Dual Corona Vesicles with Intrinsic Antibacterial and Enhanced Antibiotic Delivery Capabilities for Effective Treatment of Biofilm-Induced Periodontitis.

Abstract

Periodontitis is a common disease caused by plaque biofilms, which are important pathogenic factors of many diseases and may be eradicated by antibiotic therapy. However, low-dose antibiotic therapy is a complicated challenge for eradicating biofilms as hundreds (even thousands) of times higher concentrations of antibiotics are needed than killing planktonic bacteria. Polymer vesicles may solve these problems via effective antibiotic delivery into biofilms, but traditional single corona vesicles lack the multifunctionalities essential for biofilm eradication. In this paper, we aim to effectively treat biofilm-induced periodontitis using much lower concentrations of antibiotics than traditional antibiotic therapy by designing a multifunctional dual corona vesicle with intrinsic antibacterial and enhanced antibiotic delivery capabilities. This vesicle is co-assembled from two block copolymers, poly(ε-caprolactone)-block-poly(lysine-stat-phenylalanine) [PCL-b-P(Lys-stat-Phe)] and poly(ethylene oxide)-block-poly(ε-caprolactone) [PEO-b-PCL]. Both PEO and P(Lys-stat-Phe) coronas have their specific functions: PEO endows vesicles with protein repelling ability to penetrate extracellular polymeric substances in biofilms ("stealthy" coronas), whereas P(Lys-stat-Phe) provides vesicles with positive charges and broad spectrum intrinsic antibacterial activity. As a result, the dosage of antibiotics can be reduced by 50% when encapsulated in the dual corona vesicles to eradicate Escherichia coli or Staphylococcus aureus biofilms. Furthermore, effective in vivo treatment has been achieved from a rat periodontitis model, as confirmed by significantly reduced dental plaque, and alleviated inflammation. Overall, this "stealthy" and antibacterial dual corona vesicle demonstrates a fresh insight for improving the antibiofilm efficiency of antibiotics and combating the serious threat of biofilm-associated diseases.