Nasal delivery of recombinant human growth hormone: In vivo evaluation with pheroid™ technology and N-trimethyl chitosan chloride
Journal of Pharmacy and Pharmaceutical Sciences
Unit for Drug Research and Development, North-West University, Potchefstroom 2531, South Africa
Purpose. 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 patented 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 approximately 2-3 μm and 3-4 μm 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. Conclusion. All the enhancers may have promising potential as safe and effective nasal absorption enhancers of rhGH. The Pheroid delivery system is a novel patented system consisting of a unique submicron emulsion type formulation. The system, which consist mainly of essential fatty acids can entrap and transport pharmacological active compounds. In this study it is shown that two types of Pheroid formulations, Pheroid vesicles and Pheroid microsponges, have the ability to entrap recombinant human growth hormone and improve the nasal absorption and thus bioavailability of rhGH. Intranasal administration of rhGH entrapped in Pheroid technology is an attractive alternative to subcutaneous of intravenous administration.
drug carrier; human growth hormone; n trimethyl chitosan chloride; unclassified drug; animal experiment; area under the curve; article; controlled study; drug absorption; drug bioavailability; drug blood level; drug delivery system; drug formulation; in vivo study; male; maximum plasma concentration; morphology; nonhuman; nose cavity; particle size; rat; time to maximum plasma concentration; Administration, Intranasal; Animals; Biological Availability; Chitosan; Excipients; Fatty Acids; Human Growth Hormone; Humans; Injections, Subcutaneous; Male; Particle Size; Rats; Rats, Sprague-Dawley