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 À20.7 and À29.3 mV. TAT/PB LID NLC (851.2 ± 25.3 mg/cm 2) showed remarkably better percutaneous penetration ability than PB LID NLC (610.7 ± 22.1 mg/cm 2), TAT LID NLC (551.9 ± 21.8 mg/cm 2) (p < .05) and nonmodified LID NLC (428.2 ± 21.4 mg/cm 2). 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.

Nanostructured Lipid Carriers for Transdermal Drug Delivery

“…The study concluded that the multi-decorated NLCs showed the most prominent anesthetic effect than single ligand decorated or undecorated LID NLC in vivo. Furthermore, this result was correlated with enhancement in skin penetration of lidocaine hydrochloride from multi-decorated NLCs (TAT/PB NLC) compared to the other formulae [57].…”

Acute myocardial infarction therapy using calycosin and tanshinone co-loaded; mitochondrion-targeted tetrapeptide and cyclic arginyl-glycyl-aspartic acid peptide co-modified lipid-polymer hybrid nano-system: preparation, characterization, and anti myocardial infarction activity assessment

“…CAL/TAN NS (200 mg) was dissolved in DMF (10 mL), EDC (20.0 mg) and NHS (12.0 mg) were added at 0 °C to activate the carboxylic acid groups of DSPE-PEG-COOH (A) (Jiang et al, 2021 ). Then MTP-131 (H-D-Arg-Dmt-Lys-Phe-NH 2 ) was dissolved in DMF (5 mL) and added dropwise to the above (A) and stirred for 24 h. The resulting solution was dialyzed (MWCO = 2 kDa) against distilled water for 24 h to get MTP-131 modified CAL/TAN NS (MTP-CAL/TAN NS).…”

Acute myocardial infarction therapy: in vitro and in vivo evaluation of atrial natriuretic peptide and triphenylphosphonium dual ligands modified, baicalin-loaded nanoparticulate system

“…A transmission electron microscope (JEOL, Tokyo, Japan) was used to visualize the surface morphology of ANP/TPP-BN-LPNs (Jiang et al., 2021 ). The particle size, polydispersity index (PDI), and zeta potential of LPNs were evaluated using dynamic light scattering (DLS) technique of NLC at room temperature on Malvern ZetaSizer Nano ZS90 (Malvern Instruments Ltd., Malvern, UK).…”