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.

Emerging Trends in Nanomaterials for Antibacterial Applications

“…This adhesion occurs through electrostatic bonds between the positive charges of polymeric antimicrobials and negative charges of bacterial cell walls. 203 , 204 However, the drawback of cationic NPs is their interactions with protein corona once in the peripheral blood. 205 , 206 To overcome this disadvantage, Congyu Wang and co-workers used a strategy based on charge reversal to design caged guanidine NPs (CGNs).…”

Polymer Vesicles for Antimicrobial Applications

“…Importantly, this formulation was selectively toxic towards methicillin-resistant biofilm cells rather than mammalian cells, demonstrating the high selectivity of the multi-compartment vesicles. Recently, Du and coworkers [102] prepared dual corona polymer vesicles by the coassembly of PEO-b-PCL and PCL-b-P(Lys-stat-Phe), which could efficiently deliver antibiotics to biofilms and treat biofilm-induced periodontitis at a much lower concentration Recently, Du and coworkers [102] prepared dual corona polymer vesicles by the co-assembly of PEO-b-PCL and PCL-b-P(Lys-stat-Phe), which could efficiently deliver antibiotics to biofilms and treat biofilm-induced periodontitis at a much lower concentration of antibiotics due to the synergy of the intrinsic antimicrobial activity of the polymer vesicles and antibiotics. The dual corona was formed by PEO and P(Lys-stat-Phe) chains, and the former provided protein-repelling capability to penetrate the EPS, while the latter endowed the vesicles with positively charged surface and broad-spectrum antimicrobial activity.…”

Approaches for the inhibition and elimination of microbial biofilms using macromolecular agents

“…6A. 183 These showed intrinsic broad-spectrum antimicrobial activity imparted by the polypeptide P(Lys-stat-Phe) corona and stealth-like protein repellence imparted by the PEO corona, as well as biodegradability imparted by the hydrolytic properties of the PCL core. The latter property allowed these nanoparticles to penetrate deeper into S. aureus and E. coli biofilms.…”

“…Topical treatment with the antibiotic-loaded vesicles was shown to significantly reduce bacterial plaque formation, gingival bleeding and periodontal inflammation in a rat periodontitis model, whilst requiring just 50% of the loaded antibiotic to achieve similar bactericidal effects. 183 Similarly, van der Mei and Shi et al developed surface adaptive mixed corona micelles comprised of a PCL core and a mixed corona of both PEO and a pH-responsive poly(b-amino ester). 185 PEO provided stealth properties until acidification in the S. aureus biofilm environment, which led to cationization of the poly(b-amino ester) block.…”