Nasal Delivery of Recombinant Human Growth Hormone: In Vivo Evaluation with Pheroid™ Technology and N-Trimethyl Chitosan Chloride

Abstract

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 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 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.