Optimization of Aquaporin Loading for Performance Enhancement of Aquaporin-Based Biomimetic Thin-Film Composite Membranes

The aquaporin-based biomimetic thin-film composite membrane (ABM-TFC) has demonstrated superior separation performance and achieved successful commercialization. The larger-scale production of the ABM membrane requires an appropriate balance between the performance and manufacturing cost. This study has systematically investigated the effects of proteoliposome concentration, protein-to-lipid ratio, as well as the additive on the separation performance of ABM for the purpose of finding the optimal preparation conditions for the ABM from the perspective of industrial production. Although increasing the proteoliposome concentration or protein-to-lipid ratio within a certain range could significantly enhance the water permeability of ABMs by increasing the loading of aquaporins in the selective layer, the enhancement effect was marginal or even compromised beyond an optimal point. Alternatively, adding cholesterol in the proteoliposome could further enhance the water flux of the ABM membrane, with minor effects on the salt rejection. The optimized ABM not only achieved a nearly doubled water flux with unchanged salt rejection compared to the control, but also demonstrated satisfactory filtration stability within a wide range of operation temperatures. This study provides a practical strategy for the optimization of ABM-TFC membranes to fit within the scheme of industrial-scale production.

Hyperhomocysteinemia Is Associated With Lipid Profiles and Lipid Ratio in Patients With Coronary Artery Disease

Objective: This study aimed to investigate the correlation of Hyperhomocysteinemia (HHcy) or serum homocysteine (Hcy) levels with lipid levels and lipid ratios in individuals with coronary artery disease(CAD).Methods: A total of 1646 subjects with suspected CAD were divided into CAD or control groups. Serum Hcy, total cholesterol(TC), triglycerides(TGs), high-density lipoprotein cholesterol(HDL-C), low-density lipoprotein cholesterol(LDL-C), apolipoprotein(Apo)AI and ApoB concentrations were detected.Results: Serum TC, LDL-C and ApoB in control subjects with HHcy were lower than those in individuals with normal Hcy, and serum HDL-C and ApoAI in CAD subjects with HHcy were lower than those in individuals with normal Hcy(P < 0.05). The correlation analysis showed that serum TGs, LDL-C, ApoAI and HDL-C were correlated with Hcy(P <0.05). There are different HHcy trends affecting the ratios of TC/HDL-C and LDL/HDL-C between the CAD and controls(Pinteraction for TC/HDL-C=0.025; Pinteraction for LDL/HDL-C=0.033). CAD patients with HHcy had a higher ratio of TC/HDL-C(P=0.022) and LDL/HDL-C(P=0.045) than those with normal Hcy, but in the controls, the subjects with HHcy exhibited a trend toward a decreased ratio of TC/HDL-C(P=0.481) and LDL/HDL-C(P=0.303).Conclusion: HHcy was related to the atherogenic lipid profile in patients with CAD. The lipid ratio is more suitable for assessing the effect of HHcy on CAD.

Interaction of cationic antiseptics with cardiolipin-containing model bacterial membranes

Plasma membrane is one of the major targets for cationic antiseptics (CA). The study was aimed to assess molecular effects of CAs of different chemical classes on cardiolipin-containing regions of bacterial plasma membranes. The study was carried out using coarse-grained molecular modeling. Interaction of CAs, such as miramistin, chlorhexidine, picloxidine, and octenidine, with cardiolipin-containing bilayer was assessed based on the CA coarse-grained models. CAs reduced lipid lateral diffusion coefficients and increased the membrane area per lipid. All CAs, except miramistin, reduced the lipid fatty acid chain order parameters. Adding octenidine at a CA : lipid ratio of 1 : 4 resulted in cardiolipin clustering with subsequent pulling the neutral phosphatidylethanolamine molecules out of the model bilayer. It was found that CАs have the potential for sorption to lipid bilayer, causing clustering of negatively charged lipids. Antiseptic octenidine causes formation of cardiolipin microdomains. Abnormal lateral lipid distribution together with pulling out phosphatidylethanolamine molecules can result in increased lipid bilayer permeability. The most significant reduction of cardiolipin lateral diffusion coefficient by 2.8 ± 0.4 times was observed in the presence of CA chlorhexidine at an antiseptic : lipid ratio of 1 : 4.

