RESUMO
Silver has been shown to improve the antibiotic effects of other drugs against both Gram- positive and -negative bacteria. In this study, we investigated the antibiotic potential of cannabidiol (CBD), cannabichromene (CBC) and cannabigerol (CBG) and their acidic counterparts (CBDA, CBCA, CBGA) against Gram-positive bacteria and further explored the additive or synergistic effects of silver nitrate or silver nanoparticles using 96-well plate growth assays and viability (CFUs- colony-forming units). All six cannabinoids had strong antibiotic effects against MRSA with minimal inhibitory concentrations (MICs) of 2 mg/L for CBG, CBD and CBCA; 4 mg/L for CBGA; and 8 mg/L for CBC and CBDA. Using 96-well checkerboard assays, CBC, CBG and CBGA showed full or partial synergy with silver nitrate; CBC, CBDA and CBGA were fully synergistic with silver nanoparticles against MRSA. Using CFU assays, combinations of CBC, CBGA and CBG with either silver nitrate or silver nanoparticles, all at half or quarter MICs, demonstrated strong, time-dependent inhibition of bacterial growth (silver nitrate) and bactericidal effects (silver nanoparticles). These data will lead to further investigation into possible biomedical applications of specific cannabinoids in combination with silver salts or nanoparticles against drug-resistant Gram-positive bacteria.
RESUMO
Hollow microneedles can overcome the stratum corneum (SC) barrier and deposit a compound directly into the viable epidermis or the dermis, unlike adhesive patches that rely on drug diffusion across the SC. The traditional one-dimensional methods used to study the diffusivity of drugs across the skin layers are not very accurate for hollow microneedles, since the ejection of compounds out of microneedle lumens resembles a point-source spreading in all directions and is highly dependent on injection depth. This paper presents a technique that is useful for studying drug injection using hollow microneedles at various depths below the SC. This technique uses confocal microscopy to image the distribution of a fluorescent compound in the skin after injection. The fluorescence distribution in the skin is observed over time and applied to a spherical Gaussian diffusion model for limited source diffusion to determine the diffusion coefficient of the compound in the skin. Applied to freshly excised pig skin, the diffusion coefficient for the anti-cancer drug doxorubicin was measured as 4.61 × 10(-9) cm(2)/s, while the diffusion coefficient in previously refrigerated or frozen pig skin was 1.31 × 10(-8) cm(2)/s and 4.21 × 10(-8) cm(2)/s, respectively. Our data suggests that skin storage conditions can substantially alter the diffusion of drugs. The use of refrigerated and, even more so, previously frozen skin should be avoided for quantitative transdermal drug delivery studies.
