Needleless administration of advanced therapies into the skin via the appendages using a hypobaric patch.

Advanced therapies are commonly administered via injection even when they act within the skin tissue, and this increases the chances of off-target effects. Here we report the use of a skin patch containing a hypobaric chamber that induces skin dome formation to enable needleless delivery of advanced therapies directly into porcine, rat, and mouse skin. Finite element method modeling showed that the hypobaric chamber in the patch opened the skin appendages by 32%, thinned the skin, and compressed the appendage wall epithelia. These changes allowed direct delivery of an H1N1 vaccine antigen and a diclofenac nanotherapeutic into the skin. Fluorescence imaging and infrared mapping of the skin showed needleless delivery via the appendages. The in vivo utility of the patch was demonstrated by a superior immunoglobulin G response to the vaccine antigen in mice compared to intramuscular injection and a 70% reduction in rat paw swelling in vivo over 5 h with diclofenac without skin histology changes.

New insights into eutectic cream skin penetration enhancement.

The manner in which the eutectic cream EMLA enhances the percutaneous penetration of lidocaine and prilocaine into human skin is still not fully understood. The purpose of this study was to investigate if the modification of drug aggregation played a role in the way EMLA facilitates delivery. Light scattering analysis of lidocaine alone in water gave a critical aggregation concentration (CAC) of 572 µM and a mean aggregate size of 58.8 nm. The analysis of prilocaine in identical conditions gave a CAC of 1177 µM and a mean aggregate size of 105.7 ± 24.8 nm. When the two drugs were mixed at their eutectic 1:1 ratio in water the CAC reduced to 165.8 µM and the aggregate size was 43.82 nm. This lidocaine-prilocaine interaction in water was further modified upon addition of polyoxyethylene hydrogenated castor oil, the surfactant in the EMLA aqueous phase, to produce aggregates of <20 nm. The physical characterisation data suggested that it was the EMLA cream's surfactant that modified the drug molecular interactions in the aqueous continuous phase and caused a 6 fold higher drug penetration through human epidermal tissue compared to the oil formulations tested in this study.

Microbial diagnosis of infection and colonization of cardiac implantable electronic devices by use of sonication.

OBJECTIVES: The clinical utility of sonication as an adjunctive diagnostic tool for the microbial diagnosis of cardiac implantable device-associated infections (CIDAIs) was investigated. METHODS: The implants of 83 subjects were investigated, 15 with a CIDAI and 68 without a clinical infection. Clinical data were analyzed prospectively and sonication fluid cultures (83 patients, 100%) and traditional cultures (31 patients, 37.4%) were performed RESULTS: Generator pocket infection and device-related endocarditis were found in 13 (86.7%) and four (26.7%) subjects, respectively. The mean numbers of previous technical complications and infections were higher in the infected patients compared to the non-infected patients (8 vs. 1, p<0.001; 2 vs. 0, p<0.031, respectively). The sensitivity and specificity for detecting CIDAI was 73.3% (11/15) and 48.5% (33/68) for sonication fluid culture, and 26.7% (4/15) and 100% (16/16) for traditional culture (p<0.001), respectively. A higher number of organisms were identified by sonication fluid than by tissue culture (58 vs. 4 specimens; p<0.001). The most frequent organisms cultured were Gram-positive cocci (66.1%), mainly coagulase-negative staphylococci (35.5%). Thirty-five (51.5%) non-infected subjects were considered colonized due to the positive identification of organisms exclusively through sonication fluid culture. CONCLUSIONS: Sonication fluid culture from the removed cardiac implants has the potential to improve the microbiological diagnosis of CIDAIs.