Background: Desidustat (ZYAN1) is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI) that stimulates erythropoiesis. Stabilizing HIF via PHI is developing as a new therapeutic approach to treat anemia secondary to chronic kidney disease (CKD). This trial evaluated the safety, tolerability, and efficacy of Desidustat in adult CKD patients with anemia, who were not on dialysis. Methods: This was a Phase 2, randomized, double-blind, 6-week, placebo-controlled, dose-ranging, safety and efficacy study. A total of 117 eligible patients were randomized to 4 arms: 100, 150, 200 mg, or placebo. The investigational product was administered every alternate day for 6 weeks in fasting conditions. The primary endpoint was change in hemoglobin (Hb) from baseline to week 6. Results: Baseline demographics were well balanced among all the treatment arms. In the modified intent-to-treat (mITT) population, a mean Hb increase of 1.57, 2.22, and 2.92 g/dL in Desidustat 100, 150, and 200 mg arms, respectively, was observed post 6 weeks treatment. The responder rate (≥1 g/dL increase) was 66% in 100 mg, 75% in 150 mg, and 83% in 200 mg treatment arms, in the mITT population. Eighteen patients had at least one treatment emergent adverse event (TEAE), and 5 patients reported at least one drug-related mild TEAE. No death or serious adverse event was reported during the trial. Conclusion: There was dose-related increase in Hb across all doses compared to placebo in mITT and per-protocol populations. Desidustat also increased pharmacokinetic parameters Cmax and AUC in dose-related manner. There was no significant change in vital signs, electrocardiographic parameters, or safety laboratory values. Clinical Trial Registration Number CTRI/2017/05/008534 (registered on May 11, 2017).

The polysaccharide-based advanced drug delivery system owing to their biocompatibility, ability to encapsulate the drug molecules in their interspaces, and ability to achieve a controlled release of the cargo drug molecules result in improved drug pharmacokinetics. The drug-loaded polysaccharides possess ability to evade the multidrug-resistant microbial efflux pumps by aggregation effect, whereas the drug loaded polysaccharidefabricated metal nanoparticles present an exceptional candidature for effectively transporting the drug molecules across the membrane barriers while enabling the theranostic applications at the same time. The biodegradability of polysaccharide based drug delivery systems ensure a sustained release of the encapsulated drug molecules, which minimizes the side effects caused by a burst release of the cargo therapeutics. These drug delivery systems proved highly beneficial for the NSAIDs that otherwise manifest ulcerogenic effect in the gastrointestinal tract. The large surface area of polysaccharides further provide a higher drug-loading capacity, which maintains the optimal concentration of the cargo drug at the target sites. The emerging applications of biodegradable polysaccharides in the designing of multicompartmental microspheres revolutionized tissue engineering, multi drug delivery, and cell culturing technologies. The present review deals with the current-status of polysaccharides as advanced drug delivery systems.

Incisive search of innovative compounds for regulating pain, inflammation, and bone damage, with nominal side effects has focused on nutritional supplements. The endeavor of this research work was to investigate, for first time, the inhibitory effect of pomegranate rind extract in established models of nociception and inflammation. Pomegranate (50, 100, and 200 mg/kg) and indomethacin (3 mg/kg) was assessed in eddy's hot plate‐induced algesia, carrageenan, and Complete Freund's adjuvant‐induced models in Wistar rats. Results of study conclude that pomegranate at a dose of 200 mg/kg showed significant (p < 0.001) reduction in paw swelling in both inflammatory experimental models. In addition, observations recorded a significant (p < 0.05) increase in nociceptive threshold. Henceforth, we might say that pomegranate (200 mg/kg) decline pain and inflammation by downregulating the activation of TNF‐R1, TNF‐α, IL‐1β, IL‐6, NF‐κB, oxidative stress markers, and tissue histology. Practical applications The research work represents the first report on inhibitory mechanism of NF‐κB by pomegranate rind extract, enriched in tannins and flavanoids. The findings of the study provide satisfactory evidence of pomegranate rind in amelioration of adjuvant‐induced arthritis. Pomegranate rind, being enrich in bioactive compounds like phenolics and flavanoids possess potent antioxidant activity that might contribute in attenuating rheumatoid arthritis.

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