Abstract
We have synthesized lipidic prodrugs of celecoxib by grafting aliphatic chains to celecoxib through acyl sulfonamide (1), aryl sulfonyl carbamate (2) and aryl sulfonyl urea (3) chemical linkages. Their molecular formulas were confirmed through HR-MS and the formation of ester bond by FTIR and NMR spectroscopy. Nanoparticles of the different prodrugs 1-3 were successfully formulated using emulsion evaporation method and DSPE-PEG2000 as the only excipient. All nanoparticles depicted size between 130 and 160 nm, PdI ≤0.2 and negative zeta potential values from −25 to −35 mV. In addition, they were stable upon storage at 4 °C and/or at room temperature for about a month (in shelf). Morphology of all nanoparticles were spherical-type as observed in transmission electron microscopy (TEM) and scanning electron microscopy (SEM). The encapsulation efficiency of the prodrug was as high as 99% for all three corresponding prodrugs NPs. The nanoscale prodrugs 1–3, are reported for the first time. Moreover, all the characterization data (physicochemical and biological) regarding NPs are also unique. In addition, all prodrug nanoparticles have preserved in vitro anti-inflammatory activity when incubated with the THP-1 cell line activated with lipopolysaccharide (LPS). In vivo studies on a collagen induced arthritis murine model showed results: Prodrug 3 NPs showed activity but were not as efficient as celecoxib in its free form, this might be due to no or very slow release of celecoxib from the prodrug 3 NPs. To promote the reduction of inflammation using NPs would require to explore the possible administration (in vivo) of other prodrugs 1 and 2 NPs in the future.
Published Version
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call