Effects of lipid nanocarriers on the performance of topical vehicles in vivo

Background/aims  Nanocarrier systems have been extensively studied for their suitability in personal care formulations. Theoretically, they could enhance skin delivery of active compounds, thereby improving in vivo efficacy of the products. As such the aim of this study was to evaluate the effect of a lipid nanocarrier (LNC) system loaded with tocopheryl acetate (TA) on the hydration, biomechanical properties, and antioxidant capacity of human skin, when used in two different vehicles, and compare it with a non-LNC formulation.
Methods  TA-loaded lipid nanocarriers (TA-LNCs) were produced by the phase inversion method, using physiological lipids and purified by ultra-centrifugation. They were incorporated into a hydrophilic gel and foam, and their performance compared with a saturated TA solution in silicon oil. Skin hydration and biomechanical properties were measured by means of a corneometer and a cutometer, respectively, while a high-resolution spectrophotometer was used to assess skin redness after stimulation by methyl nicotinate in a micro-inflammatory test. Both short-term (3 h) and long-term trials (4 weeks) were performed.
Results  The results confirmed that the LNCs enhanced skin hydration in both studies, while skin viscoelastic parameters remained practically unchanged during the 4-week study. The antioxidant assessment failed to show significant difference between the test sites.
Conclusions  TA-loaded LNCs exhibited the ability to enhance skin hydration, while their effect on skin biomechanical properties and on antioxidant efficacy could not be statistically proved.     

An Experimental and Theoretical Determination of Oscillatory Shear-Induced Crystallization Processes in Viscoelastic Photonic Crystal Media

A study is presented of the oscillatory shear-ordering dynamics of viscoelastic photonic crystal media, using an optical shear cell. The hard-sphere/“sticky”-shell design of these polymeric composite particles produces athermal, quasi-solid rubbery media, with a characteristic viscoelastic ensemble response to applied shear. Monotonic crystallization processes, as directly measured by the photonic stopband transmission, are tracked as a function of strain amplitude, oscillation frequency, and temperature. A complementary generic spatio-temporal model is developed of crystallization due to shear-dependent interlayer viscosity, giving propagating crystalline fronts with increasing applied strain, and a gradual transition from interparticle disorder to order. The introduction of a competing shear-induced flow degradation process, dependent on the global shear rate, gives solutions with both amplitude and frequency dependence. The extracted crystallization timescales show parametric trends which are in good qualitative agreement with experimental observations.     

Thermal Analysis-Based Field Validation of the Deformation of a Recycled Base Course Made with Innovative Road Binder

The deformation of the cold recycled mixture with foamed bitumen in a recycled base with an innovative three-component road binder and foamed bitumen is analysed. Numerical simulation results for the pavement constructed, based on laboratory test results, were verified against the data from the monitoring system installed on the road trial section. In addition, environmental effects, such as air temperature and humidity levels in the pavement structure layers, were considered. Thermal analyses were conducted to identify the thermal properties of the pavement materials under steady heat transfer rate. Determining temperature distribution in the road cross-section in combination with relaxation functions determined for individual pavement layers contributed to the high effectiveness of the numerical simulation of deformation and displacement in the recycled base and the entire pavement. The experimental method of identifying thermal properties allows a fast and satisfactory prediction of temperature distribution in the pavement cross-section.     

基于流变学指标的后交联祖师麻凝胶贴膏剂混合工艺研究

目的以流变学参数弹性模量(G′)、黏性模量(G″)、屈服应力(τ0)、蠕变柔量[J(t)]及损耗系数(tanδ)作为评价指标,优化祖师麻凝胶贴膏剂(Daphnes Giraldii Cortex gel plaster,DGCGP)混合工艺。方法采用正交设计,选用L_9(3~4)正交试验表,以物料混合时的温度、转速以及混合时间为考察因素,以混合后含药胶料的各项流变学参数为评价指标,筛选出DGCGP最佳的混合工艺,并预测适合的涂布条件。结果优选的DGCGP混合工艺为混合温度70℃,转速10 r/min,时间2 h,在此条件下,混合胶料的黏弹性、耐温耐剪切性、抗变形能力以及稳定性均良好。结论采用优化工艺条件制备的DGCGP外观良好,且质地柔软,黏弹性好,质量较佳。     

