The objective of present work was to utilize potential of nanostructured lipid carriers (NLCs) for improvement in oral bioavailability of raloxifene hydrochloride (RLX). RLX loaded NLCs were prepared by solvent diffusion method using glyceryl monostearate and Capmul MCM C8 as solid lipid and liquid lipid, respectively. A full 3(2) factorial design was utilized to study the effect of two independent parameters namely solid lipid to liquid lipid ratio and concentration of stabilizer on the entrapment efficiency of prepared NLCs. The statistical evaluation confirmed pronounced improvement in entrapment efficiency when liquid lipid content in the formulation increased from 5% w/w to 15% w/w. Solid-state characterization studies (DSC and XRD) in optimized formulation NLC-8 revealed transformation of RLX from crystalline to amorphous form. Optimized formulation showed 32.50 ± 5.12 nm average particle size and -12.8 ± 3.2 mV zeta potential that impart good stability of NLCs dispersion. In vitro release study showed burst release for initial 8 h followed by sustained release up to 36 h. TEM study confirmed smooth surface discrete spherical nano sized particles. To draw final conclusion, in vivo pharmacokinetic study was carried out that showed 3.75-fold enhancements in bioavailability with optimized NLCs formulation than plain drug suspension. These results showed potential of NLCs for significant improvement in oral bioavailability of poorly soluble RLX.

The present study demonstrates the application of 3 2 full factorial design for optimization of berberine loaded liposome for oral administration. Thin film hydration method was used to prepare liposome and optimization was done by 3 2 full factorial designs combined with desirability function. Nine formulations were prepared by using different drug : lipid and soyphosphatidylcholine : cholesterol (SPC:CHOL) ratios and evaluated for entrapment efficiency and vesicle size. The statistical validity of model was done by analysis of variance (ANOVA). Response surface graph and contour plots were used to understand the effect of variables on responses. The optimized formulation with 0.782 desirability value was prepared and evaluated for responses. The results of entrapment efficiency and vesicle size were found to be very close with the predicted values. In addition, an optimized formulation was also characterized for zeta potential, in vitro drug release and morphology. The formulation was found to be spherical shape with an average diameter of 0.823 nm and -1.93 mV zeta potential and also shows sustained release pattern. These results support the fact that 3 2 full factorial designs with desirability function could be effectively used in optimization of berberine loaded liposome.

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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.

Currently, the entire globe is under the deadliest pandemic of Covid-19 caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). At present, no specific treatment is available to combat COVID-19 infection. Euphorbia hirta (Euphorbiaceae) have been reported for a variety of biological activities, including antiviral. The present investigation aimed to identify potential phytoconstituents of the plant E. hirta from the category flavonoids and coumarins against the SARS-CoV-2 using in silico approach. The molecular docking studies were performed using two different targets of SARS-CoV-2, namely Main protease (Mpro; PDB ID: 6M2N) and RNA-dependent RNA polymerase (RdRp; PDB ID: 7BW4). Based on the molecular docking study in comparison with standard drug, four compounds, namely Euphrobianin, Quercetin, 3-o-alpha-rhamnoside, Isoquercitrin, and rutin, were screened against the target Mpro. Three phytoconstituents, euphorbianin, myricetin, and rutin, were screened against the target RdRp. In the in silico toxicity studies of screened phytoconstituents, except myrectin all were predicted safe. Results of euphorbianin and rutin were found more interesting as both compounds had high binding affinity against both targets. Finally, we want to conclude that euphrobianin, quercetin 3-o-alpha-rhamnoside, isoquercitrin, and rutin could be further explored rapidly as they may have the potential to fight against COVID-19.