A novel pregabalin functionalized salicylaldehyde derivative loaded mesoporous silica nano scaffold: a prospective carrier for targeting inflammatory cytokine storm

Active pharmaceutical ingredients (APIs) have poor efficacy and low bloodstream and target site concentrations due to their limited water solubility. Pregabalin is essential product to control pain and inflammation. We have synthesized novel pregabalin derivative called gabsali ((S, E)-3-(((2-hydroxybenzylidene)amino)methyl)-5-methylhexanoic acid. We have synthesized it by using salicylaldehyde to functionalize pregabalin (PG). The research was divided into two parts. The first part of the process was making a new kind of pregabalin called gabsali (GS). Second, MSNs were created using the sol-gel technique and then the synthesized GS was added to them. This study introduces a unique drug delivery method that improves bioavailability, stability, and anti-inflammatory activity by incorporating chemically modified pregabalin (GS) into engineered MSNs. This strategy has not been documented in the literature before. Zeta sizer, scanning electron microscopy (SEM), transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), BET analysis, and high-performance liquid chromatography (HPLC) were some of the modern tools used to determine particle size, shape, drug release, and compatibility. Under all tested conditions, the inclusion compound showed a considerable improvement in dissolving rate relative to the crystalline medicine in in vitro dissolving assays. The produced MSNs had a particle size of about 500 nm and were nano-sized, spherical. The FTIR spectroscopy was used to examine the chemical GS. The medicine was successfully added into blank MSNs, resulting in a decrease in both their specific surface area (602.5 ± 0.7 m²/g) and pore width (5.9 nm). In order to identify the potential benefits of GS, this study evaluated a preclinical model of inflammation that was created using ovalbumin (OVA). In a comparison to pregabalin, its anti-inflammatory activity was tested at doses of 50, 75, and 100 mg/kg. Using reverse transcription-polymerase chain reaction (RT-PCR), the levels of inflammatory mediators (cytokines IL-2 and IL-6) in the blood were measured and discovered to be significantly reduced. Cell viability was evaluated using the MTT assay, which showed a higher IC50 compared to pregabalin, the unmodified medicine. According to in vivo pharmacokinetic studies, MSN-GS significantly increased bioavailability compared to the pure drug. Using MSN-GS, the aforementioned results clearly show biocompatibility, improved in-vivo bioavailability, and satisfactory in-vitro performance.