demonstrated decreased wear rates, resilience to cup orientation, and reduced osteolysis compared to conventional polyethylene. Sequential irradiation and annealing below the melting temperature is unique compared to most HXLPE which is irradiated and remelted. This study purpose is to provide minimum 5-year femoral head penetration rates of sequentially annealed HXLPE in primary THA.

载紫杉醇的大黄酸偶联物纳米胶束的制备及初步评价

目的制备载紫杉醇的D-α-生育酚聚乙二醇1000琥珀酸酯(D-α-tocopheryl polyethylene glycol 1000 succinate,TPGS)修饰的羧甲基壳聚糖-大黄酸偶联物(PTX/TPGS-CR)纳米胶束,并对其进行初步评价。方法采用透析法,以载药量、包封率及粒径为指标,通过单因素考察优化PTX/TPGS-CR纳米胶束的制备工艺并进行验证。以溶血实验及血管刺激性实验初步考察PTX/TPGS-CR纳米胶束的安全性。四甲基偶氮唑盐微量酶反应比色法(MTT)法考察PTX/TPGS-CR纳米胶束对Hela细胞的毒性。通过激光扫描共聚焦显微镜定性和流式细胞仪定量考察Hela细胞对PTX/TPGS-CR纳米胶束的摄取情况。结果制备工艺优化后制得的PTX/TPGS-CR纳米胶束粒径为(197.3±4.4)nm,PDI为(0.131±0.021),电位为(-31.8±0.5)mV,载药量为(48.20±3.03)%,包封率为(87.26±4.91)%。溶血实验结果表明,其溶血率低于1.71%;血管静脉注射无明显刺激性。其对Hela细胞的杀伤作用具有浓度和时间依赖性,能被Hela细胞高效摄取。结论PTX/TPGS-CR纳米胶束载药量和包封率高,安全性好,其体外抗肿瘤活性稍优于Taxol?。     

Study of Silica‐Supported Chromocene Catalysts for Ethylene Polymerization

Ultrahigh molecular weight polyethylene (UHMWPE) has drawn great interest from researchers because it possesses many excellent properties such as superb strength and impact resistance, which other polyolefin cannot achieve. A silica‐supported chromocene catalyst, for the production of UHMWPE, is successfully developed. The polyethylene (PE) produced by the chromocene catalyst can achieve a molecular weight (MW) of over 3 × 10⁶ g mol^?1 with narrow molecular weight distribution (MWD) a value of approximately three. The activity calculated by Cr per unit reaches the maximum when the loading of Cr is 1.7 wt%. With the increasing loading of chromocene, the MW shows a small increase and the MWD becomes narrower. The chromocene catalyst for ethylene polymerization also shows a significant hydrogen response. With 0.01 MPa hydrogen added into the ethylene polymerization, the MW of the PE decreases immensely to only 0.7 × 10⁶ g mol^?1 and the MWD is broadened from <3 to ≈12. If the amount of hydrogen increases, the MW continues to decrease and the MWD becomes wider. The MW of the PE produced by the chromocene catalyst can be regulated easily by adjusting the amount of hydrogen.     

Understanding the Influence of Nanocarrier-Mediated Brain Delivery on Therapeutic Performance Through Pharmacokinetic-Pharmacodynamic Modeling

This study aimed at evaluating how encapsulation in a regular nanocarrier (NC) (providing extended circulation time) or in a brain-targeting NC (providing prolonged circulation time and increased brain uptake) may influence the therapeutic index compared with the unformulated drug and to explore the key parameters affecting therapeutic performance using a model-based approach. Pharmacokinetic (PK) models were built with chosen PK parameters. For a scenario where central effect depends on area under the unbound brain concentration curve and peripheral toxicity relates to peak unbound plasma concentration, dose-effect and drug-side effect curves were constructed, and the therapeutic index was evaluated. Regular NC improved the therapeutic index compared with the unformulated drug due to reduced peripheral toxicity, while brain-targeting NC enhanced the therapeutic index by lowering peripheral toxicity and increasing central effect. Decreasing drug release rate or systemic clearance of NC with drug still encapsulated could increase the therapeutic index. Also, a drug with shorter half-life would therapeutically benefit more from a NC encapsulation. This work provides insights into how a NC for brain delivery should be optimized to maximize the therapeutic performance and is helpful to predict if and to what extent a drug with certain PK properties would obtain therapeutic benefit from nanoencapsulation.     

Screening of Polymer-Based Drug Delivery Vehicles Targeting Folate Receptors in Triple-Negative Breast Cancer

PurposeTo compare cellular uptake and cytotoxicity of fluorescein (FL)-labeled polyethylene glycols (PEGs) carrying 2 folate groups (targeted delivery vehicles [TDVs]) to non-PEGylated molecules with 1 or 2 folate groups.Materials and MethodsThree PEGylated TDVs and 2 non-PEGylated folic acid (FA)–fluorescein (FL) conjugates (FA-FL and FA-FL-FA) were synthesized. Two triple-negative breast cancer cell lines (MDA-MB-231and MDA-MB-468) were cultured to 70% confluency and incubated for 2 h in a folate-depleted medium. Folate receptor (FR) expression was confirmed by immunocytochemistry. Cellular uptake and cytotoxicity of compounds were measured by flow cytometry. Intracellular localization was confirmed using confocal microscopy.ResultsMDA-MB-231 demonstrated 40% more FR staining than MD-MB-468. Intracellular localization of the 2 non-PEGylated molecules (FA-FL and FA-FL-FA) and the 3 PEGylated TDVs was confirmed with confocal microscopy. Cellular uptake was independent of concentration for FA-FL, but there was 26.8% more cytotoxicity at 30 μg/mL compared with no treatment (P ≤ .05). Uptake was > 90% for FA-FL-FA at 10 μg/mL and 30 μg/mL without significant cytotoxicity (P ≤ .005). Cellular uptake was > 80% for all TDVs. The molecule containing monodispersed PEG with M_n = 1,000 g/mol had the highest uptake in both cell lines without cytotoxicity. Maximum toxicity was demonstrated by the molecule containing PEG_2,000 only at the highest dose of 30 μg/mL (8.66% ± 3.94% cytotoxicity; cut-off was 20%).ConclusionsThe molecule containing monodispersed PEG with M_n = 1,000 g/mol and 2 FA targeting groups demonstrated better targetability and cellular uptake as a TDV.     

A novel technique using hydrophilic polymers to promote axonal fusion

The management of traumatic peripheral nerve injury remains a considerable concern for clinicians. With minimal innovations in surgical technique and a limited number of specialists trained to treat peripheral nerve injury, outcomes of surgical intervention have been unpredictable. The inability to manipulate the pathophysiology of nerve injury (i.e., Wallerian degeneration) has left scientists and clinicians depending on the slow and lengthy process of axonal regeneration (~1 mm/day). When axons are severed, the endings undergo calcium-mediated plasmalemmal sealing, which limits the ability of the axon to be primarily re-paired. Polythethylene glycol (PEG) in combination with a bioengineered process overcomes the inability to fuse axons. The mechanism for PEG axonal fusion is not clearly understood, but multiple studies have shown that a providing a calcium-free environment is essential to the process known as PEG fusion. The proposed mechanism is PEG-induced lipid bilayer fusion by removing the hydration barrier surrounding the axolemma and reducing the activation energy required for membrane fusion to occur. This review highlights PEG fusion, its past and current studies, and future directions in PEG fusion.