Transcriptional transactivator peptide modified lidocaine-loaded nanoparticulate drug delivery system for topical anesthetic therapy

Abstract

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.

A Phage Lysin Fused to a Cell-Penetrating Peptide Kills Intracellular Methicillin-Resistant Staphylococcus aureus in Keratinocytes and Has Potential as a Treatment for Skin Infections in Mice

“…Previously, we revealed that CPP Tat -JDlys is capable of penetrating the membrane of keratinocytes to eliminate intracellular bacteria. Wang et al revealed that a cell-penetrating peptide (which has an amino acid sequence similar to that of CPP Tat ) could deliver the drug through the skin and thus overcome the barrier function of the skin (35). So, we suspect that CPP Tat helped JDlys gain access to deeper tissue layers and prevent the skin damage caused by MRSA, although subcutaneous therapy is a complicated process involving integrated tissue consisting of numerous cell types besides keratinocytes.…”

A novel local anesthetic system: transcriptional transactivator peptide-decorated nanocarriers for skin delivery of ropivacaine

“…Furthermore, Wang et al20 reported that TAT-conjugated and octadecyl-quaternized lysine-modified chitosan polymeric liposomes effectively enhanced skin permeation, thus achieving rapid and effective local transdermal anesthetics. More recently, Wang et al21 used TAT-modified NCs to enhance transepidermal delivery of lidocaine on the mice model and found that the system was useful for overcoming the skin barrier and delivering anesthetic through the skin.…”

<p>An efficient and long-acting local anesthetic: ropivacaine-loaded lipid-polymer hybrid nanoparticles for the control of pain</p>

“…Size and PDI of the NPs are important factors for the nanocarriers, which can influence the distribution of carriers. 37 Particle sizes lower than 200 nm (with a PDI lower than 0.2) could decrease the uptake by the liver, prolong circulation time in the blood, and improve bioavailability. The particle size and PDI of RPV-LPNs were 112.3±2.6 nm and 0.16±0.02; the similar size and PDI found on E-LPNs indicated the encapsulation of RPV had negligible effect on the system.…”