Topical anesthetic and pain relief using penetration enhancer and transcriptional transactivator peptide multi-decorated nanostructured lipid carriers.

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.

• Authors: Tao Jiang, Shuangshuang Ma, Yangyang Shen, Yuwen Li, Ruirui Pan, Huaixin Xing
• Journal: Drug delivery (Drug Deliv) Vol. 28 Issue 1 Pg. 478-486 (Dec 2021) ISSN: 1521-0464 [Electronic] England
• PMID: 33641554 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Anesthetics, Local
• Cell-Penetrating Peptides
• Drug Carriers
• Excipients
• Lipids
• Lidocaine

Topics

• Administration, Cutaneous
• Anesthetics, Local (administration & dosage, pharmacokinetics, pharmacology)
• Animals
• Cell-Penetrating Peptides (chemistry)
• Disease Models, Animal
• Drug Carriers (chemistry)
• Drug Delivery Systems
• Excipients (chemistry)
• Lidocaine (administration & dosage, pharmacokinetics, pharmacology)
• Lipids (chemistry)
• Mice
• Nanostructures
• Pain (drug therapy)
• Rats
• Rats, Wistar
• Skin Absorption