Topical anesthetic and pain relief using penetration enhancer and transcriptional transactivator peptide multi-decorated nanostructured lipid carriers
Tao Jiang, Shuangshuang Ma, Yangyang Shen, Yuwen Li, Ruirui Pan, Huaixin Xing
Abstract
Many strategies have been developed to overcome the stratum corneum (SC) barrier, including functionalized nanostructures. Chemical penetration enhancers (CPEs) and cell-penetrating peptides (CPP) were applied to decorate nanostructured lipid carriers (NLC) for topical anesthetic and pain relief. A novel pyrenebutyrate (PB-PEG-DSPE) compound was synthesized by the amide action of the carboxylic acid group of PB with the amido groups of DSPE-PEG. PB-PEG-DSPE has a hydrophobic group, hydrophilic group, and lipid group. The lipid group can be inserted into NLC to form PB functional NLC. In order to improve the penetrability, TAT and PB multi-decorated NLC were designed for the delivery of lidocaine hydrochloride (LID) (TAT/PB LID NLC). The therapeutic effects of NLC in terms of in vitro skin penetration and in vivo in animal models were further studied. The size of TAT/PB LID NLC tested by DLS was 153.6 ± 4.3 nm. However, the size of undecorated LID NLC was 115.3 ± 3.6 nm. The PDI values of NLC vary from 0.13 ± 0.01 to 0.16 ± 0.03. Zeta potentials of NLC were negative, between −20.7 and −29.3 mV. TAT/PB LID NLC (851.2 ± 25.3 µg/cm2) showed remarkably better percutaneous penetration ability than PB LID NLC (610.7 ± 22.1 µg/cm2), TAT LID NLC (551.9 ± 21.8 µg/cm2) (p < .05) and non-modified LID NLC (428.2 ± 21.4 µg/cm2). TAT/PB LID NLC exhibited the most prominent anesthetic effect than single ligand decorated or undecorated LID NLC in vivo. The resulting TAT/PB LID NLC exhibited good skin penetration and anesthetic efficiency, which could be applied as a promising anesthesia system.