Mucoadhesive buccal tablets with propranolol hydrochloride: Formulation development and in vivo performances in experimental essential hypertension.

The objective of this study was to formulate extended-release mucoadhesive buccal tablets of propranolol hydrochloride in order to provide a prolonged absorption of propranolol hydrochloride from the buccal mucosa and to reduce presystemic metabolism and thus provide a better therapeutic effect. Besides, the aim was to perform comparative in vivo pharmacokinetic and hemodynamic studies of the developed extended-release (ER) propranolol hydrochloride 10 mg mucoadhesive buccal tablets and commercial immediate-release (IR) propranolol hydrochloride 10 mg tablets in spontaneously hypertensive rats. Formulation with 15% polyethylene oxide showed the highest degree of propranolol hydrochloride permeation, satisfactory mucoadhesiveness, and extended-release of propranolol hydrochloride, thus it was selected for further in vivo study. The pharmacokinetic study in rats showed the superiority of ER mucoadhesive buccal tablets over IR tablets in terms of propranolol hydrochloride absorption extent (AUC values: 70.32 ± 19.56 versus 31.69 ± 6.97 µg·h/mL), although lower maximum plasma propranolol hydrochloride concentration (Cmax) was achieved. However, no statistically significant difference was observed in Cmax between these treatments. The hemodynamic study showed that ER mucoadhesive buccal tablets provide a more pronounced decrease primarily in heart rate, but also in systolic and diastolic arterial pressure, as well as a longer heart rate reduction compared to IR tablets.

Antibacterial graphene-based hydroxyapatite/chitosan coating with gentamicin for potential applications in bone tissue engineering.

Electrophoretic deposition process (EPD) was successfully used for obtaining graphene (Gr)-reinforced composite coating based on hydroxyapatite (HAP), chitosan (CS), and antibiotic gentamicin (Gent), from aqueous suspension. The deposition process was performed as a single step process at a constant voltage (5 V, deposition time 12 min) on pure titanium foils. The influence of graphene was examined through detailed physicochemical and biological characterization. Fourier transform infrared spectroscopy, field emission scanning electron microscopy, thermogravimetric analysis, X-ray diffraction, Raman, and X-ray photoelectron analyses confirmed the formation of composite HAP/CS/Gr and HAP/CS/Gr/Gent coatings on Ti. Obtained coatings had porous, uniform, fracture-free surfaces, suggesting strong interfacial interaction between HAP, CS, and Gr. Large specific area of graphene enabled strong bonding with chitosan, acting as nanofiller throughout the polymer matrix. Gentamicin addition strongly improved the antibacterial activity of HAP/CS/Gr/Gent coating that was confirmed by antibacterial activity kinetics in suspension and agar diffusion testing, while results indicated more pronounced antibacterial effect against Staphylococcus aureus (bactericidal, viable cells number reduction >3 logarithmic units) compared to Escherichia coli (bacteriostatic, <3 logarithmic units). MTT assay indicated low cytotoxicity (75% cell viability) against MRC-5 and L929 (70% cell viability) tested cell lines, indicating good biocompatibility of HAP/CS/Gr/Gent coating. Therefore, electrodeposited HAP/CS/Gr/Gent coating on Ti can be considered as a prospective material for bone tissue engineering as a hard tissue implant.

The role of artichoke leaf tincture (Cynara scolymus) in the suppression of DNA damage and atherosclerosis in rats fed an atherogenic diet.

CONTEXT: Polyphenols and flavonoids in artichoke leaf tincture (ALT) protect cells against oxidative damage. OBJECTIVES: We examined ALT effects on deoxyribonucleic acid (DNA) damage and lipid profiles in rat plasma and gene expression in rat aorta [haemeoxygenase-1 (HO1), haemeoxygenase-2 (HO2), NADPH oxidase 4 (NOX-4), monocyte chemoattractant protein-1 (MCP-1) and nuclear factor (erythroid-derived 2)-like 2 (Nrf2)]. MATERIALS AND METHODS: Eighteen male Wistar albino rats were divided into three groups (n = 6/group): The control group (CG) was fed with standard pellet chow for 11 weeks; the AD group was fed for a similar period of time with pellet chow supplemented with 2% cholesterol, 3% sunflower oil and 1% sodium cholate. The ADA group was fed with pellet chow (for 1 week), the atherogenic diet (see above) for the following 4 weeks and then with ALT (0.1 mL/kg body weight) and atherogenic diet for 6 weeks. According to HPLC analysis, the isolated main compounds in ALT were chlorogenic acid, caffeic acid, isoquercitrin and rutin. RESULTS: Normalized HO-1 [0.11 (0.04-0.24)] and MCP-1 [0.29 (0.21-0.47)] mRNA levels and DNA scores [12.50 (4.50-36.50)] were significantly lower in the ADA group than in the AD group [0.84 (0.35-2.51)], p = 0.021 for HO-1 [0.85 (0.61-3.45)], p = 0.047 for MCP-1 and [176.5 (66.50-221.25)], p = 0.020 for DNA scores. HO-1 mRNA was lower in the ADA group than in the CG group [0.30 (0.21-0.71), p = 0.049]. CONCLUSIONS: Supplementation with ALT limited the effects of the atherogenic diet through reduced MCP-1 expression, thereby preventing oxidative damage.

