Purpose: For the topical anesthetic, transcriptional transactivator peptide (TAT) modified lidocaine (LID) loaded nanostructured lipid carriers (TAT-NLCs-LID) were prepared and then used for improving transdermal delivery of local anesthetic drug. Methods: In this study, TAT was conjugated with Distearoyl phosphatidylethanolamine-(polyethylene glycol) 2000 -maleimide (DSPE-PEG 2000 -Mal) to obtain TAT-PEG 2000 -DSPE. TAT-NLCs-LID were successfully prepared and characterized by determination of their particle size, morphology, drug encapsulation efficiency and in vitro drug release behavior. The skin permeation of LID-LNPs was examined using a Franz diffusion cell mounted with depilated mouse skin in vitro and in vivo anesthesia effect was evaluated on mice.
Results:The results showed that TAT-NLCs-LID have substantially small mean diameter (157.9 nm) and high encapsulation efficiency (81.8%). From the in vitro skin permeation results, transdermal flux of TAT-NLCs-LID was about several times higher than that of LID solution and NLCs-LID. In vivo anesthesia effect evaluation illustrated that TAT-NLCs-LID can enhance the transdermal delivery of LID by reducing the pain threshold in mice. Conclusion: These results indicate that the novel TAT containing drug delivery system is very useful for overcoming the barrier function of the skin and could deliver anesthetic through the skin. TAT-NLCs-LID could function as promising topical anesthetic system.
In order to investigate the effects of transient receptor potential channel A1 (TRPA1)-mediated neurogenic inflammatory reaction on the process of ventilator-induced lung injury (VILI). A rat VILI model was created, and the TRPA1 selective antagonist, HC-030031, was used to investigate the role of TRPA1 in the process of VILI. 50 rats were randomly divided into five groups: vehicle group, low tidal volume group, high tidal volume group, low tidal volume group with TRPA1 inhibitor, high tidal volume group with TRPA1 inhibitor. Biochemical index of lung injury in each group were determined, including the W/D ratio, total protein, count of WBC, content of MDA, activities of MPO and SOD, content of IL-8, TNF-α and substance P. Results showed that TRPA1 inhibitor could significantly reduce the inflammatory response and generation of reactive oxygen species, improve SOD activity and inhibit the production of inflammatory factors in lung tissues. TRPA1 was expressed in vagal nerve afferents, and the TRPA1 antagonist significantly inhibited the expression of substance P, indicating the involvement of TRPA1 in neurogenic inflammation. In conclusion, TRPA1 might be involved in the pathophysiological process of VILI by inducing the neurogenic inflammation, and TRPA1 inhibitor could inhibit inflammatory response of VILI.
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