Drug self-assembly: A phenomenon at the nanometer scale with major impact in the structure–biological properties relationship and the treatment of disease

Under water-rich conditions, small amphiphilic and hydrophobic drug molecules self-assemble into supramolecular nanostructures. Thus, substantial modifications in their interaction with cellular structures and the ability to reach intracellular targets could happen. Additionally, drug aggregates could be more toxic than the non-aggregated counterparts, or vice versa. Moreover, since self-aggregation reduces the number of effective “monomeric” molecules that interact with the target, the drug potency could be underestimated. In other cases, the activity could be ascribed to the non-aggregated molecule while it stems from its aggregates. Thus, drug self-assembly could mislead from drug throughput screening assays to advanced preclinical and clinical trials. Finally, aggregates could serve as crystallization nuclei. The impact that this phenomenon has on the biological performance of active compounds, the inconsistent and often controversial nature of the published data and the need for recommendations/guidelines as preamble of more harmonized research protocols to characterize drug self-aggregation were main motivations for this review. First, the key molecular and environmental parameters governing drug self-aggregation, the main drug families for which this phenomenon and the methods used for its characterization are described. Then, promising nanotechnology platforms investigated to prevent/control it towards a more efficient drug development process are briefly discussed.     

Topical delivery of paclitaxel for treatment of skin cancer

Context: Skin cancer represents the most growing types of cancer in human and ultraviolet radiation can be cited as one of the prime factor for its occurrence. Current therapy of skin cancer suffers from numerous side effects; for effective therapy, topical application of formulation of paclitaxel (PTX) can be considered as a novel approach.

Objective: The present study is an attempt to prepare formulation of solid lipid nanoparticles (SLN) of PTX for the effective treatment of various form of skin carcinoma.

Methods: The SLN were prepared by high-speed homogenization and ultrasonication method. The prepared SLN were characterized. The optimized PTX SLN were loaded in carbopol gel. The prepared gels were evaluated for its gelling properties and finally studied for in vivo anti-cancer efficacy and histopathological study.

Results: The particle size distribution was found to be in the range of 78.82–587.8?nm. The product yield (%) was found between 60% and 66% and showed a highest entrapment efficiency of 68.3%. The in vitro release of the drug from SLN dispersion was found to be biphasic with the initial burst effect, followed by slow release. SLN-loaded gel were subjected to permeability study and the results show steady-state flux (J_ss), permeability coefficient (K_p), and enhancement ratio were significantly increased in SLN-loaded gel formulation as compared with PTX-loaded gel. The histopathological study clearly reveals the efficacy of the SLN-F3 3G in the treatment of skin cancer.

Conclusion: The experimental formulations show controlled release of PTX and thus expected to show reduce dose-related side effects.     

EVA-g-GMA的制备及其对PLA/PHBV共混物性能的影响

通过熔融聚合法先制备了乙烯-醋酸乙烯酯接枝甲基丙烯酸缩水甘油酯(EVA-gGMA),采用红外光谱仪和核磁共振对EVA-g-GMA的结构进行了表征。然后将不同质量分数的EVA-g-GMA加入到聚乳酸/聚(3-羟基丁酸酯-co-3-羟基戊酸酯)(PLA/PHBV)共混物中,对共混物的性能进行研究。结果表明:GMA成功接枝到EVA上,随着EVA-g-GMA加入量的增加,PHBV与PLA的Tg升高,结晶度逐渐下降;分散相在PLA基体中的分散逐渐均匀,粒径减小,相界面渐渐模糊;在EVA-g-GMA加入后,共混物粘度升高,断裂伸长率和冲击强度分别可达290.9%和43.5KJ·m-2,三元共混物的水蒸气阻隔性相对于PLA/PHBV略有下降。综合考虑各种因素,EVA-g-GMA的加入使得PLA/PHBV的整体性能得到极大改善。     

