In vitro percutaneous absorption of 14C-labeled β-lactone promises topical delivery of new bacterial virulence inhibitors.
Bacterial infections of skin and soft tissue represent a major health threat, especially if they are caused by multidrug-resistant strains such as MRSA. Novel treatment options for topical application are urgently needed, and even if new drug candidates are identified, their properties must match the specific physical requirements of the skin in order to penetrate and reach the site of bacterial infection. β-Lactones have been shown to eliminate bacterial virulence, but knowledge about their potential in topical treatments had thus far been lacking. Herein we present the synthesis and in-depth investigations of skin permeation and skin distribution of a radioactive (14)C-labeled tool compound that was formulated with various basic ointments and applied to pig skin samples. Our results show that skin penetration depends highly on the nature of the formulation base. Vaseline is the most efficient ointment and is best suited for effecting maximal drug delivery within and through the stratum corneum, an important entrance barrier, and meets the required quantities for eliciting anti-virulence effects. We are confident that the nature of these new β-lactone virulence inhibitors confers applicability and potency for topical treatment, and will translate into a new formulation of this highly potent drug candidate for the treatment of skin and soft tissue infections.
AVIRU, EXIST Transfer of Research, OC II, Lichtenbergstraße 4, 85747 Garching, Germany.
Katrin
K
Lorenz-Baath
Vadim S
VS
Korotkov
Christoph
C
Lierse von Gostomski
Stephan A
SA
Sieber
D000287:Administration, Topical; D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002250:Carbon Radioisotopes / Q000737:chemistry; D002626:Chemistry, Pharmaceutical; D004337:Drug Carriers / Q000737:chemistry*; D007783:Lactones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects / Q000472:pathogenicity; D010577:Petrolatum / Q000737:chemistry; D012867:Skin / Q000378:metabolism; D012869:Skin Absorption / Q000187:drug effects*; D013552:Swine; D014774:Virulence
D000900:Anti-Bacterial Agents; D002250:Carbon Radioisotopes; D004337:Drug Carriers; D007783:Lactones; D010577:Petrolatum