Structure-function relationship of phase-separated liposomes containing diacylglycerol analogues.

The composition and morphology of lipid-based nanoparticles can influence their overall in vivo behavior. Previously, we demonstrated that phase separation in liposomes composed of DSPC and a diacylglycerol lipid analogue (DOaG) drives the in vivo biodistribution towards a specific subset of endothelial cells in zebrafish embryos. In the absence of traditional targeting functionalities (e.g., antibodies, ligands), this selectivity is mediated solely by the unique liposome morphology and composition, characterized by a DOaG-rich lipid droplet within the DSPC-rich phospholipid bilayer. The phase separation is induced due to the geometry of DOaG lipid and its ability to create non-bilayer phases in lipid membranes. To investigate the underlying principles of phase separation and to optimize the liposome colloidal stability, we performed a structure-function relationship study by synthesizing a library of DOaG analogues with varying molecular properties, such as the number, length and sn-position of the acyl chains, as well as the degree of saturation or carbonyl substituents. We assessed the ability of these lipid analogues to assemble into phase-separated liposomes and studied their morphology, colloidal stability, and in vivo biodistribution in zebrafish embryos. We found that analogues containing unsaturated, medium length (C16-C18) fatty acids were required to obtain colloidally stable, phase-separated liposomes with cell-specific biodistribution patterns. Moreover, we observed that using the pure DOaG isomer, with acyl chains at the sn-1,3 positions, leads to more colloidally stable liposomes than when a mixture of sn-1,2 and sn-1,3 isomers is used. Similarly, we observed that incorporating a DOaG analogue with fatty tails shorter than DSPC, as well as PEGylation, endows liposomes with long term stability while retaining cell-selective biodistribution. Diacylglycerols are known to promote fusion, lipid polymorphism, signaling and protein recruitment on lipid membranes. In this study, we showed that diacylglycerol derivatives can induce phase separation in liposomes, unlocking the potential for cell-specific targeting in vivo. We believe that these findings can be the foundation for future use of diacylglycerols in lipid-based nanomedicines and could lead to the development of novel targeted delivery strategies.

Biological recognition and cellular trafficking of targeted RNA-lipid nanoparticles.

Lipid nanoparticles (LNPs) have unlocked the potential of ribonucleic acid (RNA) therapeutics and vaccines. Production and large-scale manufacturing methods for RNA-LNPs have been established and rapidly accelerate. Despite this, basic research on LNPs is still required, due to their high assembly complexity and fairly new development, including research on lipid organization, transfection optimization, and in vivo behavior. Understanding fundamental aspects of LNPs that is, how lipid composition and physicochemical properties affect their biodistribution, cell recognition, and transfection, could propel their clinical development and facilitate overcoming current challenges. Herein, we review recent developments in the field of LNP technology and summarize the main findings focusing on nano-bio interactions.

Effect of somatotype on the general physical fitness tests and throwing velocity on handball

Abstract Aim: The study aimed to investigate the effects of the somatotype components on handball. Methods: The sample consisted of 60 elite junior handball players. Somatotype was evaluated using the Heath & Carter method. The kinetic performance trials of the handball athletes were running speed performance over 5 m 10 m and 20 m sprints, sit and reach, standing long jump (SLJ), ball velocity, and maximum aerobic power. For the data analyses, we used Pearson correlation and multiple linear regression. Results: The endomorphic component correlated positive with all three sprint times (5 m, 10 m και 30 m sprints) (r = 0.315, p = 0.014; r = 0.367, p = 0.004; r = 0.358, p = 0.005 respectively) while negative with SLJ (r = -0.418, p = 0.001) και maximum aerobic power (r = -0.322, p = 0.012). The mesomorphic component had a positive correlation with ball velocity (r = 0.260, p = 0.045) and negative relation with SLJ (r = -0.261, p = 0.044). The ectomorphic component exhibited a negative correlation only with ball velocity (r = -0.260, p = 0.045). The ordinary least square regression models found that endomorphy and ectomorphy were prognostic factors and predicted worse performance in all of the examined motor performance indices except ball velocity and 5 m sprint, while mesomorphy was a predictor of worse performance in SLJ. Conclusions: In conclusion, according to the findings of this study, somatotype components play an important role in performance-related parameters.