Gentamicin-Loaded Bioactive Hydroxyapatite/Chitosan Composite Coating Electrodeposited on Titanium.

Composite coating of antibiotic gentamicin (Gent), natural polymer chitosan (CS), and hydroxyapatite (HAP) was successfully assessed by applying the electrophoretic deposition (EPD) technique. EPD was performed under optimized deposition conditions (5 V, 12 min) on pure titanium plates, to obtain HAP/CS and HAP/CS/Gent composite coatings in a single step from three-component aqueous suspension, with favorable antibacterial properties. Composite coatings were characterized by X-ray diffraction (XRD), field emission scanning electron microscopy, Fourier transform infrared spectroscopy, thermogravimetric analysis, and X-ray photoelectron analysis, confirming the formation of composite HAP/CS and HAP/CS/Gent coatings on the titanium surface, which is due to intermolecular hydrogen bonds. Employing the XRD technique, HAP was detected by obtaining the characteristic diffraction maximums. Good antibacterial activity of the composite coating loaded with antibiotic (HAP/CS/Gent) was confirmed against Staphylococcus aureus and Escherichia coli, pointing to the high potential for bioapplication. Introduction of gentamicin in HAP/CS/Gent coating caused very mild cytotoxicity in the tested cell lines MRC-5 and L929. MTT testing was used to evaluate cell viability, and HAP/CS was classified as noncytotoxic.

Effects of atorvastatin and artichoke leaf tincture on oxidative stress in hypercholesterolemic rats.

UNLABELLED: BACKGROUNG/AIM: Since combining conventional drugs with herbal medicinal products is in current research focus and possible of great interest as therapy improvement way, the aim of this study was to determine the effects of well-established antiatherosclerotic drug atorvastatin (CAS number 134523-00-5) and commercially available artichoke leaf tincture (ALTINC), used as combined therapy, as well as to compare effects of these two treatments separately. METHODS: Experimental animals were divided into five groups: the group I (the control group of rats fed with standard diet during 11 weeks), and the remaining 4 groups of rats (II, III, IV and V) fed with standard diet during the first week and then with hypercholesterolemic diet during the next 10 weeks. The group II of rats were left without treatment, while in the groups III, IV and V were rats treated per os with atorvastatin (1.15 mg/kg body weight--b.w.), ALTINC (0.1 mL/kg b.w.) and their combination in same doses, respectively, for the last six weeks. RESULTS: The cholesterol rich diet led to pronounced hyperlipidemia which could not be overcame with the therapy. However, the therapy showed positive effects on abdominal aorta wall thickness and parameters of oxidative stress (malondialdehyde--MDA, proxidative-antioxidative balance--PAB) and antioxidative protection (reduced glutathione--GSH, paraoxanase 1--PON1, superoxide dismutase--SODA SH groups), especially ALTINC was successful in oxidative status improvement. CONCLUSION: Separate treatments comparison showed that artichoke leaf tincture is very potent antioxidant with beneficial effects in early stages of atherosclerosis. Since atorvastatin and constituents of ALTINC probably have different mechanisms of action, simultaneous use of both therapies could be beneficial but should be further investigated since our results showed that ALTINC is less effective when used in combination with atorvastatin.

An improved HPLC method with the aid of a chemometric protocol: simultaneous determination of atorvastatin and its metabolites in plasma.

The aim of the present study was to optimize a chromatographic method for the analysis of atorvastatin (acid and lactone forms), ortho- and para-hydroxyatorvastatin by using an experimental design approach. Optimization experiments were conducted through a process of screening and optimization. The purpose of a screening design is to identify the factors that have significant effects on the selected chromatographic responses, and for this purpose a full 23 factorial design was used. The location of the true optimum was established by applying Derringer's desirability function, which provides simultaneously optimization of all seven responses. The ranges of the independent variables used for the optimization were content of acetonitrile in mobile phase (60-70%), temperature of column (30-40 °C) and flow rate (0.8-1.2 mL min⁻¹). The influences of these independent variables were evaluated for the output responses: retention time of first peak (p-hydroxyatorvastatin) and of last peak (atorvastatin, lactone form), symmetries of all four peaks and relative retention time of p-hydroxyatorvastatin. The primary goal of this investigation was establishing a new simple and sensitive method that could be used in analysis of biological samples. The method was validated and successfully applied for determination of atorvastatin (acid and lactone forms) and its metabolites in plasma.