Melatonin delivered in solid lipid nanoparticles ameliorated its neuroprotective effects in cerebral ischemia.

The current study explores the potential of melatonin (MLT)-loaded solid lipid nanoparticles (MLT-SLNs) for better neuroprotective effects in ischemic stroke. MLT-SLNs were prepared using lipid matrix of palmityl alcohol with a mixture of surfactants (Tween 40, Span 40, Myrj 52) for stabilizing the lipid matrix. MLT-SLNs were tested for physical and chemical properties, thermal and polymorphic changes, in vitro drug release and in vivo neuroprotective studies in rats using permanent middle cerebral artery occlusion (p-MCAO) model. The optimized MLT-SLNs showed particle size of ∼159 nm, zeta potential of -29.6 mV and high entrapment efficiency ∼92%. Thermal and polymorphic studies showed conversion of crystalline MLT to amorphous form after its entrapment in lipid matrix. MLT-SLNs displayed a sustained release pattern compared to MLT dispersion. MLT-SLNs significantly enhanced the neuroprotective profile of MLT ascertained by reduced brain infarction, recovered behavioral responses, low expression of inflammatory markers and improved oxidation protection in rats. MLT-SLNs also showed reduced hepatotoxicity compared to p-MCAO. From these outcomes, it is evidenced that MLT-SLNs have improved neuroprotection as compared to MLT dispersion and thereby present a promising approach to deliver MLT to the brain for better therapeutic outcomes in ischemic stroke.

Enhanced Antidepressant Activity of Nanostructured Lipid Carriers Containing Levosulpiride in Behavioral Despair Tests in Mice.

The potential of levosulpiride-loaded nanostructured lipid carriers (LSP-NLCs) for enhanced antidepressant and anxiolytic effects was evaluated in the current study. A forced swim test (FST) and tail suspension test (TST) were carried out to determine the antidepressant effect whereas anxiolytic activity was investigated using light-dark box and open field tests. Behavioral changes were evaluated in lipopolysaccharide-induced depressed animals. The access of LSP to the brain to produce therapeutic effects was estimated qualitatively by using fluorescently labeled LSP-NLCs. The distribution of LSP-NLCs was analyzed using ex vivo imaging of major organs after oral and intraperitoneal administration. Acute toxicity studies were carried out to assess the safety of LSP-NLCs in vivo. An improved antidepressant effect of LSP-NLCs on LPS-induced depression showed an increase in swimming time (237 ± 51 s) and struggling time (226 ± 15 s) with a reduction in floating (123 ± 51 s) and immobility time (134 ± 15 s) in FST and TST. The anxiolytic activity in the light-dark box and open field tests exhibited superiority over LSP dispersion. Near-infrared images of fluorescently labeled LSP-NLCs demonstrated the presence of coumarin dye in the brain after 1 h of administration. An acute toxicity study revealed no significant changes in organ-to-body weight ratio, serum biochemistry or tissue histology of major organs. It can be concluded that nanostructured lipid carriers can efficiently deliver LSP to the brain for improved therapeutic efficacy.

Augmented Oral Bioavailability and Prokinetic Activity of Levosulpiride Delivered in Nanostructured Lipid Carriers.

The present study is aimed to develop and optimize levosulpiride-loaded nanostructured lipid carriers (LSP-NLCs) for improving oral bioavailability and prokinetic activity of LSP. LSP-NLCs were optimized with D-optimal mixture design using solid lipid, liquid lipid and surfactant concentrations as independent variables. The prepared LSP-NLCs were evaluated for physicochemical properties and solid-state characterization. The in vivo oral pharmacokinetics and prokinetic activity of LSP-NLCs were evaluated in rats. LSP-NLCs formulation was optimized at Precirol® ATO 5/Labrasol (80.55/19.45%, w/w) and Tween 80/Span 80 concentration of 5% (w/w) as a surfactant mixture. LSP-NLCs showed a spherical shape with a particle size of 152 nm, a polydispersity index of 0.230 and an entrapment efficiency of 88%. The DSC and PXRD analysis revealed conversion of crystalline LSP to amorphous state after loading into the lipid matrix. LSP-NLCs displayed a 3.42- and 4.38-flods increase in AUC and Cmax after oral administration compared to LSP dispersion. In addition, LSP-NLCs showed enhanced gastric emptying (61.4%), intestinal transit (63.0%), and fecal count (68.8) compared to LSP dispersion (39.7%, 38.0% and 51.0, respectively). Taken together, these results show improved oral bioavailability and prokinetic activity of LSP-NLCs and presents a promising strategy to improve therapeutic activity of LSP for efficient treatment of gastric diseases.

Cytotoxic Evaluation and Molecular Docking Studies of Aminopyridine Derivatives as Potential Anticancer Agents.