燃气热循环下7YSZ热障涂层的微结构演变与阻抗谱特征

在1250℃燃气热循环条件下,测试热障涂层抗冷热冲击性能,以模拟发动机叶片的启动升温与关闭降温循环过程。采用电化学阻抗谱测试和扫描电镜(SEM)系统研究热循环过程中热生长氧化物(TGO)生长与YSZ陶瓷层微结构演变。结果表明:随着热循环次数增加,热障涂层内TGO不断生长变厚,在中频阶段的阻抗谱响应越来越显著。YSZ陶瓷层内部经历了微裂纹的萌生与扩展两个阶段。经过100次热循环后的YSZ层表现出与喷涂态涂层相似的阻抗特征,表明高温下烧结会使YSZ层产生的微裂纹在短时间内愈合。但经过300次热循环后的YSZ层表现出与喷涂态完全不同的阻抗谱,并随热循环次数增加,YSZ颗粒间隙阻抗值不断增加,表明YSZ内层产生了不可愈合的微裂纹,是导致YSZ层最终失效的主要因素。     

Mechanical and thermal properties of RE4Hf3O12 (RE=Ho,Er, Tm) ceramics with defect fluorite structure

The thermal and environmental barrier coatings (T/EBC) are technologically important for advanced propulsion engine system. In this study, RE₄Hf₃O₁₂ (RE=Ho, Er, Tm) with defect fluorite structure was investigated for potential use as top TBC layer. Dense pellets were fabricated via a hot pressing method and the mechanical and thermal properties were characterized. RE₄Hf₃O₁₂ (RE=Ho, Er, Tm) possessed a high Vickers hardness of 11 GPa. The material retained high elastic modulus at elevated temperatures up to 1773 K, which made it attractive for high temperature application. The coefficient of thermal expansion (CTE) of RE₄Hf₃O₁₂ (RE = Ho, Er, Tm) laid in the range between 7 × 10⁻⁶ K⁻¹ to 10 × 10⁻⁶ K⁻¹ from 473 K to 1673 K. In addition, the rare earth hafnates exhibited lower thermal conductivity which rendered it a good candidate material for thermal barrier applications.     

Skin detection for single images using dynamic skin color modeling

Up-to-date skin detection techniques use adaptive skin color modeling to overcome the varying skin color problem. Most methods for tracking skin regions in videos utilize the correlation between contiguous frames. This paper proposes a new approach for detecting skin in a single image. This approach uses a local skin model to shift a globally trained skin model to adapt the final skin model to the current image. Experimental results show that the proposed method can achieve better accuracy. Two improvements for speeding up the processing are also discussed.     

Cross‐talk acceptability in natural still images for different (auto)stereoscopic display technologies

Abstract— One of the most annoying distortions in (auto)stereoscopic displays is probably cross‐talk, visible as double edges, which is mainly caused by an imperfect separation of left‐ and right‐eye images. For different types of three‐dimensional (3‐D) displays, cross‐talk is caused by different origins, which could result in different levels of perceived image distortion. To evaluate the influence of (auto)stereoscopic display technology on cross‐talk perception, optical measurements and subjective assessments were performed with three different types of 3‐D displays. It is shown with natural still images that the 3‐D display technology with the lowest luminance and contrast level tolerates the highest level of cross‐talk, while still maintaining an acceptable image‐quality level.     

Adaptive neural control for an uncertain robotic manipulator with joint space constraints

In this paper, adaptive neural tracking control is proposed for a robotic manipulator with uncertainties in both manipulator dynamics and joint actuator dynamics. The manipulator joints are subject to inequality constraints, i.e., the joint angles are required to remain in some compact sets. Integral barrier Lyapunov functionals (iBLFs) are employed to address the joint space constraints directly without performing an additional mapping to the error space. Neural networks (NNs) are utilised to compensate for the unknown robot dynamics and external force. Adapting parameters are developed to estimate the unknown bounds on NN approximations. By the Lyapunov synthesis, the proposed control can guarantee the semi-global uniform ultimate boundedness of the closed-loop system, and the practical tracking of joint reference trajectory is achieved without the violation of predefined joint space constraints. Simulation results are given to validate the effectiveness of the proposed control scheme.