Polymyxin B sulfate inhalable microparticles with high-lectin-affinity sugar carriers for efficient treatment of biofilm-associated pulmonary infections
Yue Zhou, Jiayuan Huang, Guanlin Wang, Zizhao Zhai, Maizbha Uddin Ahmed, Xiao Xia, Cenfeng Liu, Yuzhen Jin, Xin Pan, Ying Huang, Chuanbin Wu, Xuejuan Zhang
Abstract
Pulmonary infections caused by multidrug-resistant bacteria have become a significant threat to human health. Bacterial biofilms exacerbate the persistence and recurrence of pulmonary infections, hindering the accessibility and effectiveness of antibiotics. In this study, a dry powder inhalation (DPI) consisting of polymyxin B sulfate (PMBS) inhalable microparticles and high-lectin-affinity (HLA) sugar (i.e., raffinose) carriers was developed for treating pulmonary infections and targeting bacterial lectins essential for biofilm growth. The formulated PMBS-HLA DPIs exhibited particle sizes of approximately 3 μm, and surface roughness varied according to the drug-to-carrier ratio. Formulation F5 (PMBS: raffinose = 10: 90) demonstrated the highest fine particle fraction (FPF) value (64.86%), signifying its substantially enhanced aerosol performance, potentially attributable to moderate roughness and smallest mass median aerodynamic particle size. The efficacy of PMBS-HLA DPIs in inhibiting biofilm formation and eradicating mature biofilms was significantly improved with the addition of raffinose, suggesting the effectiveness of lectin-binding strategy for combating bacterial biofilm-associated infections. In rat models with acute and chronic pulmonary infections, F5 demonstrated superior bacterial killing and amelioration of inflammatory responses compared to spray-dried PMBS (F0). In conclusion, our HLA carrier-based formulation presents considerable potential for the efficient treatment of multidrug-resistant bacterial biofilm-associated pulmonary infections.