Development and in vivo 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(R) HS.15 were compared as permeation enhancers. The mechanisms of action of citric acid and Kolliphor(R) HS.15 were investigated using an in vitro model of nasal mucosa, and Kolliphor(R) 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(R) HS.15 did not cause obvious mucosa damage. Finally, Kolliphor(R) 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(R) 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(R) HS.15 as a permeation enhancer. Intranasal formulations with higher concentrations of Kolliphor(R) HS.15 for higher bioavailability of PTH(1-34) could be further researched.

Automated summary

Efforts were made to develop an effective and biosafe intranasal formulation for parathyroid hormone (1-34), with 10% Kolliphor(R) HS.15 identified as a permeation enhancer that significantly increased the bioavailability of PTH(1-34). Further research on intranasal formulations with higher concentrations of Kolliphor(R) HS.15 for enhanced bioavailability of PTH(1-34) could be considered.