Hak-Kim Chan
The University of Sydney
Advanced Drug Delivery Group
Hak-Kim Chan, Professor in Pharmaceutics, is leading the Advanced Drug Delivery Group at the Sydney Pharmacy School, University of Sydney, Australia. He worked as a scientist at Genentech Inc developing inhalation protein products. His research focuses on inhalation drug formulation and delivery, ranging from small molecule drugs, to proteins, nucleic acids and bacteriophages. He played a pivotal role in the development of inhaled mannitol products Aridol™ and Bronchitol™ (both approved by the FDA) for bronchoprovocation and mucus clearance, respectively.
Affiliations: (1). Advanced Drug Delivery Group, School of Pharmacy, University of Sydney, Sydney, NSW, Australia (2). Centenary Institute and Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia (3). Institute for Bioscience and Biotechnology Research, University of Maryland, Rockville, Maryland, USA
Endolysin Cpl-1 is known to have antimicrobial activity against Streptococcus pneumoniae, which causes lung infection. Administration of Cpl-1 as an inhalation aerosol to the lungs will target the infection directly, potentially minimizing the dose required and adverse effects, while optimizing the efficacy. We have previously shown that Cpl-1 remained stable when aerosolized by vibrating mesh nebulization, which confirmed the feasibility to nebulize endolysins for inhalation delivery. We have recently further investigated the efficacy of inhaled Cp1-1 powder and liquid formulations to treat S. pneumoniae in a murine lung infection model. Single treatment of Cpl-1 liquid or powder (40 μg per animal, n=4) decreased the pulmonary bacterial load by approximately 1-log. In contrast, a combination liquid formulation containing Cpl-1 and another endolysin Pal (20 μg each per animal) induced a 2-log reduction of pulmonary bacteria counts in mice. The results provide proof-of-concept that inhalable endolysin formulations can treat bacterial lung infections, and that combining endolysins may enhance antimicrobial activity compared to monotherapy.