Antimicrobial and Anti‐Biofilm Activities of Surface Engineered Polycationic Albumin Nanoparticles with Reduced Hemolytic Activity

Abstract

Protein-based polymeric polyelectrolytes are emerging as alternative synthetic nanoparticles owing to their biodegradability and biocompatibility. However, potential in vivo toxicity remains a significant challenge. Herein an array of protein polyelectrolytes generated from cationic human serum albumin (cHSA) and polyethylene glycol (PEG) are synthesized via synthetic customization as antimicrobials for the treatment of systemic infections. By varying PEG molecular weight and chain length, in vitro hemolytic activity can be fine-tuned without significantly affecting antimicrobial potency. The optimal hybrid material, PEG (2000) -cHSA, with potent antimicrobial character, low hemolytic activity, and in vitro biofilm disruptive properties is identified. Surface plasmon resonance (SPR) evaluation demonstrates significantly higher binding activity of the protein nanoparticles to bacteria cell wall components and microfluidic live-cell imaging indicates that the nanoparticles act through a membranolytic mechanism. Given their low susceptibility to drug resistance and potent activity against resistant bacteria strains, these findings establish the PEGylated albumin nanoparticles as a potent weaponry against drug resistance and biofilm-related infection.

Enhanced Antimicrobial and Antibiofilm Effect of New Colistin-Loaded Human Albumin Nanoparticles

“…The complexation of proteins and polysaccharides via non covalent interactions, such as hydrophobic and electrostatic ones, has been previously evaluated for the formulation of nanoparticles [ 33 , 34 ]. Even if recently antibacterial properties of albumin have been also hypothesized [ 35 , 36 , 37 ], albumin nanoparticles for antibiotic delivery have not been deeply investigated and to date no such formulations loaded with Colistin have been developed.…”

“…Compared to results obtained by Pastor M et al [ 46 ] using sodium Colistin methate-loaded lipid nanocarries and by Sans-Serramitjiana E et al [ 23 ] using nanoencapsulated Colistin sulfate that demonstrated an identical activity of free and loaded Colistin against biofilm prevention of P. aeruginosa , we noticed a great effect of our albumin nanoparticles to prevent biofilm formation of A. baumannii . Recently, an effect of PEG-cHSA (cationic human serum albumin) was observed only using MIC and supra-MIC concentrations to prevent P. aeruginosa biofilms [ 35 ]. The biofilm-modulating action of MIC and sub-MICs depends on many factors: type of antimicrobial, mode of action, bacterial strain and susceptibility or resistance of the strain.…”

Albumin-Based LL37 Peptide Nanoparticles as a Sustained Release System against Pseudomonas aeruginosa Lung Infection

“…Albumin nanoparticles have recently emerged as alternative carrier for various types of diseases. Sybil et al established an array of protein polyelectrolytes generated from cationic human serum albumin (c-HSA) and polyethylene glycol (PEG), which were synthesized via synthetic customization as antimicrobials for the treatment of systemic infections. Woods et al demonstrated that albumin particles were well tolerated in the mouse lung and exhibits a long residence time after deposition (>48 h) .…”

Nucleic Acid Hybrids as Advanced Antibacterial Nanocarriers

“…On the other hand, metallic nanoparticles are limited by toxicity concerns (e.g., naked iron oxide nanoparticles) and aggregation issues (e.g., silver nanoparticles) [28,29]. Similarly, the chemical composition of polymeric nanoparticles, physicochemical properties (e.g., surface potential) and/or their subsequent degradation products have also been associated with cell toxicity, stress and inflammatory responses [30][31][32]. Recent strategies to uncover advanced delivery systems with improved physicochemical properties and antibacterial effects include the development of nucleic acid nanocarriers and their conjugates.…”