Transdermal permeation enhancement of N-trimethyl chitosan for testosterone.
The aim of this study was to evaluate the transdermal permeation enhancement of N-trimethyl chitosan (TMC) with different degrees of quaternization (DQ). TMCs with DQ of 40 and 60% (TMC40 and TMC60) were synthesized and characterized by (1)H NMR. Testosterone (TS) used as an effective drug, four different gels were prepared without enhancer, with 5% TMC40, 5% TMC60 or 2% Azone, respectively as enhancer. The effect of TMC60 on the stratum corneum was studied by Attenuated Total Reflection-Fourier Transform Infrared Spectroscopy (ATR-FTIR) combined with the technique of deconvolution. The results showed that TMC60 could significantly affect the secondary structure of keratin in stratum corneum. In vitro permeation studies were carried out using Franz-diffusion cells and in vivo studies were performed in rabbits. Both in vitro and in vivo permeation studies suggested the transdermal permeation enhancement of TMCs. Compared to the TS gel without enhancer, TS gels with enhancers all showed significant enhancing effect on transdermal permeation of TS (P<0.05). Meanwhile, compared to 2% Azone, 5% TMC60 had a stronger enhancement (P<0.05) while 5% TMC40 had a similar effect (P>0.05). The results suggested that the enhancement of TMCs increased with the increase of DQ.
He
Wen
W
Department of Pharmacy of Renmin Hospital, Wuhan University, Wuhan 430060, People's Republic of China. hwzxd@163.com
Guo
Xianxi
X
Zhang
Mian
M
D000279:Administration, Cutaneous; D000818:Animals; D001381:Azepines / Q000737:chemistry; D048271:Chitosan / Q000737:chemistry*; D005079:Excipients / Q000737:chemistry*; D005782:Gels; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051379:Mice; D010539:Permeability; D011817:Rabbits; D012869:Skin Absorption; D017550:Spectroscopy, Fourier Transform Infrared; D013739:Testosterone / Q000008:administration & dosage / Q000493:pharmacokinetics*
D001381:Azepines; D005079:Excipients; D005782:Gels; C118071:N-trimethyl chitosan chloride; C035229:laurocapram; D013739:Testosterone; D048271:Chitosan