ABSTRACT
The objective of this study was to enhance the corneal permeation of gatifloxacin (GTX) using cubosomal nanoparticle as a delivery system. Cubosomal nanoparticle loaded with GTX was prepared and subjected for in vitro and in vivo investigations. The prepared GTX-loaded cubosomal particles exhibited nanoparticle size of 197.46 ± 9.40 nm and entrapment efficiency of 52.8% ± 2.93. The results of ex vivo corneal permeation of GTX-loaded cubosomal dispersion show approximately 1.3-fold increase compared to GTX aqueous dispersion. The incorporation of GTX into cubosomal particles resulted in a fourfold reduction in the minimum inhibitory concentration (MIC) value for the GTX cubosomal particles relative to GTX aqueous dispersion. Furthermore, the enhanced corneal penetration of GTX-loaded cubosomal dispersion compared was evident by a significant decrease in the area % of corneal opacity in MRSA infected rats. Moreover, these results were confirmed by photomicrographs of histological structures of corneal tissues from rats treated with GTX-cubosomal dispersion which did not present any change compared to that of the normal rat corneas. In conclusion, treatment of ocular bacterial infections and reduction in the probability of development of new resistant strains of MRSA could be accomplished with GTX-loaded cubosomal nanoparticles.
ABSTRACT
Soil hosts myriads of living organisms with the extensive potential to produce bioactive compounds. Bacteria are the major soil inhabitants that represent a rich reservoir for antibiotic production along with their role in recycling nutrients and maintenance of the soil ecosystem. Here, from 55 tested soil samples, we isolated and identified a novel antibiotic-producing bacterial strain with a phylogenetically closest match to Bacillus subtilis sp. based on BLASTN search of GenBank for the 16S rRNA gene sequence. We characterized this novel strain through microscopic, biochemical, and molecular techniques, combined with testing its potential antimicrobial activity. Chemical studies revealed that the antibiotic produced by this strain is a glycopeptide. It exhibited profound activity against both methicillin-resistant Staphylococcus aureus (MRSA) and Candida albicans. The antibiotic is optimally produced at 37 °C after 28 h of growth. The biocompatibility of the extracted antibiotic was tested over a wide range of factors including temperature, pH, surfactants, and metal salts. To confirm its therapeutic potential, a sterile solution of the antibiotic was tested in vivo against bacteria-induced keratitis in rats where significant healing activity was recorded. Hence, this soil Bacillus strain may lead to the development of novel antibiotics for the treatment of human pathogens.
ABSTRACT
The objective of the present study was to enhance ocular antifungal activity of fluconazole (FCZ) in treatment of keratomycosis through incorporation into cubosomal nanoparticles. FCZ-loaded cubosomal dispersions were prepared by emulsification method according to 23 full factorial design. Design-Expert® software was used to study the effects of different formulation factors on properties of FCZ-loaded cubosomal dispersions and select the optimal formulation. Eight FCZ-loaded cubosomal dispersions were prepared and were in vitro and in vivo evaluated. In vitro, the results revealed that the optimum formula exhibited a mean particle size of 48.17 ± 0.65 nm and entrapped 85.70 ± 2.56% of FCZ. The ex vivo permeation study confirmed a two-fold enhancement in FCZ permeation through rabbit cornea compared to aqueous FCZ solution. Furthermore, in vivo ocular tolerance and histopathological studies proved the efficacy and safety FCZ-loaded cubosomal dispersion in treatment of induced keratomycosis in rats compared to aqueous FCZ solution after topical ocular application. In conclusion, the obtained results indicated that cubosomes could be promising ocular drug delivery system for enhancing antifungal activity of FCZ in treatment of fungal keratitis in rats. Graphical abstract.
