Drug-eluting coating of ginsenoside Rg1 and Re incorporated poly(lactic-co-glycolic acid) on stainless steel 316L: Physicochemical and drug release analyses.

Active ingredients of ginsenoside, Rg1 and Re, are able to inhibit the proliferation of vascular smooth muscle cells and promote the growth of vascular endothelial cells. These capabilities are of interest for developing a novel drug-eluting stent to potentially solve the current problem of late-stent thrombosis and poor endotheliazation. Therefore, this study was aimed to incorporate ginsenoside into degradable coating of poly(lactic-co-glycolic acid) (PLGA). Drug mixture composed of ginseng extract and 10% to 50% of PLGA (xPLGA/g) was coated on electropolished stainless steel 316L substrate by using a dip coating technique. The coating was characterized principally by using attenuated total reflectance-Fourier transform infrared spectroscopy, scanning electron microscopy and contact angle analysis, while the drug release profile of ginsenosides Rg1 and Re was determined by using mass spectrometry at a one month immersion period. Full and homogenous coating coverage with acceptable wettability was found on the 30PLGA/g specimen. All specimens underwent initial burst release dependent on their composition. The 30PLGA/g and 50PLGA/g specimens demonstrated a controlled drug release profile having a combination of diffusion- and swelling-controlled mechanisms of PLGA. The study suggests that the 30PLGA/g coated specimen expresses an optimum composition which is seen as practicable for developing a controlled release drug-eluting stent.

Identification of the catalytic Mg²âº ion in the hepatitis delta virus ribozyme.

The hepatitis delta virus ribozyme catalyzes an RNA cleavage reaction using a catalytic nucleobase and a divalent metal ion. The catalytic base, C75, serves as a general acid and has a pK(a) shifted toward neutrality. Less is known about the role of metal ions in the mechanism. A recent crystal structure of the precleavage ribozyme identified a Mg²âº ion that interacts through its partial hydration sphere with the G25·U20 reverse wobble. In addition, this Mg²âº ion is in position to directly coordinate the nucleophile, the 2'-hydroxyl of U(-1), suggesting it can serve as a Lewis acid to facilitate deprotonation of the 2'-hydroxyl. To test the role of the active site Mg²âº ion, we replaced the G25·U20 reverse wobble with an isosteric A25·C20 reverse wobble. This change was found to significantly reduce the negative potential at the active site, as supported by electrostatics calculations, suggesting that active site Mg²âº binding could be adversely affected by the mutation. The kinetic analysis and molecular dynamics of the A25·C20 double mutant suggest that this variant stably folds into an active structure. However, pH-rate profiles of the double mutant in the presence of Mg²âº are inverted relative to the profiles for the wild-type ribozyme, suggesting that the A25·C20 double mutant has lost the active site metal ion. Overall, these studies support a model in which the partially hydrated Mg²âº positioned at the G25·U20 reverse wobble is catalytic and could serve as a Lewis acid, a Brønsted base, or both to facilitate deprotonation of the nucleophile.