Targeting Pulmonary Bacterial And Fungal Infections With Inhalable Cannabinoids And Pentamidine

Abstract

Pulmonary infections caused by drug-resistant bacteria and opportunistic pathogens remain a serious threat to immunocompromised and hospitalised patients. The rise of antibiotic resistance and the burden of infections such as Methicillin-resistant Staphylococcus aureus (MRSA) pneumonia and Pneumocystis jirovecii pneumonia (PJP) highlight the need for new therapeutic approaches. Drug repurposing offers a strategy to accelerate translation of existing medicines into novel delivery systems with known safety. Cannabinoids, particularly cannabidiol (CBD), have long been known for its neurological and anti-inflammatory properties. They have also demonstrated promising antibacterial action against Gram-positive infections such as MRSA. When combined with vancomycin, a first-line MRSA antibiotic, they have the potential to enhance bactericidal action and prolong antimicrobial activity. Yet, systemic delivery limits the effectiveness of both agents in respiratory infections. Similarly, while pentamidine is beneficial in PJP prophylaxis, it is not a commonly used therapeutic option due to the risks and clinical burden of nebulised therapy. Inhalable delivery, especially by dry powder inhaler enables targeted lung deposition at high concentrations while minimising systemic exposure, environmental contamination, and administration burden. Reformulating repurposed drugs into inhalable powders represents a practical strategy to improve treatment of respiratory infections. This thesis explores the antibacterial effects of cannabinoids on MRSA biofilms and the development of inhalable CBD–vancomycin and pentamidine powders as targeted therapies for MRSA lung infections and PJP, respectively. By integrating antimicrobial innovation with advanced pulmonary delivery technology, this work aims to address critical gaps in current treatment options for life-threatening lung infections.