Ketoprofen and MicroRNA-124 Co-loaded poly (lactic-co-glycolic acid) microspheres inhibit progression of Adjuvant-induced arthritis in rats.

Ketoprofen, a non-steroid anti-inflammatory drug, is widely used for relieving the pain and swelling caused by rheumatoid arthritis. However, ketoprofen can't suppress disease progression effectively. In this study, in an effort to improve the therapeutic effect for rheumatoid arthritis (RA), microRNA-124 (miR-124), a promising new therapeutic agent for RA, was co-loaded with ketoprofen into poly (lactic-co-glycolic acid) (PLGA) microspheres and administrated to adjuvant-induced arthritis rats. PLGA microspheres loaded with ketoprofen and miR-124 were prepared by a modified multiple emulsion-solvent evaporation method. In vivo pharmacodynamics experimental results indicated ketoprofen in co-loaded microspheres could significantly reduce inflammation of the joints and miR-124 in the microspheres could reduce bone damage. In addition, ketoprofen and miR-124 co-loaded PLGA microspheres had a remarkable advanced activity over delivery of either miR-124 or ketoprofen in suppressing adjuvant-induced arthritis (AA) in rats. Results of western blot and immunohistochemistry revealed that miR-124 could reduce the level of receptor activator of nuclear factor kappa-B ligand (RANKL). These results suggested co-delivery of ketoprofen and miR-124 could achieve synergistic effects on preventing inflammation and bone damage caused by AA. Ketoprofen and miR-124 co-loaded PLGA microspheres could be a promising combined therapeutic strategy against RA.

Design of hydrogels of 5-hydroxymethyl tolterodine and their studies on pharmacokinetics, pharmacodynamics and transdermal mechanism.

development, single-factor experiments were employed to evaluate the effect of adding different matrix, enhancers, 5-HMT, ethanol and glycerol on drug skin development, single-factor experiments were employed to evaluate the effect of adding different matrix, enhancers, 5-HMT, ethanol and glycerol on drug skin permeation. Finally, Carbopol 940 was selected as the gel matrix with N-methyl pyrrolidone (NMP) chosen as the enhancer. The relationship between time and the steady accumulative percutaneous amount (Q, µgcm-2) of optimized 5-HMT hydrogels was Q4-12h=1290.8t1/2-1227.7. The absolute bioavailability of 5-HMT hydrogels was 20.7% showed in pharmacokinetic study. No skin irritation was observed in 5-HMT hydrogels skin irritation study. In the pharmacodynamic study, the overactive bladder model was induced by 150µg/kg of pilocarpine in rats. The significant effects of 5-HMT hydrogels on the inhibition of urine output on rat model were last to 12h. The optimized 5-HMT hydrogels displayed prolonged pharmacological responses. 5-HMT hydrogels effectively avoided the metabolism difference of enzyme in bodies compared with tolterodine tablets, provided one single active compound in plasma to reduce the variability of having two active compounds. To further elucidate the transdermal mechanism, fourier transform infrared (FTIR) spectroscopy, differential scanning calorimeter (DSC) and activation energy measurements were used to study the transdermal routes and changes of stratum corneum during drug release.