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Background Apremilast (APM) is a novel, orally administered small molecule drug approved for treatment of psoriasis or psoriatic arthritis. Due to its low solubility and permeability, it is classified as a class IV drug according to BCS classification. Dose titration is recommended during APM treatment due to its tolerability and twice-daily dosing regimen issues. Materials and Methods In this study, three different APM-loaded PLGA nanoparticles (F1–F3) were prepared by single emulsion and evaporation method. Based on particle size, PDI, zeta potential (ZP), entrapment efficiency (%EE), drug loading (%DL), and spectral characterization, the nanoparticles (F3) were optimized. The F3 nanoparticles were further evaluated for in vitro release and in vivo pharmacokinetic studies in rats. Results The optimized nanoparticles (F3) had particles size 307.3±8.5 nm with a low PDI value 0.317, ZP of −43.4±2.6 mV, EE of 61.1±1.9% and DL of 1.9±0.1%. The in vitro release profile showed a sustained release pattern of F3 nanoparticles of APM. The pharmacokinetic results showed 2.25 times increase in bio-availability of F3 nanoparticles compared to normal APM suspension. Moreover, significant increase in half-life and mean residence time confirms long-term retention of F3 nanoparticles. Conclusion Bioavailability enhancement along-with long-term retention of the APM-loaded PLGA nanoparticles might be helpful for the once-daily regimen treatment.

Abstract:We investigated the effect of an aqueous extract of Withania somnifera (WS) on insulin sensitivity in non-insulindependent diabetes mellitus (NIDDM) rats. NIDDM was induced by single intraperitoneal injection of streptozotocin (100 mg/kg) to 2 days old rat pups. WS (200 and 400 mg/kg) was administered orally once a day for 5 weeks after the animals were confirmed diabetic (i.e. 75 days after streptozotocin injection). A group of citrate control rats (group I) were also maintained that has received citrate buffer on the second day of their birth. A significant increase in blood glucose, glycosylated haemoglobin (HbA 1 c) and serum insulin levels were observed in NIDDM control rats. Treatment with WS reduced the elevated levels of blood glucose, HbA 1 c and insulin in the NIDDM rats. An oral glucose tolerance test was also performed in the same groups, in which we found a significant improvement in glucose tolerance in the rats treated with WS. The insulin sensitivity was assessed for both peripheral insulin resistance and hepatic insulin resistance. WS treatment significantly improved insulin sensitivity index ( K ITT ) that was significantly decreased in NIDDM control rats. There was significant rise in homeostasis model assessment of insulin resistance (HOMA-R) in NIDDM control rats whereas WS treatment significantly prevented the rise in HOMA-R in NIDDM-treated rats. Our data suggest that aqueous extract of WS normalizes hyperglycemia in NIDDM rats by improving insulin sensitivity.

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