炭黑中性墨水的流动曲线及动态黏弹特性

测试了炭黑中性墨水的流变性能,探讨了炭黑中性墨水的流变性能与书写和存储稳定性等应用性能的关系。结果表明,炭黑中性墨水具有显著的剪切变稀特性,用Hersegel Bulkley方程拟合得到的流动指数为0.3~0.6。同时发现日本进口针管型笔头炭黑中性墨水为黏性流体,子弹型笔头炭黑中性墨水为黏弹性流体。跟踪测试存储150 d的炭黑中性墨水的弹性模量(G’) 时间的关系,得到的墨水存储稳定性结论与通过线性黏弹区结构分析得到的稳定性结论一致,表明结构稳定性是中性墨水存储稳定性的关键,可以通过线性黏弹区的特性快速判断中性墨水的存储稳定性。     

Closantel nano-encapsulated polyvinyl alcohol (PVA) solutions

The influence of closantel on the rheological and physicochemical properties (particle size and by UV–Vis absorption spectroscopy) of PVA aqueous solutions is studied here. About 1% PVA aqueous solutions were prepared by varying the closantel content. The increase of closantel content led to a reduction in the particle size of final solutions. All the solutions were buffered at pH?7.4 and exhibited shear-thinning behavior. Furthermore, in oscillatory flow, a “solid-like” type behavior was observed for the sample containing 30?μg/mL closantel. Indicating a strong interaction between the dispersed and continuous phases and evidencing an interconnected network between the nanoparticle and PVA, this sample also showed the highest shear viscosity and higher shear thinning slope, indicating a more intrincate structure disrupted by shear. In conclusion, PVA interacts with closantel in aqueous solution and the critical concentration for closantel encapsulation by PVA was about 30?μg/mL; above this concentration, the average particle size decreased notoriously which was associated to closantel interacting with the surface of the PVA aggregates and thus avoiding to some extent direct polymer–polymer interaction.     

血液粘弹特性的力学模型

本文提出一个由弹性模量为Ｇ的胡克弹簧和粘度为ηＣ（Ｃａｓｓｏｎ粘度）的阻尼器相串联的粘弹体力学模型，并讨论这一模型的粘弹特性：应力松驰、蠕变和动粘弹性。结果表明，这些特性与具有屈服应力的血液的粘弹行为相一致（除蠕变外）。由此现模型可视为血液粘弹特性一个简化的力学模型。本文还探讨了屈服应力与粘弹特性的相互关系。     

