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Novel skin permeation enhancers based on amino acid ester ionic liquid: Design and permeation mechanism
- Source :
- International journal of pharmaceutics. 576
- Publication Year :
- 2019
-
Abstract
- This study developed novel ionic liquids (ILs) based on amino acids. We first screened 15 methyl amino acid ester hydrochlorides ([AAC1]Cl) for their skin permeation enhancements using 5-Fluorouracil (5-Fu) and Hydrocortisone (HC) as model drugs. Glycine methyl ester hydrochloride ([GlyC1]Cl), L-proline methyl ester hydrochloride ([L-ProC1]Cl), and L-leucine methyl ester hydrochloride ([L-LeuC1]Cl) were selected, and their ester sites were modified with different carbon chains (C8 and C12). The resulting ILs showed improved permeation to the two drugs. TEWL and CLSM assays revealed the moderation effects of the modified ILs on skin barrier function, whereas L-proline dodecyl ester hydrochloride ([ProC12]Cl) and L-leucine dodecyl ester hydrochloride ([L-LeuC12]Cl) exhibited the strongest activities. Permeation mechanisms were further investigated by ATR-FTIR, solid-NMR, SEM, and TEM analyses. The results suggested that [L-ProC12]Cl and [L-LeuC12]Cl combined the advantages of amino acid esters and IL solvent and could interact with the intercellular lipid domain by the multi-functions of lipid fluidization and lipid extraction, which were observed in a dosage- and time-dependent manner. Additionally, pathological examination suggested that the amino acid ester-based ILs (AAE-ILs) had good biocompatibility. In conclusion, this study has generated novel chemical penetration enhancers (CPEs) based on AAE-ILs and may be potentially utilized in drug transdermal delivery systems (TDDSs).
- Subjects :
- Biocompatibility
Hydrocortisone
Drug Compounding
Skin Absorption
Pharmaceutical Science
Ionic Liquids
02 engineering and technology
Administration, Cutaneous
030226 pharmacology & pharmacy
Permeability
03 medical and health sciences
chemistry.chemical_compound
Mice
0302 clinical medicine
Animals
Amino Acids
Rats, Wistar
Enhancer
Transdermal
Skin
chemistry.chemical_classification
Chemistry
Esters
Penetration (firestop)
Permeation
021001 nanoscience & nanotechnology
Water Loss, Insensible
Amino acid
Solvent
Ionic liquid
Fluorouracil
0210 nano-technology
Nuclear chemistry
Subjects
Details
- ISSN :
- 18733476
- Volume :
- 576
- Database :
- OpenAIRE
- Journal :
- International journal of pharmaceutics
- Accession number :
- edsair.doi.dedup.....27c0b1b8497f25531906a0dcb448a0db