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

Drug Delivery

Hui Zhang¹  Xiaomei Zhuang¹  Xiang Gao¹  Aiping Zheng¹  Jing Gao¹  Zengming Wang¹  Yimeng Du¹  Nan Liu¹  Dan Wang¹  Xiaolu Han¹  Meng Li¹  Wenpeng Zhang¹ 

[1] State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology;

关键词: parathyroid hormone (1-34);    intranasal formulation;    permeation enhancer;    mucosal toxicity;    pharmacokinetics;   

DOI  :  10.1080/10717544.2021.1889718

来源: DOAJ

【 摘 要 】

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 in vitro 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.

【 授权许可】

Unknown