Solid lipid nanoparticles of irbesartan: preparation, characterization, optimization and pharmacokinetic studies

ABSTRACT Irbesartan is an antihypertensive with limited bioavailability and solid lipid nanoparticles (SLN) is one of the approaches to improve bioavailability. Solid lipid nanoparticles were prepared using glyceryl monostearate by solvent emulsification method followed by probe sonication. Irbesartan loaded SLNs were characterized and optimized by parameters like particle size, zeta potential, surface morphology entrapment efficiency and in vitro release. The optimized formulation was then further evaluated for the pharmacokinetic studies in Wistar rats. Irbesartan-loaded SLN of particle size 523.7 nm and 73.8% entrapment efficiency showed good bioavailability in Wistar rats and also showed optimum stability in the studies. The SLN prepared using glyceryl monostearate by solvent emulsification method leads to improve bioavailability of the drug.

Estudo e determinação teórica de propriedades físico-químicas de fármacos anti-hipertensivos inibidores da Enzima Conversora de Angiotensina / Theoretical study and determination of physicochemical properties of antihypertensive angiotensin-converting enzyme inhibitors

O pacote de softwares SpartanTM vs 04 foi utilizado para calcular algumas propriedades físico-químicas de uma série de inibidores da Enzima Conversora de Angiotensinogênio ECA. Simultaneamente, o pacote MarvinSketch 5.0.0 foi empregado para calcular o Coeficiente de Partição P dos inibidores. Através da análise dos resultados, conclui-se que: a) o arranjo termodinâmico mais estável desses inibidores mimetiza aquele dos resíduos pré-terminais da angiotensina II, b) há grande similaridade entre as cargas dos átomos que se ligam à macromolécula e c) os cálculos mostram diferenças significativas entre os valores de P para os inibidores. Portanto, as diferenças farmacológicas existentes entre os inibidores estão mais intimamente relacionadas ao coeficiente de partição do que à capacidade destes de inibir o sítio ativo da ECA.

The software package SpartanTM 4.0 was employed to calculate some physicochemical properties of a series of available ACE inhibitors. Simultaneously, the program MarvinSketch 5.0.0 was employed to calculate the partition coefficients (P) of the same compounds. After analyzing the results, we conclude that: a) from a thermodynamic point of view, the most stable conformer of each inhibitor resembles, as expected, the most stable spatial arrangement of the preterminal residues of angiotensin II; b) there is great similarity among the charge profiles of the potential binding sites of all the inhibitors; c) there are large differences in P among these compounds. Summing up, the pharmacological differences reported between the inhibitors are more closely linked to their lipophilic properties than to their capacity to block the ACE active center.

Reportes y entrevistas del American College of Cardiology: New Orleans 2007 / Report and interviews of the American College of Cardiology: New Orleans 2007

Este documento es publicación de la Canadian Medical Association y revisado por el Dr. Andreas Wieldosz del Hospita de Ottawa. Su contenido tiene propósitos educativos e informativos, sobre las investigaciones más recientes, Está dirigido primordialmente a médicos en atención primaria y se le sugiere al lector consultar las respectivas publicaciones originales e información relacinada, antes de tomar las acciones mencionadas en este reporte.

The hyperglycemia induced by angiotensin II in rats is mediated by AT1 receptors

We have shown that the renin-angiotensin system (RAS) is involved in glucose homeostasis during acute hemorrhage. Since almost all of the physiological actions described for angiotensin II were mediated by AT1 receptors, the present experiments were designed to determine the participation of AT1 receptors in the hyperglycemic action of angiotensin II in freely moving rats. The animals were divided into two experimental groups: 1) animals submitted to intravenous administration of angiotensin II (0.96 nmol/100 g body weight) which caused a rapid increase in plasma glucose reaching the highest values at 5 min after the injection (33 per cent of the initial values, P<0.01), and 2) animals submitted to intravenous administration of DuP-753 (losartan), a non-peptide antagonist of angiotensin II with AT1-receptor type specificity (1.63 µmol/100 g body weight as a bolus, iv, plus a 30-min infusion of 0.018 µmol 100 g body weight-1 min-1 before the injection of angiotensin II), which completely blocked the hyperglycemic response to angiotensin II (P<0.01). This inhibitory effect on glycemia was already demonstrable 5 min (8.9 ñ 0.28 mM, angiotensin II, N = 9 vs 6.4 ñ 0.22 mM, losartan plus angiotensin II, N = 11) after angiotensin II injection and persisted throughout the 30-min experiment. Controls were treated with the same volume of saline solution (0.15 M NaCl). These data demonstrate that the angiotensin II receptors involved in the direct and indirect hyperglycemic actions of angiotensin II are mainly of the AT1-type.

Serum angiotensin converting enzyme activity in children with diabetes mellitus

Scrum levels of angiotensin converting enzyme were measured in 21 children with type I diabetes mellitus and 13 healthy children. Diabetic subjects were excluded if they had hypertension; liver diseases; or kidney diseases. None of the children were receiving any medications except insulin in diabetic group. After an overnight fasting, blood sample was taken from each child for determination of fasting blood suger; glycosylated haemoglobin; and angiotensin converting enzyme. Data were analysed according to the non-paired student's t-test and linear regression analysis. Levels of angiotensin converting enzyme were significantly elevated in diabetic group as compared with control subjects [33.76 + 6.6 U/l vs 26.3 + 4.76 U/l .t = 3.82 and p<0.001]. No correlation was found between angiotensin converting enzyme levels and glycosylated haemoglobin or fasting blood glucose values. Many factors could contribute to elevation of this enzyme in diabetic children; increased release from damaged vasculature; subclinical hepatic impairment and insulin defeciency and/ or resistance