Low Drug Loading Hampers the Clinical Translation of Peptide Drugs-Containing Metered-Dose Inhalers.

Peptide-based drugs have attracted extensive attention from the medical and pharmaceutical industry because of their relatively high safety and efficacy. However, most of the peptide drugs approved are administrated by injection, which can easily cause poor patient compliance. In this circumstance, pulmonary administration as an alternative to injection administration can not only avoid the above issue but also accelerate the absorption rate of peptide drugs and improve bioavailability. Among the pulmonary delivery systems available on the market, metered-dose inhalers (MDIs) have emerged as appealing candidates for pulmonary delivery systems with clinical translational value, owing to their many merits, including portable, easy-to-operate, and cost-effective properties. Nevertheless, the industrialization of peptide drugs-containing MDIs encounters a bottleneck of low drug loading, owing to the incompatibility between the propellant and the peptide drugs, which cannot be effectively overcome by the current carrier particle encapsulation strategy. Herein, we put forward the following strategies: (1) To screen amphiphilic materials with high surface activity and strong interaction with peptide drugs; (2) To construct a chemical connection between peptide drugs and amphiphilic substances; (3) To optimize the cosolvent for dispersing peptide drugs. We suppose these strategies have the potential to defeat the bottleneck problem and provide a new idea for the industrialization of peptide drugs-containing MDIs.