Probing Dynamic Behavior of Chemical Enhancers Passing In and Out of the Stratum Corneum and Modulation by Biodegradable Enhancer.

Chemical enhancers (CEs) decreased the barrier of the stratum corneum (SC) to enhance drug permeation. This was a "dynamic" behavior, which involved three processes including passing in, acting on, and passing out of the SC. However, compared with mature "static" researches about acting on the SC, the other two processes were poorly understood. This work aimed to probe the dynamic behavior of CEs and modulate it for satisfactory effectiveness. The investigating method of CEs' dynamic behavior was established to obtain the rate of CEs passing in and out of the SC. An analysis attribution was conducted to obtain the possible reasons for the quite different dynamic behavior of CEs based on log P, solubility parameter, and minimum binging energy. It demonstrated the rate of CEs passing in and out of the SC was dependent on CE affinity with the SC and the interaction between CEs and the SC, respectively. The relevance between CEs' dynamic behavior and the extent of decreasing SC barrier was confirmed by transepidermal water loss (TEWL). The higher rate of CE passing in the SC and a lower rate of passing out of the SC may contribute to an increased concentration of CEs in the SC, leading to a stronger ability to decrease the SC barrier. More importantly, two biodegradable CEs (Leu-Dod and Ser-Dod) of dodecanol were synthesized and achieved a modulation of its dynamic behavior to obtain more satisfactory effectiveness of enhancing drug permeation. This work was meaningful for the guidance of rationally promoting CEs' effectiveness from a dynamic perspective, which was an unprecedented attempt in this field.

Modified internal curvilinear distraction device with a pre-embedding guide rail, drive screw, and universal joint for curvilinear lengthening of the mandible: A finite element analysis and animal experiment.

OBJECTIVES: The semiburied design of the traditional internal distractor has a relatively high risk of infection and aesthetic problems. To reduce these potential risks, a modified internal distractor with design of pre-embedding curvilinear rail, drive screw, and universal joint was invented. Its stress distribution characteristics and the effect on curvilinear distraction osteogenesis (DO) in vivo were further tested. MATERIALS AND METHODS: Finite element analysis (FEA) was performed on a model of the human mandible and distraction device to measure the stress distribution during curvilinear DO. Six beagles underwent curvilinear DO and consolidation using the new device. Radiological and histological examinations were performed on the new bone. RESULTS: On FEA, the stress was concentrated in the condyle (128.6 MPa) and curved guide rails (324.8 MPa). Four of the six animals completed the DO period and were consolidated for 12 weeks. Secondary infections were not observed. Radiography showed that a new fan-shaped bone-15.5 ± 5.5 mm in length and 4.6 ± 1.6 mm in height-was formed in the bone gap. Micro-computed tomography and histological examinations of specimens indicated that the structure of the new bone was similar to that of the normal bone. CONCLUSIONS: The modified internal curvilinear distraction device meets the mechanical strength requirement and achieve curvilinear DO in animal experiments.

Uptake pathways of phthalates (PAEs) into Chinese flowering cabbage grown in plastic greenhouses and lowering PAE accumulation by spraying PAE-degrading bacterial strain.

Uptake pathway and accumulation variation of soil and airborne phthalates (PAEs) in plastic greenhouses by vegetables remains unclear. Here, pot experiments of Chinese flowering cabbage were designed to distinguish root or leaf uptake pathways of PAEs, and investigate the mitigation of spraying PAE-degrading strain in PAE accumulation by vegetables. The results showed that leaves of Chinese flowering cabbage grown in plastic greenhouses absorbed more PAEs from air than those of outside greenhouses. Airborne PAEs were mainly stored in leaf surfaces of vegetables grown inside greenhouse, while PAEs absorbed by roots from soil were translocated and mainly stored in mesophyll, especially in cell walls and organelles. PAE concentrations in mesophyll elevated with increasing soil PAE levels, whereas those in leaf surfaces were not influenced by soil PAE levels. The values of bioconcentration factors for leaves inside greenhouses were significantly (1.39-3.47 fold) higher than those outside. PAE-degrading strain (Rhodococcus pyridinivorans XB) sprayed on leaf surfaces could grow well and Rhodococcus was the dominant genus as confirmed by Illumina high-throughput sequencing. PAE-degrading strain effectively reduced PAEs by 12.9%-34.9% in leaf surface, but not those in vegetables grown in high-PAE soil. This study demonstrated mitigation of spraying PAE-degrading strain in PAE accumulation by vegetable leaves from air of plastic greenhouse.

A pH-Responsive Host-guest Nanosystem Loading Succinobucol Suppresses Lung Metastasis of Breast Cancer.

Cancer metastasis is the leading reason for the high mortality of breast cancer. Herein, we report on a pH-responsive host-guest nanosystem of succinobucol (PHN) with pH-stimuli controlled drug release behavior to improve the therapeutic efficacy on lung metastasis of breast cancer. PHN was composed of the host polymer of ß-cyclodextrin linked with multiple arms of N,N-diisopropylethylenediamine (ßCD-DPA), the guest polymer of adamantyl end-capped methoxy poly(ethylene glycol) (mPEG-Ad), and the active agent of succinobucol. PHN comprises nanometer-sized homogenous spherical particles, and exhibits specific and rapid drug release in response to the intracellular acidic pH-stimuli. Then, the anti-metastatic efficacy of PHN is measured in metastatic 4T1 breast cancer cells, which effectively confirms the superior inhibitory effects on cell migration and invasion activities, VCAM-1 expression and cell-cell binding of RAW 264.7 to 4T1 cells. Moreover, PHN can be specifically delivered to the sites of metastatic nodules in lungs, and result in an obviously improved therapeutic efficacy on lung metastasis of breast cancer. Thereby, the pH-responsive host-guest nanosystem can be a promising drug delivery platform for effective treatment of cancer metastasis.