Ariadna Lafourcade Prada

Development, stability and in vitro delivery profile of new loratadine-loaded nanoparticles

Purpose: Loratadine is used as antihistaminic without side effects in nervous systems. This drug is a weak base and it is absorbed from the intestine. The nitrogen of the pyridine ring is protonated in the stomach affecting the oral bioavailability. The aim of this paper was obtaining, characterize and evaluate the release profiles and the stability of a gastroresistant loratadine nanosuspension. Methods: The nanosuspension was prepared by the solvent displacement evaporation method, using three different polymers (Eudragit® L 100 55, Kollicoat® MAE 100P and PEG 4000) and Polysorbate 80. Dynamic Light Scattering was used for evaluating the particle size (PS), zeta potential, and conductivity of the nanosuspension. Loratadine release profiles were evaluated in simulated gastrointestinal fluids. The shelf and accelerated stability were assessed during three months. Results: Nanosuspension particle size was 45.94 ± 0.50 nm, with a low polydispersion index (PdI, 0.300). Kollicoat® MAE 100P produced a hard and flexible coating layer. In simulated intestinal fluids, the 100 percent of loratadine was released in 40 min, while in simulated stomach fluids the release was lesser than 5%. Nanosuspension presented a good physicochemical stability showing a reduction in PS and PdI after three months (43.29 ± 0.16 and 0.250; respectively). Conclusions: A promissory loratadine nanosuspension for loratadine intestinal delivery was obtained, by using a low energy method, which is an advantage for a possible scale up for practical purpose.

Antioxidant and Hepatoprotective Activity of a New Tablets Formulation from Tamarindus indica L.

Hepatotoxic chemicals damage liver cells primarily by producing reactive oxygen species. The decoction of the leaves of Tamarindus indica L. is used for liver disorders. In this work we evaluated the hepatoprotective activity of a tablet formulation of this plant. Thirty-five Sprague Dawley rats were randomly divided into five groups (n = 7). First group (I) is control group, fed with standard diet. Groups II to V (hepatotoxic groups) were subjected to a subcutaneous injection of CCl4 (0.5u2009mL/kg). Group II was negative control, fed with standard diet; group III was subjected to administration of Silymarin 150u2009mg/kg and groups IV and V were treated with tablets in dose of 100u2009mg/kg and 200u2009mg/kg, respectively. Lipid peroxidation and the activity of superoxide dismutase, catalase, and reduced glutathione were evaluated. Serum levels of alanine aminotransferase, aspartate aminotransferase, gamma-glutamine transferase, alkaline phosphatase, and a lipid profile were evaluated too. The tablets inhibit lipid peroxidation. The redox balance (SOD-CAT-GSH) remains normal in the experimental groups treated with tablets. The liver function using dose of 200u2009mg/kg of tablets was better than the other experimental groups. These results justify, scientifically, the ethnobotanical use of the leaves of Tamarindus indica L.

Development and Characterization of Cassia grandis and Bixa orellana Nanoformulations.

Cassia grandis and Bixa orellana are important plant species with folk use and great potential for phytopharmaceuticals. Nanodispersions are disperse systems of insoluble or immiscible substances in a liquid medium that may be prepared with or without coating polymers. To our knowledge, no studies were carried in order to achieve coating-polymer free nanoformulations using B. orellana extract or any C. grandis-based nanoformulations. Thus, on the present study we aimed to develop C. grandis nanoformulations using three different coating polymers (Eudragit® L 100 55, PEG 4000 and Kollicoat®), while B. orellana nanodispersions were obtained using different surfactants (polysorbate 80, polysorbate 20, polyethylene glycol 400 monooleate, polyethylene glycol 600 monooleate, polyethylene glycol 400 dioleate and polyethylene glycol 600 dioleate) as coating polymer-free nanoformulations. Characterization of nanoformulations was performed by different parameters, including particle size, polydispersity index and zeta-potential. Our results suggested that some optimal nanoformulations were obtained for both plant species. Moreover, possible stable behavior was observed during storage period for C. grandis (30 days) and B. orellana (21 days). On this context, the present study contributes to nanobiotechnology development of phytopharmaceuticals, allowing achievement of novel nano-delivery systems with two important folk medicinal plant extracts and making them potential products for innovative phytopharmaceuticals.

