Penetratin-induced transdermal delivery from H(II) mesophases of sodium diclofenac.
Penetratin, a cell penetrating peptide is embedded within a reversed hexagonal (H(II)) mesophase for improved transdermal delivery of sodium diclofenac (Na-DFC). The H(II) mesophase serves as the solubilization reservoir and gel matrix whereas penetratin is the transdermal penetration enhancer for the drug. The systems were characterized and the interactions between the components were determined by SAXS, ATR-FTIR and SD-NMR. High affinity of Na-DFC to glycerol monooleate (GMO) was revealed, associated with increasing the order within the water channels. This affinity is enhanced upon heating and seems to be associated with GMO dehydration. Penetratin (PEN) is entrapped at the hydrophilic region of the H(II) mesophase, between the GMO headgroups, reducing the order of the system and decreasing the size of the hexagonal domains. The transdermal delivery rate of Na-DFC through porcine skin, from the H(II) mesophases, was enhanced by PEN and so also the cumulative transport crossing the skin. PEN induced accelerated drug diffusion through the stratum corneum, towards the different skin layers. The transdermal delivery enhancement is explained from the results of the ATR-FTIR analysis. It seems that PEN accelerates the structural transition of skin lipids from hexagonal to liquid. The disordering results in enhanced diffusion of Na-DFC through the stratum corneum, followed by enhanced overall penetration of the drug.
The Ratner Chair of Chemistry, Casali Institute of Applied Chemistry, The Institute of Chemistry, The Hebrew University of Jerusalem, Edmond J. Safra Campus, Givat Ram, Jerusalem 91904, Israel.
Marganit
M
Cohen-Avrahami
Dima
D
Libster
Abraham
A
Aserin
Nissim
N
Garti
D000279:Administration, Cutaneous; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000493:pharmacokinetics; D002210:Caprylates / Q000737:chemistry; D002352:Carrier Proteins / Q000737:chemistry*; D057846:Cell-Penetrating Peptides; D004008:Diclofenac / Q000008:administration & dosage* / Q000493:pharmacokinetics; D004058:Diffusion; D004337:Drug Carriers / Q000737:chemistry*; D005989:Glycerides / Q000737:chemistry; D057927:Hydrophobic and Hydrophilic Interactions; D066298:In Vitro Techniques; D050866:Liquid Crystals / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008859:Microscopy, Polarization; D008956:Models, Chemical; D012867:Skin / Q000378:metabolism; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared; D034421:Sus scrofa; D014280:Triglycerides / Q000737:chemistry
D000894:Anti-Inflammatory Agents, Non-Steroidal; D002210:Caprylates; D002352:Carrier Proteins; D057846:Cell-Penetrating Peptides; D004337:Drug Carriers; D005989:Glycerides; D014280:Triglycerides; D004008:Diclofenac; C003637:tricaprylin; C414409:penetratin; C005953:monoolein