Development and evaluation of intranasal formulations of parathyroid hormone (1-34).

For efficient intranasal transport of parathyroid hormone (1-34) [PTH(1-34)], there is a great medical need to investigate permeation enhancers for intranasal formulations. In this study, the development of PTH(1-34) intranasal formulations was conducted. Based on conformation and chemical stability studies, the most preferable aqueous environment was determined to be 0.008 M acetate buffer solution (ABS). Subsequently, citric acid and Kolliphor HS·15 were compared as permeation enhancers. The mechanisms of action of citric acid and Kolliphor HS·15 were investigated using an model of nasal mucosa, and Kolliphor HS·15 led to higher permeability of fluorescein isothiocyanate-labeled PTH(1-34) (FITC-PTH) by enhancing both the transcellular and paracellular routes. Moreover, citric acid showed severe mucosal toxicity resulting in cilia shedding, while Kolliphor HS·15 did not cause obvious mucosa damage. Finally, Kolliphor HS·15 was studied as a permeation enhancer using a liquid chromatography tandem mass spectrometry (LC-MS/MS) method. The results showed that 5% and 10% Kolliphor HS·15 increased the bioavailability of PTH(1-34) to 14.76% and 30.87%, respectively. In conclusion, an effective and biosafe PTH(1-34) intranasal formulation was developed by using 10% Kolliphor HS·15 as a permeation enhancer. Intranasal formulations with higher concentrations of Kolliphor HS·15 for higher bioavailability of PTH(1-34) could be further researched.