Merged experimental guided computational strategy toward tuberculosis treatment mediated by alveolar macrophages mannose receptor

Synthesis, Characterizations, and Use of O-Stearoyl Mannose Ligand-Engineered Lipid Nanoarchitectonics for Alveolar Macrophage Targeting

“…The experimental work of screening different ligands in in silico models represented potential properties with OSM. 4 In this study, the envisaged ligand molecule was synthesized by esterification reaction through bond formation between the carboxyl group of stearic acid and the hydroxyl group of mannose. The synthesized product was preliminarily examined by TLC and further confirmed with the characterization tools such as FT-NIR, DSC, and MS, and with CSLM in addition to these.…”

“…The lipid nanoarchitectonics were prepared by using the homogenization technique through stearic acidmediated shell surface and soy lecithin containing core structure of the lipid nanoarchitectonics. The resulted lipid nanoarchitectonics were further incubated with synthesized OSM at room temperature for 48-72 h to attain complete OSM surface impregnation 4 to generate final OSM ligandengineered lipid nanoarchitectonics.…”

“…The lead candidate, O-stearoyl mannose (OSM), was selected. 4 From a formulation point of view, even though the nanoparticles have developed so far to tackle the resident bacterium in macrophages, that is not enough due to lack of site-specific drug delivery and unwanted biodistribution that eventually leads to concurrent frequent dosage regimen, side effects, and reduce patient compliance. 5,6 Nowadays, surface engineering is an emerging field to give more emphasis on site specificity, cargo efficiency, and higher stability.…”

“…[11][12][13] Thereby ligand-mediated active engineering is expected to enhance the rate of particulate accumulations in macrophage significantly. Based on our preliminary exciting in silico experimental results, 4 we have envisioned to the synthesizing the OSM as ligand by conjugating D-(+)-mannose and stearic acid through the esterification process with the reaction mediated by the hydroxyl group of D-(+)-mannose and carboxylic group of stearic acid. In vitro physicochemical characterizations of this synthesized OSM ligand were determined with the usage of preliminary but robust analytical confirmation tools such as chromatography, calorimetry, and spectrometry analysis.…”

Development and validation of UPLC-MS/MS method for in vitro quantitative analysis of pyrazinamide in lipid core-shell nanoarchitectonics for improved metabolic stability

“…A secondary standard was prepared with 20% v/v methanol to attain working standard concentrations of 1.0-200 ng/mL. Nine calibration standards (1,5,10,20,40,80,100,150, and 200 ng/mL) were prepared by further dilution of the secondary standard. The IS was prepared similarly and added to each calibration standard by maintaining the same diluent and a particular part of the volume (%v/v) to attain a final concentration of 5.0 ng/mL.…”