Advances in the development of antimicrobial peptides and proteins for inhaled therapy

Advances in the development of antimicrobial peptides and proteins for inhaled therapy.

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Item Type: Review
Status: Published
Official URL:
Journal or Publication Title: Advanced Drug Delivery Reviews
Volume: 180
Page Range: p. 114066
Date: 20 November 2021
Divisions: Tuberculosis
Depositing User: General Admin
Identification Number: 10.1016/j.addr.2021.114066
ISSN: 0169409X
Date Deposited: 26 Sep 2022 00:29

Antimicrobial peptides and proteins (APPs) are becoming increasingly important in targeting multidrug-resistant (MDR) bacteria. APPs is a rapidly emerging area with novel molecules being produced and further optimised to enhance antimicrobial efficacy, while overcoming issues associated with biologics such as potential toxicity and low bioavailability resulting from short half-life. Inhalation delivery of these agents can be an effective treatment of respiratory infections owing to the high local drug concentration in the lungs with lower exposure to systemic circulation hence reducing systemic toxicity. This review describes the recent studies on inhaled APPs, including in vitro and in vivo antimicrobial activities, toxicity assessments, and formulation strategies whenever available. The review also includes studies on combination of APPs with other antimicrobial agents to achieve enhanced synergistic antimicrobial effect. Since different APPs have different biological and chemical stabilities, a targeted formulation strategy should be considered for developing stable and inhalable antimicrobial peptides and proteins. These strategies include the use of sodium chloride to reduce electrostatic interaction between APP and extracellular DNA in sputum, the use of D-enantiomers or dendrimers to minimise protease-mediated degradation and or the use of prodrugs to reduce toxicity. Although great effort has been put towards optimising the biological functions of APPs, studies assessing biological stability in inhalable aerosols are scarce, particularly for novel molecules. As such, formulation and manufacture of inhalable liquid and powder formulations of APPs are underexplored, yet they are crucial areas of research for clinical translation.

Wang, Yuncheng
Chang, Rachel Yoon Kyung
Britton, Warwick J.
Chan, Hak-Kim
Last Modified: 26 Sep 2022 00:29

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