Cassia grandis Lf nanodispersion is a hypoglycemic product with a potent α-glucosidase and pancreatic lipase inhibitor effect

Purpose This study aimed to evaluate the hypoglycemic effect, antioxidant, α-glucosidase and lipase inhibitory activity, and the cytotoxicity of the Cassia grandis nanodispersion (CgND). Methods The hypoglycemic effect was evaluated in alloxan-induced diabetic mice. The particle size, polydispersion index, ζ-potential, and conductivity, as well as the drug-loaded content, were monitored in shelf-live, along a year. The delivery profile was evaluated in simulated intestinal fluids at pH 6.5 and 7.4. The antioxidant effect was evaluated as DPPH and ABTS inhibition. The murine α-glucosidase inhibitory activity and the lipase-inhibitory effect were evaluated in vitro. Cytotoxicity was evaluated by the Alamar blue test. Results CgND remained stable for a year in shelf conditions. The hypoglycemic effect in a dose of 10u202fmg/kg was not statistically different from glibenclamide 25u202fmg/kg. Nanoparticles released 100% of extract in 120u202fmin at pH 6.5 and 7.4. Nanodispersion exhibited a potent α-glucosidase and lipase-inhibitory effect with IC50 of 3.96 and 0.58u202fµg/mL, respectively. A strong antioxidant activity against DPPH (IC50 0.65u202fµg/mL) and ABTS (0.48u202fµg/mL) was also observed. The hypoglycemic effect could occur, at least in part, via antioxidant and α-glucosidase inhibition. CgND is non-cytotoxic in MRC-5 line cell. This nanodispersion is a promising nanotechnological product that could be used in pharmaceuticals for the treatment of Type II diabetes and related complications as obesity.

Cassia grandis fruit extract reduces the blood glucose level in alloxan-induced diabetic rats

INTRODUCTIONnCassia grandis Lf fruits are ethnobotanically used for digestive disorders, anemia, and for reducing blood glucose. However, there are no studies about the antidiabetic activity nor the oral toxicity of the plant fruit-extracts. This paper aims to evaluate the hypoglycemic effect of C. grandis fruits extract in vivo, and assess the acute oral toxicity, and sub-acute oral toxicity. The antioxidant activity and the α-glycosidase inhibitor effect were also evaluated.nnnMETHODSnThe extract was obtained by maceration of the fruit pulp with 70% hydroalcoholic solution (1:2, m:v). The extractive solution was concentrated in a vacuum rotary evaporator, up to a drug: solvent ratio of 2:1 (g/ml). Soluble solids, relative density, refractive index, pH, total phenolics, and flavonoids were determined. A preliminary phytochemical screening was made, followed by the quantitation of volatiles by GC/MS. The acute and sub-acute oral toxicity was evaluated in Sprague Dawley rats, by using biochemical and hematological parameters. The radical scavenging activity (DPPH, ABTS) and α-glycosidase inhibitory effect were tested. The hypoglycemic effect was assessed in alloxan-induced diabetic rats.nnnRESULTSnThe extract of C. grandis contains alkaloids, coumarins, flavonoids, free amino acids, amines, phenols, tannins, reduced sugars, resins, saponins, steroids, and triterpenes, plus 38 volatile compounds, being linalool the most abundant (1,66%). The extract exhibited an LD50u202f>u202f2000u202fmg/kg, and after a continuous administration (1000u202fmg/kg, 28-days), the hematological and biochemical parameters were normal. The extract showed hypoglycemic effect, being the dose 200u202fmg/kg no statistically different from glibenclamide at 25u202fmg/kg. Good antioxidant activity and a potent α-glycosidase inhibitory effect were also observed.nnnCONCLUSIONnC. grandis extract is an excellent hypoglycemic and non-toxic plant product. The hypoglycemic mechanism could be associated with the antioxidant effect and with the α-glycosidase inhibition. Up to the best of our knowledge, this is the first report on the hypoglycemic effect in vivo of C. grandis fruits extract.