Mucosomes as next-generation drug carriers for treating mucus-resident bacterial infections and biofilms

Abstract

Deaths connected to bacterial infections are expected to outnumber those caused by cancer by 2050. Multiple advantages, including enhanced efficacy of the treatment, characterize the use of nanocarriers to deliver antibiotics. This work explores the use of mucosomes – intrinsically glycosylated mucin nanoparticles – to deliver ciprofloxacin to fight Pseudomonas aeruginosa and Staphylococcus aureus infections. Mucins are a family of glycoproteins representing the major non-aqueous component of human mucus and are known for actively interacting with bacteria, reducing their virulence, and limiting their aggregations. This study shows that these critical properties of mucin are preserved in mucosomes, enabling a strong synergy with the loaded antimicrobial drug. Empty mucosomes exert a bacteriostatic activity, inhibiting bacterial growth up to 70%. Ciprofloxacin-loaded mucosomes were able to decrease the minimum inhibitory concentration of ciprofloxacin against S. aureus by up to 50%. Mucosomes could prevent biofilm formation and disassemble well-established biofilms by reducing the biomass by up to 98%. Mucosomes further facilitated the transmucosal delivery of ciprofloxacin in a 3D mucus-mimicking model. These results, together with the possibility of freeze-drying and storing drug-loaded mucosomes without impairing their efficacy, suggest the suitability of this approach to tackle mucosal bacterial infections. Interestingly, this nanosystem has been shown to enhance the phagocytic action of blood in eradicating bacterial biofilms.