Predicting the intestinal permeability and oral absorbable fraction of Vancomycin–loaded Eudragit RS-100 nanoparticles using single-pass intestinal perfusion in rats

Abstract

Abstract One of the important factors which influence the efficacy of antibiotics is the size of the particle that affects the permeability and penetration of antimicrobial agents in infected tissue. Vancomycin hydrochloride (VCM), as a large hydrophilic antibiotic, is unable to pass through the intestinal barrier, this antibiotic is administered intravenously to treat systemic infections. One of the approaches to increasing the absorption and permeability of drugs is reducing the size of drugs. For this reason, in this study, the intestinal permeability coefficient and the oral absorbable fraction of Vancomycin nanoparticle were assessed compared to its routine form. To analyze Permeability effectiveness (Peff), absorbable fraction, and absorption number of Vancomycin in nanoparticle and solution form at a concentration of 200, 300, and 400 µg/ml and flow rate of 0.2 ml/min for 80 min, Single-pass intestinal perfusion(SPIP) method was performed. Data showed that the Effective permeability(Peff) of Vancomycin nanoparticles were 2.16, 1.43, and 2.66-fold higher than the routine form of Vancomycin at concentrations of 200, 300, and 400 µg/ml, respectively. Also, this result found a strong relationship between rat and human intestinal permeability. This means that the SPIP method could effectively predict the human Peff by rat model. Stability analysis of Vancomycin nanoparticles in 0, 1, and 2 hours illustrated no mark of corruption of the drug in nanoparticle form. Results showed that vancomycin nanoparticles had a better absorbable fraction and absorption number value than Vancomycin solution after oral drug administration.