“Development of multifunctional mesoporous silica nanoparticles with antioxidant properties for treating inflammatory-related diseases"

Multifunctional silica mesoporous nanoparticles for treating inflammatory- related diseases Post-traumatic stress disorder (PTSD) is a long-lasting debilitating condition that impacts a wide range of people across the world, and it is characterized by different kind of symptoms, like re-experiencing the traumatic event, avoidance of trauma-related stimuli, negative thoughts or emotions associated with the traumatic event, general changes in mood and cognition, and hyperarousal symptoms. In addition to the severe psychological issues, a lot of studies have discovered a connection between PTSD and an increased risk of serious physical diseases, which are all known to have an inflammatory component. This inflammatory component is also found in skin infection since the immune system fights it by stimulating inflammation in both the injured tissue and the body. Generally, Staphylococcus aureus is the leading cause of skin and soft tissue infections (SSTI), and the burden of diseases from S. aureus SSTI, particularly those caused by methicillin-resistant isolates (MRSA), is extremely high. To reduce this inflammation state, the aim of this project was to create a natural polymer-based nanocarrier system for the delivery of antioxidant extracts as an innovative approach to target and reduce inflammation. To do that, the “Layer by Layer” technique was used to build a polyelectrolyte multilayer that could encapsulate antioxidant. Two natural polymers, Pectin (PEC) and Chitosan (CH) were alternately used to coat mesoporous silica nanoparticles (MNPs) exploiting their opposite charge to create electrical interactions. Chitosan and Pectin were chosen to be used respectively as polycation and polyanion after the measurement of their Zeta Potential using the Dynamic Light Scattering (DLS), (PE -39 mV and CH +40 mV). Due to the negative charge of the MNPs’ surface, the first layer was the Chitosan, then the Pectin and so on to reach 5 total layers. The anti-inflammatory component was obtained using antioxidants extracted from seaweed. Through the optimization of several extraction parameters such as temperature (°C), time (min) and liquid/solid ratio (mg/mL), carried out thanks to the design of experiment (DOEs), it was possible to optimize an ultrasound assisted extraction using a 50% ethanol solution for 6 different types of seaweed. To evaluate the total phenolic content (TPC), the Folin-Ciocalteu reagent was used: the seaweed extract with the highest TPC was chosen and it was mixed with the Pectin at two different ratios (Antioxidant Extract:Pectin 4:1 and 10:1). Furthermore, the FTIR/ATR was used to detect the presence of different functional groups. Finally, to characterize the MNPs chemistry and morphology, different analyses were performed, such as the TEM, the XPS and the FTIR analyses. To test the cytocompatibility of the MNPs, Live&Dead and PrestoBlue assays were used on primary neo fibroblasts, while the antioxidant activity of the MNPs was tested performing ROS test.