BACKGROUND: The development of resistance to available anticancer drugs is increasingly becoming a major challenge and new chemical entities could be unveiled to compensate for this therapeutic failure. OBJECTIVES: The current study demonstrated whether N-protected and deprotected amino acid derivatives of 2- aminopyridine could attenuate tumor development using colorectal cancer cell lines. METHODS: Biological assays were performed to investigate the anticancer potential of synthesized compounds. The in silico ADME profiling and docking studies were also performed by docking the designed compounds against the active binding site of beta-catenin (CTNNB1) to analyze the binding mode of these compounds. Four derivatives 4a, 4b, 4c, and 4d were selected for investigation of in vitro anticancer potential using colorectal cancer cell line HCT 116. The anti-tumor activities of synthesized compounds were further validated by evaluating the inhibitory effects of these compounds on the target protein beta-catenin through in vitro enzyme inhibitory assay. RESULTS: The docking analysis revealed favorable binding energies and interactions with the target proteins. The in vitro MTT assay on colorectal cancer cell line HCT 116 and HT29 revealed potential anti-tumor activities with an IC50 range of 3.7-8.1µM and 3.27-7.7 µM, respectively. The inhibitory properties of these compounds on the concentration of beta-catenin by ELISA revealed significant percent inhibition of target protein at 100 µg/ml. CONCLUSION: In conclusion, the synthesized compounds showed significant anti-tumor activities both in silico and in vitro, having potential for further investigating its role in colorectal cancer.

HPLC method development and validation for in vitro and in vivo quantification of vancomycin in rabbit plasma.

Vancomycin (VAN) is an effective antibiotic due to its broad-spectrum bactericidal action. High performance liquid chromatography (HPLC), a powerful analytical technique is used for the in vitro/ in vivo quantification of VAN. The current study was aimed to detect the VAN from in vitro as well as the plasma after the extraction from blood of rabbits. The method was developed and validated according to International Council on Harmonization (ICH) Q2 R1 guidelines. Results showed that the peak of VAN was recorded at 2.96 and 2.57 min, respectively in vitro and serum. The coefficient of VAN turned out to be >0.9994 each for in vitro and in vivo samples. VAN was found linear in the range of 6.2-25000ng/mL. The values of accuracy and precision in terms of coefficient of variation (CV) were less than 2%, indicating the validity of the method. The values for LOD and LOQ were estimated to be 1.5 and 4.5ng/mL, correspondingly, which were lower than the values calculated from in vitro media. Furthermore, the score of the greenness found out to be 0.81, depicting good score using AGREE tool. It was concluded that the developed method was found accurate, precise, robust, rugged, linear, detectable and quantifiable at prepared analytical concentrations and could be used for in vitro and in vivo VAN determination.

Correction to: Genome wide meta-analysis of cDNA datasets reveals new target gene signatures of colorectal cancer based on systems biology approach.

[This corrects the article DOI: 10.1186/s40709-020-00118-1.].

Development of fast dissolving tablets of flurbiprofen by sublimation method and its in vitro evaluation

Flurbiprofen belongs to Biopharmaceutical Classification System (BCS) class II drugs which are poorly soluble in water. The objective of present research work was to prepare fast dissolving tablets of Flurbiprofen using varying concentrations of three different sublimating agents to improve the dissolution rate. Seven formulations were prepared containing different concentrations of camphor, ammonium bicarbonate and thymol as sublimating agent along with primogel as a superdisintegrant. Tablets were manufactured by direct compression method. The prepared tablets were evaluated for pre-compression and post-compression parameters result, For all formulations result was within official limits. FTIR studies revealed that there were no interactions between the drug and the excipients used. From in vitro drug release studies it was concluded that the formulations F6 and F7 containing 10% and 15% of thymol showed fast drug release of 100.00% and 100.84% respectively in 30 minutes. Formulations containing camphor (F2 & F3) and ammonium bicarbonate (F4 & F5) as sublimating agents showed a drug release of less than 80%, while the control formulation F1 having no sublimating agent showed 49.14% of drug release in 30 minutes. Thus thymol can successfully be used to formulate fast dissolving tablets of flurbiprofen by sublimation method with much better dissolution profile

Calendula extract: effects on mechanical parameters of human skin.

The aim of this study was to evaluate the effects of newly formulated topical cream of Calendula officinalis extract on the mechanical parameters of the skin by using the cutometer. The Cutometer 580 MPA is a device that is designed to measure the mechanical properties of the skin in response to the application of negative pressure. This non-invasive method can be useful for objective and quantitative investigation of age related changes in skin, skin elasticity, skin fatigue, skin hydration, and evaluation of the effects of cosmetic and antiaging topical products. Two creams (base and formulation) were prepared for the study. Both the creams were applied to the cheeks of 21 healthy human volunteers for a period of eight weeks. Every individual was asked to come on week 1, 2, 3, 4, 5, 6, 7, and 8 and measurements were taken by using Cutometer MPA 580 every week. Different mechanical parameters of the skin measured by the cutometer were; R0, R1, R2, R5, R6, R7, and R8. These were then evaluated statistically to measure the effects produced by these creams. Using ANOVA, and t-test it was found that R0, and R6 were significant (p <0.05) whereas R1, R2, R5, R7, R8 were insignificant (p > 0.05). The instrumental measurements produced by formulation reflected significant improvements in hydration and firmness of skin.