The rationale behind this work was that a permeation enhancing carrier could facilitate the transport of antibacterial molecules through the two
biological barriers: stratum corneum of the skin and bacterial membrane/cell wall. To this end,
erythromycin ethosomes (EE) were designed and characterized, and their antibacterial efficiency was evaluated in vitro and in vivo. TEM, CLSM, DLS, DSC and ultracentrifugation tests indicate that EE are small unilamellar soft vesicles encapsulating 78.6%
erythromycin. The compositions were stable for at least one year at room temperature. In live/dead viability/cytotoxicity tests, EE systems were nontoxic to cultured 3T3 dermal fibroblasts. Susceptibility studies conducted on three bacterial strains (B. subtilis ATCC 6633, S. aureus ATCC 29213 and S. aureus clinically resistant to
erythromycin) showed significantly larger inhibition zones for EE as compared to
erythromycin in hydroethanolic solutions. Moreover, EE reduced
erythromycin MIC as compared to control
solution: from 2.5 to 1.25 microg/ml for S. aureus ATCC 29213 and from 12.5 to 5.0 microg/ml for clinically isolated resistant S. aureus strain. Ethosomal
erythromycin applied to the skin of ICR mice inoculated with 10(7)cfu S. aurues ATCC 29213 resulted in complete inhibition of
infection. On the contrary, when hydroethanolic
solution of
erythromycin was applied, deep dermal and subcutaneous
abscesses developed within five days after challenge. On day seven, a similar number of S. aureus colonies (1.06x10(7) vs. 0.90x10(7) cfu/g tissue) were isolated from the untreated
wounds or treated with hydroethanolic
erythromycin. For these animals, histopathological examination showed
necrosis, destroyed skin structures and dense infiltrates of neutrophils and macrophages. These findings show that ethosomes are efficient carriers for
erythromycin delivery to bacteria localized within the deep skin strata for eradication of
staphylococcal infections.