Skin infectious diseases represent a global issue costing millions of dollars per year in developed countries. Antibacterial therapies are generally considered the gold standard to treat overt infections. However, the limited efficacy of transdermal drug delivery are currently driving the attention of researchers towards new approaches to improve the topical release of active principles. In this context, an interdisciplinary study (Politecnico of Torino, Drug Science and Technology Dept., Public Health & Pediatrics Dept.) was aimed to develop innovative eudermic formulations based on reservoir of antimicrobial drugs (i.e. amikacin, AMK), allowing a sustained and prolonged release. The study is based on the use of porous biocompatible particles (i.e. silica), inside of which the active antimicrobial drug is incorporated. The active ingredient is released from the pores of the particles with a mechanism similar to the drug dissolution in solution. The technology is protected by a European patent (Eudermic compositions,WO2012/007906) owned to the Politecnico of Torino. The role of Politecnico of Torino and the Drug Science and Technology Dept. was the engineering of the reservoir that is the synthesis of porous particles, the incorporation of the drug and the characterization of the final system. The role of the research group of the Public Health & Pediatrics Dept. was to determine the antimicrobial efficacy and the prolonged release time of the new formulation (silica particles coupled to 5% AMK) in comparison with the commercial product Dramigel 5% AMK (Morgan, VI).The antimicrobial activity of AMK saturated formulation, and Dramigel was evaluated by MIC and MBC towards the main Gram negative bacteria involved in skin infections.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 was 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. 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. 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.
Innovative formulation for topic antimicrobial drug release against Gramnegative bacteria
V. Tullio;J. Roana;N. Mandras;CRIVELLO, ALESSANDRA;D. Scalas;F. Leone;R. Cavalli;
2017-01-01
Abstract
Skin infectious diseases represent a global issue costing millions of dollars per year in developed countries. Antibacterial therapies are generally considered the gold standard to treat overt infections. However, the limited efficacy of transdermal drug delivery are currently driving the attention of researchers towards new approaches to improve the topical release of active principles. In this context, an interdisciplinary study (Politecnico of Torino, Drug Science and Technology Dept., Public Health & Pediatrics Dept.) was aimed to develop innovative eudermic formulations based on reservoir of antimicrobial drugs (i.e. amikacin, AMK), allowing a sustained and prolonged release. The study is based on the use of porous biocompatible particles (i.e. silica), inside of which the active antimicrobial drug is incorporated. The active ingredient is released from the pores of the particles with a mechanism similar to the drug dissolution in solution. The technology is protected by a European patent (Eudermic compositions,WO2012/007906) owned to the Politecnico of Torino. The role of Politecnico of Torino and the Drug Science and Technology Dept. was the engineering of the reservoir that is the synthesis of porous particles, the incorporation of the drug and the characterization of the final system. The role of the research group of the Public Health & Pediatrics Dept. was to determine the antimicrobial efficacy and the prolonged release time of the new formulation (silica particles coupled to 5% AMK) in comparison with the commercial product Dramigel 5% AMK (Morgan, VI).The antimicrobial activity of AMK saturated formulation, and Dramigel was evaluated by MIC and MBC towards the main Gram negative bacteria involved in skin infections.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 was 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. 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. 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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