Pharmacokinetics, toxicity of nasal cilia and immunomodulating effects in Sprague-Dawley rats following intranasal delivery of thymopentin with or without absorption enhancers.
Thymopentin (TP 5), a synthetic pentapeptide, has been used in clinic as a modulator for immnuodeficiencies through intramuscular administration. The objectives of this study was to investigate the pharmacokinetics using normal rats and toxicity of nasal cilia as well as immunomodulating effects using immunosuppression rats after intranasal delivery of thymopentin with or without an absorption enhancer. The absorption extent of fluorescein isothiocyanate (FITC) labeled TP 5 via nasal delivery at a single dose is significantly improved by incorporating sodium deoxycholate, Brij 35 and chitosan, respectively. FITC-TP 5 can also be absorbed to such an extent ranging from 15 to 28% after intranasal administration of FITC-TP 5 alone, FITC-TP 5 with sodium caprylate, or with bacitracin, respectively. After seven consecutive days multiple dosing, TP 5 formulation with sodium deoxycholate or Brij 35 caused apparently injury to nasal cilia, indicating these two enhancers would not be appropriate for nasal delivery. Results from superoxide dismutase activity, maleic dialdehyde, T-lymphocyte subsets (CD3+, CD4+, CD8+ and CD4+/CD8+ ratio) analyses suggest that all the selected enhancers improve the modulating effects of TP 5 in the immunosuppression rats. On an overall evaluation, intranasal TP 5 alone, TP 5 with chitosan, or TP 5 with bacitracin formulation may be suitable for the future clinical application.
Wang
Jing
J
Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Xueyuan Road 38, Beijing 100083, China.
Lu
Wan-Liang
WL
Liang
Gong-Wen
GW
Wu
Ke-Chun
KC
Zhang
Chun-Guang
CG
Zhang
Xuan
X
Wang
Jian-Cheng
JC
Zhang
Hua
H
Wang
Xue-Qing
XQ
Zhang
Qiang
Q
D000042:Absorption / Q000187:drug effects; D000281:Administration, Intranasal; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002923:Cilia / Q000187:drug effects* / Q000473:pathology; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D007108:Immune Tolerance / Q000187:drug effects*; D008297:Male; D023421:Models, Animal; D009666:Nose / Q000166:cytology* / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D016305:Thymopentin / Q000008:administration & dosage / Q000276:immunology / Q000493:pharmacokinetics* / Q000633:toxicity*
D016305:Thymopentin