Preparation and evaluation of a thermosensitive liposomal hydrogel for sustained delivery of danofloxacin using mesoporous silica nanoparticles

BACKGROUND: Sustained release delivery system can reduce the dosage frequency and maintain the therapeutic level of drugs for a longer time. Biodegradable, biocompatible and thermosensitive chitosan-beta-glycerophosphate (C-GP) solutions can solidify at body temperature and maintain their physical integrity for a longer duration. OBJECTIVES: To develop a novel delivery system based on the integration of liposomes in hydrogel using mesoporous silica nanoparticles (MSNs) for sustained release of danofloxacin in farm animals. METHODS: The MSNs were prepared using N-cetyltrimethylammonium bromide and tetraethylortho silica. The liposomes were prepared by thin film hydration method. C-GP solution containing danofloxacin-loaded MSN liposomes underwent different in-vitro tests, including evaluation of the entrapment efficiency, gelation time, morphology, drug release pattern as well as antimicrobial activities against S. aureus and E. coli. RESULTS: The mean pore size of MSNs was 2.8 nm and the mean MSN entrapment efficiency was 45%. Kinetics of danofloxacin release from liposomal hydrogel followed the Higuchi’s model. This formulation was capable of sustaining the danofloxacin release for more than 96 h. The FTIR studies showed that there were no interactions between danofloxacin and hydrogel excipients. Scanning electron microscopy (SEM) showed that the formed gel had a continuous texture, while the swelled gel in the phosphate buffer had a porous structure. Microbiological tests revealed a high antibacterial activity for lipomosal hydrogel of danofloxacin-loaded MSN comparable with danofloxacin solution. CONCLUSIONS: The liposomal hydrogel solidified at body temperature, effectively sustained the release of danofloxacin and showed in vitro antibacterial effects

Preparation and in vitro evaluation of chitosan-based films for the sustained delivery of enrofloxacin

The implantable drug products are developed mainly to sustain the drug release. This study was conducted to formulate and evaluate cross-linked films of chitosan/β-glycerophosphate (β-GP) for the sustained delivery of enrofloxacin (ENR). Two types of formulations, single-layer (F1 and F2) and triple-layer (F3 and F4) films, were prepared. In vitro drug release, kinetic modelling, Fourier transform infrared spectroscopy (FTIR) spectra, morphological and microbiological studies were performed. Drug release from F1 and F2 continued up to 5 hours but from F3 and F4, it was extended over 96 and 168 hours, respectively. The cumulative drug release for F1, F2, F3 and F4 were 72.6, 70.1, 90.5 and 82.4%, respectively. The inhibition zones of bacterial growth by using positive controls and single layer films were significantly greater than those of triple-layer films (p < 0.05), indicating sustained drug release pattern of the multi-layer films.These findings suggest that the triple-layer chitosan/ β-GP films could be effective to deliver ENR for a long period

Effect of 3,4-Methylenedioxymethamphetamine on Liver CYP2C19 Enzyme Activity in Isolated Perfused Rat Liver Using Omeprazole Probe

Background and purpose: This study aimed at investigating the effects of 3,4-Methyl​enedioxy​methamphetamine (MDMA) on liver cytochrome 2C19 enzyme activity, which is a major liver enzyme in the metabolism of a wide range of drugs, using omeprazole as a probe of the CYP2C19 activity in isolated perfused rat liver. Materials and methods: This experimental study was done in 20 male Sprague–Dawley (SD) rats (weighing 250–300 g). After isolating the animal liver, omeprazole was administered at 400 μm and the concentration of omeprazole and its metabolite were determined. The liver was then washed with perfusion buffer, and MDMA was transferred at 300 ng/ml unilaterally from the same liver for 30 minutes. After re-washing the liver with perfusion buffer, omeprazole was passed through the liver for second time and the metabolic ratio was determined after exposure to MDMA. This process was also done in a group of animals at 600 ng/ml of MDMA. Results: Analysis of data from three end-time intervals after exposure to liver at 300 and 600 ng/ml of MDMA, showed 26.6% and 20.6% reduction in the activity of CYP2C19. Findings showed that MDMA administration could significantly reduce the activity of CYP2C19. Conclusion: According to this study, liver exposure to MDMA can significantly reduce cytochrome 2C19 activity, but, further studies are needed to examine this issue more closely