Phosphoryicholine-Based Polymer Encapsulated Chitosan Nanoparticles Enhance the Penetration of Antimicrobials in a Staphylococcal Biofilm

Cao, JJ (Cao, Jingjing)^{[ 1,2 ]} ; Zhao, Y (Zhao, Yu)^{[ 1,2 ]} ; Liu, Y (Liu, Yong)^{[ 1,2,3,4 ]} ; Tian, S (Tian, Shuang)^{[ 1,2 ]} ; Zheng, CX (Zheng, Chunxiong)^{[ 1,2 ]} ; Liu, CH (Liu, Chenhui)^{[ 1,2 ]} ; Zhai, Y (Zhai, Yan)^{[ 1,2 ]} ; An, YL (An, Yingli)^{[ 1,2 ]} ; Busscher, HJ (Busscher, Henk J.)^{[ 1,2,3,4 ]} ; Shi, LQ (Shi, Linqi)^{[ 1,2 ]} ; Liu, Y (Liu, Yang)^{[ 1,2 ]}

ACS MACRO LETTERS, 2019, 8(6): 651-657

DOI: 10.1021/acsmacrolett.9b00142

摘要

Biofilms that contribute to the persistent bacterial infections pose serious threats to human health, due in part to the extracellular polymeric substances (EPS) matrix of biofilm block the diffusion of intact antimicrobials. The poor penetration of antimicrobials into biofilm greatly reduces their bacterial killing efficacy. Here, we have demonstrated a nanocapsule PMPC-CS synthesized by encapsulating a chitosan nanoparticle with poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC). Such PMPC-based surface exhibited low EPS-adsorption, allowing enhanced penetration of PMPC-CS. Additionally, PMPC-CS showed effective targeting toward negatively charged bacterial cell surfaces and pH-responsive drug release mediated by the swelling of chitosan core under the acidic environment of biofilm. These unique features ensured targeted delivery of antimicrobials throughout the depth of a biofilm. Delivery of triclosan with PMPC-CS outperformed direct application of free triclosan in inhibiting the growth of bacteria in biofilm, suggesting the potential of PMPC-CS as an effective delivery system for the treatment of bacterial infections.