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 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. _______________________________________________________________________________________

Biologics: the role of delivery systems in improved therapy

“…Pheroid technology consists of a unique submicron emulsion based on essential fatty acids. Pheroid vesicles and microsponges have been studied for nasal delivery of human growth factor and have showed promising absorption enhancement in a rat model, although not yet superior to chitosan-based absorption enhancers 35. Similar observations were made when the same technology was employed to deliver calcitonin both nasally and orally.…”

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“…60 Results showed extremely high bioavailability of Pheroid vesicle and TMC H-L (high molecular weight with low degree of quaternization) in rats, 128.5% and 136.1%, respectively.…”

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