OBJECTIVE: A sensitive method for the estimation of CRM in plasma, as well as fecal matter-based solid self-nano emulsifying drug delivery system (S-SNEDDS), has been reported for the first time.

METHODS: A bioanalytical method was optimized using Box-Behnken Design having 13 runs and 3 responses. The optimized method was developed using methanol and water (70:30 v/v) with a flow rate of 1 mL/min. Quercetin was used as an internal standard. A specificity test was also performed for the developed CRM solid self-nano emulsifying drug delivery system.

RESULTS: The retention time of CRM was found to be 14.18 minutes. The developed method was validated and found to be linear in the range of 50-250 ng/mL with an R2 of 0.999. Accuracy studies indicated that CRM had a percentage recovery of less than 105% and more than 95%, respectively. Precision studies were carried out for inter, intraday, and inter-analyst precision, and the %RSD was found to be less than 2%. The limit of detection (LOD) and limit of quantification (LOQ) were found to be 3.37 ng/mL and 10.23 ng/mL, respectively. Stability studies for shortterm, long term and freeze-thaw cycles showed a %RSD of less than 2%, indicating the stability of CRM in the plasma matrix. Moreover, the blank fecal microbiota extract slurry did not show any peak at the retention time of CRM in a CRM-loaded solid nanoemulsifying drug delivery system containing fecal microbiota extract indicating its specificity.

MATERIAL AND METHOD: Two hundred discs of PEEK were prepared of 6 mm × 2 mm × 10 mm dimension. The discs were randomly divided into five groups (n = 40) for treatment, Group I: treatment with deionized distilled water (control group); Group II: PD therapy using curcumin PS; Group III: discs treated and abraded with air-borne particles (ABP) silica (30 μm particle size) modified alumina (Al); Group IV: ABP of alumina (110 μm particle size); and Group V: The PEEK were finished with 600-μm grit size straight diamond cutting bur installed in high speed hand-piece. The surface profilometer was used to evaluate the values of surface roughness (SRa) of pretreated PEEK discs. The discs were luted and bonded to discs of composite resin. The bonded PEEK samples were placed in Universal testing machine to evaluate shear BS. The type of BS failure for PEEK discs pre-treated with five regimes respectively was evaluated under stereo-microscope. The data was statistically analyzed using one-way ANOVA and the comparisons between mean values of shear BS were evaluated by Tukey's test (ρ≤0.05).

RESULTS: The PEEK samples pre-treated with diamond cutting straight fissure burs displayed statistically significant highest value of SRa values (3.258± 0.785 µm). Similarly, the shear BS was observed to be higher for the PEEK discs pre-treated with straight fissure bur (22.37±0.78 MPa). A comparable difference but not statistically significant difference was observed between PEEK discs pre-treated by curcumin PS and ABP-silica modified alumina (ρ ≥ 0.05).

MATERIALS AND METHODS: Curcumin and its analogues were subjected to docking using PDE4A, PDE4B, PDE4C and PDE4D as the targets. A data set comprising 18 analogues of curcumin, was used as ligands for docking of PDE4 subtypes. Curcumin was used as the standard for comparison. Docking was performed using AutoDock Vina 1.1.2 software integrated in LigandScout 4.1. During this process water molecules were removed from proteins, charges were added and receptor structures were minimised by applying suitable force fields. The docking scores were compared, and the selectivity of compounds for PDE4B over PDE4D was calculated as well.

RESULTS: All curcumin analogues used in the study showed good binding affinity with all PDE4 subtypes, with evident selectivity towards PDE4B subtype. Analogue A11 provides the highest binding affinity among all ligands.

OBJECTIVE: In the present study, BBP was investigated for it's in vivo innate and adaptive immune responses mediated by different humoral and cellular immune factors.

METHODS: Male Balb/c mice were orally fed with BBP (5, 10 and 20 mg/kg) for a period of 14 days and immunized with sheep red blood cells (sRBC) on day 0 for the determination of adaptive responses. The effects of BBP on phagocytosis process of neutrophils isolated from blood of treated/untreated animals were determined. The ceruloplasmin and lysozyme serum levels and myeloperoxidase (MPO) plasma level were also monitored. The mechanism was further explored by assessing its effects on the proliferation of T and B lymphocytes, T-lymphocytes subsets CD4+ and CD8+ and on the secretion of Th1/Th2 cytokines as well as serum immunoglobulins (IgG, IgM) and delayed type hypersensitivity (DTH) reaction.

RESULTS: BBP showed a significant dose-dependent reduction on the migration of neutrophils, Mac-1 expression, phagocytic activity and reactive oxygen species (ROS) production. In comparison to the sensitized control group, a dose-dependent inhibition was observed on lymphocyte proliferation along with the downregulation of effector cells expression and release of cytokines. Moreover, a statistically significant decrease was perceived in serum levels of ceruloplasmin, lysozyme and immunoglobulins and MPO plasma level of BBP-treated mice. BBP also dose-dependently inhibited sheep red blood cells (sRBC)-induced swelling rate of mice paw in DTH.