Red blood cell-mimicking liposomes loading curcumin promote diabetic wound healing.

The excessive inflammatory response is known to be a major challenge for diabetic wound healing, while bacteria secreted toxin, α-hemolysin (Hlα), was recently reported to prolong inflammation and delay diabetic wound healing. In this study, we designed a red blood cell membrane (RBCM)-mimicking liposome containing curcumin (named RC-Lip) for the treatment of diabetic wounds. RC-Lips were successfully fabricated using the thin film dispersion method, and the fusion of RBC membrane with the liposomal membrane was confirmed via surface protein analysis. RC-Lips efficiently adsorbed Hlα, thereby reducing the damage and pro-apoptotic effects of Hlα on keratinocytes. Furthermore, they remarkably facilitated liposome uptake into macrophages with advanced curcumin release and regulation of M2 macrophage polarization. In a diabetic mouse and infected wound model, RC-Lips treatment significantly promoted wound healing and re-epithelialization while downregulating interleukin-1ß (IL-1ß) and upregulating interleukin-10 (IL-10). In summary, the results showed that the spongiform RC-Lips effectively modulate the inflammatory response after adsorbing Hlα and regulating M2 macrophage polarization, leading to a significant promotion of wound healing in diabetic mice. Hence, this study provides a prospective strategy of efficiently mediating inflammatory response for diabetic wounds.

Molecular Characteristics and Genetic Analysis of Extensively Drug-Resistant Isolates with different Tn3 Mobile Genetic Elements.

Extensively drug-resistant (XDR) bacteria are the main caues for causing clinical infectious diseases. Our aim was to distinguish the present molecular epidemiological situation of XDR Klebsiella pneumoniae, Acinetobacter baumannii, and Escherichia coli isolates recovered from local hospitals in Changzhou. Antibiotic susceptibility and phenotypic analysis, multilocus sequence typing and Pulsed Field Gel Electrophoresis were performed to trace these isolates. Resistant phenotype and gene analysis from 29 XDR strains demonstrated that they mainly included TEM, CTX-M-1/2, OXA-48, and KPC products. A. baumannii strains belonged to sequence type (ST) ST224, and carrying the blaCTX-M-2/TEM gene. The quinolone genes aac(6')-ib-cr and qnrB were carrying only in A. baumannii and E.coli. Three (2.3%) of these strains were found to contain the blaNDM-1 or blaNDM-5 gene. A new genotype of K. pneumoniae was found as ST2639. Epidemic characteristics of the XDR clones showed that antibiotic resistance genes distributed unevenly in different wards in Changzhou's local hospitals. With the sequencing of blaNDM carrying isolates, the plasmids often carrying a highly conservative Tn3-relavent mobile genetic element. The especially coupled insert sequence ISKox3 may be a distinctive resistance gene transfer loci. The genotypic diversity variation of XDRs suggested that tracking and isolating the sources of antibiotic resistance especially MBL-encoding genes such as blaNDM-will help manage the risk of infection by these XDRs.

Investigation of ß-caryophyllene as terpene penetration enhancer: Role of stratum corneum retention.

Terpenes are usually used as penetration enhancers (PE) for transdermal drug delivery (TDD) of various molecules. However, TDD of hydrophilic macromolecules is becoming an urgent challenge due to their potent activities. The aim of this study was to investigate the potential application of ß-caryophyllene (ß-CP), a sequiterpene, as PE for TDD of hydrophilic macromolecules for the first time. Commonly used PEs, namely azone and 1,8-cineole (1,8-CN), were applied as controls. Transepidermal water loss (TEWL) analysis revealed that the reduction of skin barrier function caused by ß-CP was reversible. Transdermal experiments showed that when skin was treated with ß-CP or azone, there was a significant permeation-enhancing effect on fluorescein isothiocyanate (FITC) and FITC-dextran with different molecular weight (MW) of 4k or 10k. CLSM analysis confirmed that ß-CP and azone can facilitate the penetration of FD-4k through epidermis and dermis. However, the cytotoxicity of azone against epidermal keratinocytes was significantly higher than ß-CP and 1,8-CN. Additionally, application of ß-CP and 1,8-CN didn't increase erythema index (EI) but the EI values of azone group increased significantly and irreversibly, indicating the high biocompatibility of the natural terpenes. ß-CP had better permeation-enhancing effect and higher stratum corneum (SC) retention than 1,8-CN due to its increased carbon chain length and lipophilicity, as further demonstrated by molecular dynamics (MD) simulation studies. Skin electrical resistance (SER) and attenuated total reflection fourier transform infrared spectroscopy (ATR-FTIR) studies revealed a significant interfering effect of ß-CP on SC lipids. Taken together, ß-CP exhibited significant penetration enhancement of hydrophilic macromolecules due to its SC retention and SC lipid fluidization ability.