Nasal delivery of recombinant human growth hormone: in vivo evaluation with Pheroid technology and N-trimethyl chitosan chloride.
OBJECTIVE
It was the aim of this study to investigate the possible enhancement of the absorption of recombinant human growth hormone (rhGH) in the nasal cavity, in the presence of a polymeric absorption enhancer, N-trimethyl chitosan chloride (TMC) and a fatty acid-based delivery system, Pheroid.


METHODS
Two types of Pheroid formulations, Pheroid vesicles and Pheroid microsponges were characterized and evaluated with regard to particle size and morphology. In vivo bioavailability studies in rats were performed and the nasal bioavailability of Pheroid vesicles and Pheroid microsponges were compared relative to subcutaneous administration. The results were also compared with different N-trimethyl chitosan chloride (TMC) formulations, TMC H-L and TMC H-H, well studied absorption enhancers.


RESULTS
Pheroid vesicles and Pheroid microsponges showed a size distribution of approxiamately 2-3 microm and 3-4 microm for Pheroid vesicles and Pheroid microsponges respectively. Using specific RIA, the relative bioavailability of rhGH after comparison with subcutaneous injection was determined to be 38.9, 128.5, 39.9, 136.3, and 8.3 % for Pheroid microsponges, Pheroid vesicles, TMC H-H, TMC H-L and control group (intranasal rhGH alone), respectively. All the enhancers showed significant absorption enhancement (P < 0.05) with the highest effect observed with TMC H-L.


CONCLUSIONS
All the enhancers may have promising potential as safe and effective nasal absorption enhancers of rhGH.
Steyn
Dewald
D
Unit for Drug Research and Development, North-West University, Potchefstroom 2531, South Africa.
du Plessis
Lissinda
L
Kotzé
Awie
A
D000281:Administration, Intranasal; D000818:Animals; D001682:Biological Availability; D048271:Chitosan / Q000737:chemistry*; D005079:Excipients / Q000737:chemistry*; D005227:Fatty Acids / Q000737:chemistry*; D019382:Human Growth Hormone / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006801:Humans; D007279:Injections, Subcutaneous; D008297:Male; D010316:Particle Size; D051381:Rats; D017207:Rats, Sprague-Dawley
D005079:Excipients; D005227:Fatty Acids; C118071:N-trimethyl chitosan chloride; D019382:Human Growth Hormone; D048271:Chitosan