Application of Plackett-Burman design for screening of factors affecting pitavastatin nanoparticle formulation development.

INTRODUCTION: Nanoparticle formulation of pitavastatin calcium is a potential alternative to solve the solubility related problem. However, the formulation of nanoparticle involves various parameters that affect product quality. Plackett-Burman design could facilitate an economical experimental plan that focuses on determining the relative significance of many. AIM: The objective of this study was to screen the variables which could significantly affect the pitavastatin nanoparticle formulation. MATERIALS AND METHODS: The pitavastatin nanoparticles were formulated by preparing nanosuspension using the emulsion solvent evaporation technique followed by freeze-drying. A Plackett-Burman screening design methodology was employed in which seven factors at two levels were tested at 12 runs to study the effect of formulation and process variables on particle size and polydispersity index of nanoparticles. The surface morphology and crystalline nature of nanoparticle were also evaluated. RESULTS: The particle size and polydispersity index of nanosuspension was found in the range of 113.1 to 768.5 nm and 0.068 to 0.508, respectively. Statistical analysis of various variables revealed that stabilizer concentration, injection flow rate, and stirring rate were the most influential factors affecting the particle size and polydispersity index of the formulation. X-ray diffraction (XRD) and scanning electron microscopy (SEM) study suggested the amorphous nature of nanoparticles. CONCLUSIONS: This study concluded that the Plackett-Burman design was an efficient tool for screening the process and formulation variables affecting the properties of pitavastatin nanoparticles and also for the identification of the most prominent factor.

In Silico Discovery of Novel Phytoconstituents of Amyris pinnata as a Mitotic Spindle Kinase Inhibitor.

BACKGROUND: Despite many successes in the discovery of numerous cancer chemotherapeutic agents from natural sources, some of the moieties were dropped because of its inefficiency or serious toxicity. Mitosis is an ordered series of fundamentally mechanical events in which identical copies of the genome are moved to two discrete locations within the dividing cell. The crucial role of the mitotic spindle in cell division has identified, which is an important target in cancer chemotherapy. In the present study, we are reporting molecular docking studies and in silico pharmacokinetic profiles of selected phytoconstituents obtained from Amyris pinnata. METHODS: Molecular docking studies of selected phytoconstituents were performed using iGEMDOCK. The crystal structure of the protein was exported from the protein data bank (PDB id: 4C4H). In silico pharmacokinetic profile of selected phytoconstituents was performed using the SWISSADME server. RESULTS: Compound AMNP6 showed higher binding affinity as compared to the standard ligand. All the selected phytoconstituents have passed the Lipinski rule of five and shown no violations. CONCLUSION: Good binding affinity and drug likeliness of the AMNP6 suggest that it can be further investigated and explored as mitotic spindle kinase inhibitor in cancer disease.

Antimalarial Phytochemicals Identification from Euphorbia Hirta against Plasmepsin Protease: an In Silico Approach.

BACKGROUND: Aspartic protease found in plasmodium parasites such as plasmepsin I, II and IV plays an important role in the degradation of hemoglobin. The studies have shown that effective drug must be able to inhibit more than one type of plasmepsin to avoid further growth of parasites and to prevent resistance of drug. Therefore, plasmepsins are believed to be excellent drug target for malarial disease. Extract of the plant Euphorbia hirta has been proved to exert antimalarial activity. However, molecular mechanism of this activity was not described. AIM: The aim of present investigation is to identify antimalarial phytochemicals of Euphorbia hirta as plasmepsin protease inhibitors using an in silico approach. MATERIALS AND METHODS: Docking studies were performed on three different protein targets plasmepsin I, II, and IV using iGEMDOCK. ADME and bioactivity predictions were done using molinspiration online tool. Toxicity studies were performed using ProTox-II online tool. RESULTS: In the docking studies seven compounds showed significant inhibitory activity with low docking score as compared to standard drug artemisinin. Six compounds showed no violations as per Lipinski rule. Bioactivity prediction states that all the compounds may act through enzyme inhibition. The results of in silico studies suggest that out of the eleven selected phytochemicals isorhamnetin and pinocembrin have more drug likeliness properties and lesser in silico toxicity with more binding affinity than artemisinin on all receptors. CONCLUSION: These findings indicate that isorhamnetin and pinocembrin have promising potential for development of antimalarial drug as plasmepsin inhibitors.

Protective effect of simvastatin and rosuvastatin on trinitrobenzene sulfonic acid-induced colitis in rats.

OBJECTIVE: Statins have anti-inflammatory effects that are not directly related to their cholesterol lowering activity. This study was carried out to evaluate the effect of simvastatin or rosuvastatin on the extent of colonic mucosal damage and on the inflammatory response in trinitrobenzene sulfonic acid (TNBS)-induced ulcerative colitis. MATERIALS AND METHODS: Ulcerative colitis was induced by single intrarectal injection of 120 mg/kg TNBS. Test groups were treated with simvastatin (10 mg/kg, p.o.) or rosuvastatin (10 mg/kg, p.o.). Colonic mucosal inflammation was evaluated clinically, biochemically, and histologically. RESULT: Disease activity index score in TNBS-treated rats, as determined by weight loss, stool consistency, fecal occult blood, were significantly lowers in simvastatin or rosuvastatin-treated rats than TNBS-treated animals. Simvastatin or rosuvastatin counteracted the reduction in colon length, decreased colon weight, neutrophil accumulation, and tumor necrosis factor-alpha level in TNBS-induced colitis. Simvastatin and rosuvastatin also inhibited the increase in oxidative stress levels after TNBS administration. CONCLUSIONS: These results suggest that simvastatin and rosuvastatin significantly ameliorate experimental colitis in rats, and these effects could be explained by their anti-inflammatory and antioxidant activity.

Amelioration of cisplatin-induced nephrotoxicity by statins.

OBJECTIVES: This study aimed to investigate the protective effect of simvastatin (SIM) and rosuvastatin (RST) on cisplatin (CIS)-induced nephrotoxicity. MATERIALS AND METHODS: Adult female Wistar rats were divided into six groups: control group (Group 1) received 0.5% sodium carboxy methyl cellulose, group 2 and group 3 received SIM and RST for 10 days, respectively, and group 4 was injected single dose of CIS (7 mg/kg, i.p.). Group 5 and 6 were treated with SIM (10 mg/kg, p.o.) and RST (10 mg/kg, p.o.) for 10 days, respectively. All groups received cisplatin on the 5(th) day of treatment. Renal function tests like serum creatinine, urea, BUN, albumin, calcium, uric acid and magnesium, serum lipids, and markers of oxidative stress such as renal malondialdehyde (MDA) level and superoxide dismutase (SOD) and catalase (CAT) activities were measured. All tissues were investigated for histopathological changes. RESULT: CIS reduced the renal function, which was reflected with significant increase in serum urea, BUN, serum creatinine, uric acid and also significant decrease serum calcium, magnesium, albumin levels. In addition, cisplatin caused renal tubular damage with a higher MDA level, depletion of SOD and CAT activity, and elevation of serum lipids. SIM or RST ameliorate CIS induced renal damage due to improvement in renal function, oxidative stress, suppression of serum lipids, and histological alteration. CONCLUSIONS: This finding suggests that simvastatin and rosuvastatin may have a protective effect against cisplatin-induced kidney damage via amelioration of lipid peroxidation as well as due to improvement of renal function, and lipid-lowering effects.