Data Mining and Machine Learning Approaches in Designing Optimum Drug Delivery Systems: A Prototype Study of Niosomes

This study aims to model the prediction of two clinically relevant properties of drug delivery systems specifically for niosomes, i.e., particle size and drug entrapment efficiency (EE%) using a combined approach of data mining, artificial neural networks (ANN), and design of experiments (DoE). Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) system was adopted to screen published literature on niosomes that resulted in 17 articles with 114 formulations. Eleven properties (input parameters) related to drugs and niosomes affecting particle size and drug entrapment (EE%) (output variables) were precisely identified and used for the network training. The network architecture consists of 5 fully connected hidden layers with eleven hidden nodes in each layer, input layer has eleven nodes where each of these nodes maintains omnidirectional injective relation with the corresponding hidden node. The hyperbolic tangent sigmoid transfer function (HTSTF) with Levenberg-Marquardt backpropagation (LMB) was used to train the model. The network showed the highest prediction accuracy of 93.76% and 91.79% for EE% and particle size prediction. Sensitivity analysis identified drug/lipid ratio and Cholesterol/Surfactant ratio as the most significant factors affecting EE% and particle size of niosomes. Accordingly, nine Donepezil hydrochloride (DNPZ) noisome batches were prepared using a 3x3 factorial design with drug/lipid ratio and cholesterol/surfactant ratio as factors to validate the developed model for a new drug. The model was able to reach a prediction accuracy of more than 97% for experimental batches. Finally, the superiority of global ANN was demonstrated compared to the local RSM model for DNPZ niosome formulations. In conclusion, this study has demonstrated the use of the data mining approach to group published scattered information and formulate a data set to train the ANN that can help to design an optimum formulation and processing parameters for a clinically viable medicine with minimum time, cost, and efforts. However, the key challenge in forming an efficient ANN lies in having a suitable large data set and using the correct algorithm for the network.

Supercritical Assisted Production of Lutein-Loaded Liposomes and Modelling of Drug Release

In this work, a lipophilic ophthalmic drug, lutein, has been entrapped in liposomes, using a supercritical assisted process. Effects of pressure, temperature, and drug to lipid ratio variation were studied on mean diameters and lutein encapsulation efficiency. Liposomes with diameters between 153 ± 38 and 267 ± 56 nm were produced, and lutein encapsulation efficiencies between 86.5 ± 0.4% and 97.8 ± 1.2% were obtained. A Scanning Electron Microscope confirmed spherical shape and mean dimensions of vesicles. The variation of temperature for the production of liposomes showed a significant impact on lutein retention time in the double lipidic layer. Lutein drug release from liposomes produced at 35 °C ended in almost 4.5 days; whereas, liposomes produced at 40 °C showed a faster lutein release in 3 days; then, vesicles obtained at 45 °C released their lutein content in only 2 days. Drug release raw data were well-fitted using Weibull model (R2 up to 99%).

Association of serum adenosine deaminase level with atherosclerotic index in type 2 diabetes mellitus patients

Introduction and Aim:The atherosclerosis is the major cause of morbidity and mortality among diabetes population. Diabetes mellitus can accelerate atherosclerotic processes. Adenosine deaminase (ADA) plays a significant role in both glucose and lipid metabolism through adenosine. This study aimed to correlate the atherosclerotic index with adenosine deaminase levels in Type 2 diabetes mellitus patients. The aim of the study is to find the association between serum ADA levels with atherosclerotic index. Materials and Methods: A cross sectional study conducted in 100 subjects (50 control and 50 T2DM patients). The following biochemical parameter were estimated:total cholesterol, triacylglycerol, HDL- C and ADA. VLDL, LDL and other atherosclerotic index were calculated using formulae. Statistical analysis such as Student’s‘t’ test and Pearson’s correlation were performed. Results: We found significant increase (p value <0.001) in lipid profile, Non-HDL-C and lipid ratio when compared to T2DM with control group. The correlation of serum ADA with lipid profile and lipid ratio didnot show any correlation. Conclusion: Serum ADA used as a biomarker for evaluation of glycemic status. ADA was insignificant, when correlated with dyslipidemia and atherosclerotic index.

Lipid Dynamics in Diisobutylene-Maleic Acid (DIBMA) Lipid Particles in Presence of Sensory Rhodopsin II

Amphiphilic diisobutylene/maleic acid (DIBMA) copolymers extract lipid-encased membrane proteins from lipid bilayers in a detergent-free manner, yielding nanosized, discoidal DIBMA lipid particles (DIBMALPs). Depending on the DIBMA/lipid ratio, the size of DIBMALPs can be broadly varied which makes them suitable for the incorporation of proteins of different sizes. Here, we examine the influence of the DIBMALP sizes and the presence of protein on the dynamics of encased lipids. As shown by a set of biophysical methods, the stability of DIBMALPs remains unaffected at different DIBMA/lipid ratios. Coarse-grained molecular dynamics simulations confirm the formation of viable DIBMALPs with an overall size of up to 35 nm. Electron paramagnetic resonance spectroscopy of nitroxides located at the 5th, 12th or 16th carbon atom positions in phosphatidylcholine-based spin labels reveals that the dynamics of enclosed lipids are not altered by the DIBMALP size. The presence of the membrane protein sensory rhodopsin II from Natronomonas pharaonis (NpSRII) results in a slight increase in the lipid dynamics compared to empty DIBMALPs. The light-induced photocycle shows full functionality of DIBMALPs-embedded NpSRII and a significant effect of the protein-to-lipid ratio during preparation on the NpSRII dynamics. This study indicates a possible expansion of the applicability of the DIBMALP technology on studies of membrane protein–protein interaction and oligomerization in a constraining environment.