A study on enhanced intestinal permeability of clarithromycin nanoparticles

Abstract

The main objective of the present study was to determine the permeability of clarithromycin (CLA)-PLGA nanoparticles using single-pass intestinal perfusion technique in rats. Clarithromycin nanoparticles were prepared by nano-precipitation according to the modified quasi emulsion solvent diffusion technique and evaluated for their physicochemical characteristics. Permeability coefficients (P eff ) in anaesthetized rats were determined at 3 different concentrations. Drug solution or suspensions in PBS was perfused through a cannulated jejunal segment and samples were taken from outlet tubing at different time points up to 90 min. Microbiological assay of CLA and phenol red in the samples were analyzed using an agar well diffusion procedure and HPLC method respectively. The average particle size of prepared nanoparticles was 305 ± 134 nm. The mean P eff of CLA solution in concentrations of 150, 250 and 400 µg/mL was found to be 1.20 (±0.32) ×10 -3 , 9.62 (±0.46) ×10 -4 , and 1.36 (±0.95) ×10 -3 cm/sec, respectively. The corresponding values for the same concentration of nanoparticles were found to be 2.74 (±0.73) ×10 -3 , 2.45 (±0.88) ×10 -3 , and 3.68 (±0.46) ×10 -3 cm/s, respectively. The two-tailed Student's t-test showed that the intestinal permeability of CLA nanoparticle suspensions in prepared concentrations were significantly increased in comparison with its solution.Uniterms: Clarithromycin/nanoparticles/ permeability. Single-Pass Intestinal Perfusion. Intestinal permeability.O objetivo principal do presente estudo foi determinar a permeabilidade de nanopartículas de claritromicina (CLA)-PLGA, utilizando a técnica de perfusão intestinal de passo único em ratos. As nanopartículas de claritromicina foram preparadas por nanoprecipitação, de acordo com a técnica modificada de difusão de solvente quase-emulsão, e suas características físico-químicas avaliadas. Os coeficientes de permeabilidade (P eff ) em ratos anestesiados foram determinados em três concentrações diferentes. A solução, ou suspensões, do fármaco em PBS foi perfundida através do segmento de jejuno canulado e as amostras foram tomadas do tubo externo em diferentes tempos até 90 minutos. Os ensaios microbiológico de CLA e de vermelho de fenol das amostras foram realizados, utilizando-se o procedimento de difusão em poço de ágar e de CLAE, respectivamente. O tamanho médio das partículas das nanopartículas preparadas foi de 305 ± 134 nm. O P eff médio da solução de CLA em concentrações de 150, 250 and 400 µg/mL foi de 1.20(±0.32)×10 -3 , 9.62(±0. INTRODUCTIONOral administration remains the most convenient and useful route for delivering most pharmaceutical agents. However, the major problem of many orally administered drugs is to overcome several barriers before reaching their target site (Cook, Shenoy, 2003;Rao et al., 2008). Several approaches have been applied in order to improve the oral bioavailability of poorly permeable and soluble compounds intended for oral administration. Using nanoparticulate drug delivery system is considered as one of...

Intestinal Permeability of Artesunate-Loaded Solid Lipid Nanoparticles Using the Everted Gut Method

“…Improvement in the intestinal permeability has been largely attributed to the tiny size of SLN which increases contact surface area and prolongs drug residence time. This facilitates adhesion to the gut mucosal layer and penetration into the intervillous space leading to a higher diffusion rate of the drug [24, 26, 49]. In addition, reduction in particle size can cause augmented dissolution and saturation solubility which elevates the concentration gradient between the intestinal epithelial cells and the underlying mesenteric circulation resulting in improved drug absorption [26].…”

“…However, the overall absorption of orally administered drugs depends on a critical rate-limiting step, which is its permeability through the intestinal epithelium [24]. A wide research has thus been done on the permeability of nanoparticles over the past years which correlated with improved therapeutic activity [25, 26].…”

Evaluation of food effect on the oral absorption of clarithromycin from immediate release tablet using physiological modelling

“…The experimental values for clarithromycin solubility at the different pH and biorelevant media were incorporated in the model. The effective permeability of clarithromycin (P eff , 20 × 10 −4 cm/s) was estimated using GastroPlus™, based on the reported intestinal permeability of the drug in rat jejunum (1.20 × 10 −3 cm/s) (Zakeri‐Milani et al, ). The default values for precipitation time (900 s), particle density (1.2 g/ml) and particle size (25 μm) were used.…”

Study of Antimicrobial Effects of Clarithromycin Loaded PLGA Nanoparticles against Clinical Strains of Helicobacter pylori

“…We have prepared CLR-loaded PLGA nanoparticles with improved physicochemical properties [8]. CLR in the prepared nano formulation has also shown to have enhanced intestinal permeability in animal model [11]. In the current research the antimicrobial activity of the prepared CLR-loaded PLGA nanoparticles was evaluated against clinical strains of H. pylori isolated from gastric biopsies of patients with gastritis, duodenal ulcer, peptic ulcer, and gastroesophageal reflux disease undergoing endoscopy, in comparison with untreated drug.…”

“…The mean particle-size of nanoparticles were determined using a laser diffraction particle-size analyzer (Sald 2101, Shimadzu, Japan) equipped with Wing software (version 1.20) (Zakeri-Milani et al, 2014). Scanning electron microscopy (SEM) (LEO 440i, Leo Electron Microscopy Ltd., Cambridge, UK) at an accelerating voltage of 20 kV was used to examine the morphology of the nanoparticles [11]. Measurements were performed in distilled water adjusted to pH 8 and a conductivity of 50 S/cm.…”