A comprehensive review of advanced nasal delivery: Specially insulin and calcitonin

Peptide drugs through nasal mucous membrane, such as insulin and calcitonin have been widely used in the medical field. There are always two sides to a coin. One side, intranasal drug delivery can imitate the secretion pattern in human body, having advantages of physiological structure and convenient use. Another side, the low permeability of nasal mucosa, protease environment and clearance effect of nasal cilia hinder the intranasal absorption of peptide drugs. Researchers have taken multiple means to achieve faster therapeutic concentration, lower management dose, and fewer side effects for better nasal preparations. To improve the peptide drugs absorption, various strategies had been explored via the nasal mucosa route. In this paper, we reviewed the achievements of 18 peptide drugs in the past decade about the perspectives of the efficacy, mechanism of enhancing intranasal absorption and safety. The most studies were insulin and calcitonin. As a result, absorption enhancers, nanoparticles (NPs) and bio-adhesive system are the most widely used. Among them, chitosan (CS), cell penetrating peptides (CPPs), tight junction modulators (TJMs), soft NPs and gel/hydrogel are the most promising strategies. Moreover, two or three strategies can be combined to prepare drug vectors. In addition, spray freeze dried (SFD), self-emulsifying nano-system (SEN), and intelligent glucose reaction drug delivery system are new research directions in the future.