Significance: Thrombosis constitutes a major contributor to the global disease burden. Recently, the contribution of neutrophils and neutrophil extracellular traps in thrombosis has been intensively documented. DNAse-I by its ability to cleave DNA has been proposed as an efficient antithrombotic drug. In this paper, we showed that DNase-I inhibits the formation of a platelet thrombus and the generation of fibrin independent of its enzymatic activity on DNA. We proposed that DNase-I hydrolyzes adenosine triphosphate and adenosine diphosphate (two important platelet and neutrophil agonists) into adenosine, an antagonist of platelet and neutrophil.
Our research focuses on evaluating the preliminary stability of solid lipid nanoparticles (SLNs) in order to identify an optimal formulation for studying the skin penetration of SLNs loaded with sesamol, with a view to developing potential cosmetic applications. For this study, SLNs were prepared with varying lipid and surfactant compositions and produced through homogenization and ultrasonication. The particle size (PS), polydispersity index (PDI), zeta potential (ZP), and encapsulation efficiency (EE) were analyzed for the different formulations. We identified OP2Se as the optimal formulation for skin penetration assessment due to its stable PS, PDI, ZP, and EE over time, with a Turbiscan Stability Index (TSI) below 1 after a month, indicating favorable stability conditions. The in vitro skin permeation study compared sesamol-loaded SLNs with a control sesamol hydrogel, revealing controlled release characteristics ideal for localized skin effects without significant bloodstream penetration, attributed to the SLNs’ 200 nm particle size. Further exploration could enhance skin retention and targeting, potentially extending penetration studies and reducing particle size to improve accumulation in hair follicles. Exploring SLN applications beyond sesamol, such as incorporating mineral filters for suncare, offers promising avenues, underscoring SLNs’ versatility in cosmetic formulations and skincare applications.
This study presents a methodological framework for optimizing “blank” solid lipid nanoparticles (SLNs), focusing on the use of a design of experiments (DOE) approach. Rather than emphasizing the applications of SLNs, the objective is to identify and optimize critical formulation and process parameters—specifically those influencing particle size (PS), polydispersity index (PDI), and zeta potential (ZP)—during early development stages. A non-classical mixed design was applied using AZURAD® software (version 4.4.1), incorporating a mixture variable for lipid composition (comprising carnauba wax, glyceryl behenate, glyceryl distearate), and two quantitative factors: the percentage of polysorbate 80 (P80) in the P80/sorbitan oleate surfactant system and ultrasound (US) treatment time. The DOE analysis identified P80 concentration as a key parameter, with optimal formulations observed when P80 ranged between 35% and 45%. A fixed P80 ratio of 41% and a US time of 7.5 min enabled precise adjustment of lipid composition. Following a desirability function analysis, an optimized formulation was obtained with a PS of 176.3 ± 2.78 nm, a PDI of 0.268 ± 0.022, and a ZP of −35.5 ± 0.36 mV. These findings validate the relevance of our DOE-based strategy, offering a scalable, cost-effective platform that reduces material use, time, and analytical effort in SLN development.