Strain-enhanced stress relaxation impacts nonlinear elasticity in collagen gels

The extracellular matrix (ECM) is a complex assembly of structural proteins that provides physical support and biochemical signaling to cells in tissues. The mechanical properties of the ECM have been found to play a key role in regulating cell behaviors such as differentiation and malignancy. Gels formed from ECM protein biopolymers such as collagen or fibrin are commonly used for 3D cell culture models of tissue. One of the most striking features of these gels is that they exhibit nonlinear elasticity, undergoing strain stiffening. However, these gels are also viscoelastic and exhibit stress relaxation, with the resistance of the gel to a deformation relaxing over time. Recent studies have suggested that cells sense and respond to both nonlinear elasticity and viscoelasticity of ECM, yet little is known about the connection between nonlinear elasticity and viscoelasticity. Here, we report that, as strain is increased, not only do biopolymer gels stiffen but they also exhibit faster stress relaxation, reducing the timescale over which elastic energy is dissipated. This effect is not universal to all biological gels and is mediated through weak cross-links. Mechanistically, computational modeling and atomic force microscopy (AFM) indicate that strain-enhanced stress relaxation of collagen gels arises from force-dependent unbinding of weak bonds between collagen fibers. The broader effect of strain-enhanced stress relaxation is to rapidly diminish strain stiffening over time. These results reveal the interplay between nonlinear elasticity and viscoelasticity in collagen gels, and highlight the complexity of the ECM mechanics that are likely sensed through cellular mechanotransduction.The composition and architecture of ECM is heterogeneous and varies with tissue type and location. One particularly important ECM protein is type Ι collagen, which is the most abundant ECM component and primarily determines the mechanics of connective tissue (1). Type 1 collagen self-assembles into fibers, and these fibers can form networks in vitro. Studies investigating the mechanical properties of collagen networks have revealed that these networks are nonlinearly elastic and exhibit strain stiffening, or an increase in the elasticity as the strain on the network is enhanced (1–3). This nonlinear elasticity is also a characteristic feature of fibrin gels, which serve as the major component of blood clots, as well as in reconstituted networks of intermediate filaments and cytoskeletal actin networks (2, 4–7). These networks are all composed of semiflexible polymers or fibers, which are relatively rigid, so that the tangent to the contour of the polymer is correlated over long lengths, yet undergo substantial bending fluctuations due to thermal energy. Semiflexible polymers or fibers form networks at low volume fractions (8). Strain stiffening in these networks is thought to arise from either the entropic elasticity of single polymers resisting extension (entropic model) (2, 5), or from alignment of fibers in the direction of strain with a corresponding transition to a regime of elasticity dominated by fiber stretching at higher strains (nonentropic model) (5, 7, 9, 10). Although it has long been known that cells sense and respond to the elastic modulus of ECMs (11–14), recent work has indicated an impact of nonlinear elasticity as well. Studies have found that the nonlinear elasticity of ECM regulates modes of cell motility (15) and differentiation of mesenchymal stem cells (16), alters how far cells are able to sense into the ECM (17), and enables long-range mechanical signaling between cells (18).In addition to often displaying nonlinear elasticity, most biological gels are viscoelastic and exhibit a time-dependent elastic modulus. These gels undergo stress relaxation in response to an applied strain: the initial stress resisting an applied strain decreases over time due to reorganization processes that relax the stresses in the matrix. In the case of collagen gels typically used for in vitro studies, viscoelasticity and stress relaxation likely arise from unbinding of the weak interactions, such as hydrophobic and electrostatic forces, which hold the fibers in a network (19–21). Interestingly, recent studies have found that viscoelasticity in synthetic hydrogels used as cell culture substrates can influence cell behaviors such as spreading, proliferation, and differentiation (22–25). The nonlinear elasticity of collagen and fibrin is dependent on the history of applied strains, indicating an influence of viscoelasticity on nonlinear elasticity (19). Here, we directly investigate the coupling between viscoelasticity and nonlinear elasticity for various gels, and find that increased strain leads to faster stress relaxation in collagen and fibrin gels. In collagen gels, these results can be explained by force-dependent unbinding of cross-links, and indicate a mechanism whereby strain stiffening is rapidly dissipated.     

高乌甲素凝胶贴膏的流变学研究

目的 利用流变学对高乌甲素凝胶贴膏配方进行研究。方法 利用SMS物性测试仪测定胶强度,初步筛选高乌甲素凝胶贴膏的填充剂,然后利用旋转流变仪考察填充剂的用量和增黏剂对流变学的影响。结果 微粉硅胶增加基质胶强度最好,选作填充剂。流变学测定显示微粉硅胶可增加凝胶贴膏的弹性模量(elastic modulus,G′)和黏性模量(viscous modulus,G″),对前者增加效果更好,最佳含量为2.5%;不同增黏剂均显著增加G″,而PVA对G′影响小,故选作增黏剂。采用中国药典2015年版第四部的黏附性检查法证实优化的高乌甲素凝胶贴膏黏附性能良好。结论 流变学参数是筛选凝胶贴膏处方的一种有用工具。