Transdermal delivery of human growth hormone through RF-microchannels.
OBJECTIVE
To evaluate the bioavailability and bioactivity of human growth hormone (hGH) delivered transdermally through microchannels (MCs) in the skin created by radio-frequency (RF) ablation.


METHODS
The creation of MCs was observed in magnified rat and guinea pig skin after staining by methylene blue. Various doses of hGH in a dry form were applied on rat or guinea pig (GP) skin after the formation of MCs. The pharmacokinetic profile of systemic hGH in both animal models was monitored for 15 h post patch application. Bioactivity of the transdermally delivered hGH was verified by measuring IGF-I levels in hypophysectomized rats.


RESULTS
The ordered array of MCs was clearly visible in the magnified rat and guinea pig skin. The MCs were very uniform in diameter and of equal separation. Creation of MCs in the outer layers of the skin enabled efficient delivery of hGH, with a bioavailability of 75% (rats) or 33% (GPs) relative to subcutaneous (s.c.) injection with plasma profiles resembling that of s.c. injection. Elevated levels of systemic insulin-like growth factor-1 (IGF-I) were observed after transdermal delivery of hGH to hypophysectomized rats indicative of the bioactivity of the transdermally delivered hGH in vivo.


CONCLUSIONS
Formation of RF-microchannels is a well-controlled process. These MCs permitted the transdermal delivery of bioactive hGH in rats and GPs with high bioavailability.
Levin
Galit
G
TransPharma Medical, Lod 71291, Israel. galitl@transpharma.co.il
Gershonowitz
Amikam
A
Sacks
Hagit
H
Stern
Meir
M
Sherman
Amir
A
Rudaev
Sergey
S
Zivin
Inna
I
Phillip
Moshe
M
D000279:Administration, Cutaneous; D000818:Animals; D001682:Biological Availability; D016503:Drug Delivery Systems; D006168:Guinea Pigs; D019382:Human Growth Hormone / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D007279:Injections, Subcutaneous; D007334:Insulin-Like Growth Factor I / Q000032:analysis / Q000378:metabolism; D008297:Male; D008751:Methylene Blue; D011846:Radio Waves; D051381:Rats; D017207:Rats, Sprague-Dawley; D012869:Skin Absorption
D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; D008751:Methylene Blue