Skin infectious diseases represent a global issue costing millions of dollars per year in developed countries. Antibiotic therapy is generally considered the gold standard to treat overt infections. However, the limited efficacy of transdermal drug delivery has currently directed the researcher attention towards new approaches to improve the topical release of active principles. In this context, an interdisciplinary study was aimed to develop innovative eudermic formulations based on the use of porous biocompatible particles, inside of which amikacin sulfate (AMK) was incorporated to obtain a saturated antimicrobial drug formulation, as drug reservoir. The active ingredient is released from the pores of the particles with a mechanism similar to the drug dissolution in solution. We determined the antimicrobial efficacy and the prolonged release time of the new drug formulation (silica particles coupled to 5% AMK) in comparison with the commercial product Dramigel® 5% AMK (Morgan s.r.l,VI). The antimicrobial activity of AMK, and Dramigel® was evaluated by MIC and MBC towards Gram-negative bacteria involved in skin infections (Escherichia coli, Klebsiella pneumoniae, and Enterobacter cloacae). In vitro AMK release from the formulation and Dramigel® was determined in Franz diffusion cells. The receptor fluid was removed at specific times until 48h. AMK concentration in the receptor fluids and the antimicrobial activity of the formulations were determined by a microbiologic agar-diffusion inhibition assay of the growth of test bacteria to obtain a linear relationship between diameter of the inhibition halo and AMK amount. Results showed that the release of AMK from the new formulation was considerably more prolonged (48h) than that observed for Dramigel® (24h), with AMK amount more than double in comparison with Dramigel® at the same observation time, allowing therefore a significant increased antimicrobial activity. In fact, the new formulation significantly reduced the number of bacteria two/three times more than the controls and the commercial product even after 48h. The approach of surface reservoirs of drug in the topical administration will be an interesting alternative to the existing therapeutic strategies. The achievement of a constant concentration of active ingredient on the skin for a controlled and prolonged time would allow a reduction in applications of the dermatological product, with benefits in the treatment and patient compliance.
Evaluation of amikacin sulfate activity in a topical innovative formulation against Enterobacteriaceae
Tullio V;Mandras N;Roana J;CRIVELLO, ALESSANDRA;Scalas D;Leone F;Cavalli R;
2018-01-01
Abstract
Skin infectious diseases represent a global issue costing millions of dollars per year in developed countries. Antibiotic therapy is generally considered the gold standard to treat overt infections. However, the limited efficacy of transdermal drug delivery has currently directed the researcher attention towards new approaches to improve the topical release of active principles. In this context, an interdisciplinary study was aimed to develop innovative eudermic formulations based on the use of porous biocompatible particles, inside of which amikacin sulfate (AMK) was incorporated to obtain a saturated antimicrobial drug formulation, as drug reservoir. The active ingredient is released from the pores of the particles with a mechanism similar to the drug dissolution in solution. We determined the antimicrobial efficacy and the prolonged release time of the new drug formulation (silica particles coupled to 5% AMK) in comparison with the commercial product Dramigel® 5% AMK (Morgan s.r.l,VI). The antimicrobial activity of AMK, and Dramigel® was evaluated by MIC and MBC towards Gram-negative bacteria involved in skin infections (Escherichia coli, Klebsiella pneumoniae, and Enterobacter cloacae). In vitro AMK release from the formulation and Dramigel® was determined in Franz diffusion cells. The receptor fluid was removed at specific times until 48h. AMK concentration in the receptor fluids and the antimicrobial activity of the formulations were determined by a microbiologic agar-diffusion inhibition assay of the growth of test bacteria to obtain a linear relationship between diameter of the inhibition halo and AMK amount. Results showed that the release of AMK from the new formulation was considerably more prolonged (48h) than that observed for Dramigel® (24h), with AMK amount more than double in comparison with Dramigel® at the same observation time, allowing therefore a significant increased antimicrobial activity. In fact, the new formulation significantly reduced the number of bacteria two/three times more than the controls and the commercial product even after 48h. The approach of surface reservoirs of drug in the topical administration will be an interesting alternative to the existing therapeutic strategies. The achievement of a constant concentration of active ingredient on the skin for a controlled and prolonged time would allow a reduction in applications of the dermatological product, with benefits in the treatment and patient compliance.
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