Hybrid Nanoparticles of Poly (Methyl Methacrylate) and Antimicrobial Quaternary Ammonium Surfactants

Abstract

Quaternary ammonium surfactants (QACs) are microbicides, whereas poly (acrylates) are biocompatible polymers. Here, the physical and antimicrobial properties of two QACs, cetyl trimethyl ammonium bromide (CTAB) or dioctadecyl dimethyl ammonium bromide (DODAB) in poly (methyl methacrylate) (PMMA) nanoparticles (NPs) are compared to those of QACs alone. Methyl methacrylate (MMA) polymerization using DODAB or CTAB as emulsifiers and initiator azobisisobutyronitrile (AIBN) yielded cationic, nanometric, homodisperse, and stable NPs. NPs’ physical and antimicrobial properties were assessed from dynamic light scattering (DLS), scanning electron microscopy, and viability curves of Escherichia coli, Staphylococcus aureus, or Candida albicans determined as log(colony-forming unities counting) over a range of [QACs]. NPs were spherical and homodisperse but activity for free QACs was higher than those for QACs in NPs. Inhibition halos against bacteria and yeast were observed only for free or incorporated CTAB in NPs because PMMA/CTAB NPs controlled the CTAB release. DODAB displayed fungicidal activity against C. albicans since DODAB bilayer disks could penetrate the outer glycoproteins fungus layer. The physical properties and stability of the cationic NPs highlighted their potential to combine with other bioactive molecules for further applications in drug and vaccine delivery.

Biocompatible Lipid Polymer Cationic Nanoparticles for Antigen Presentation

“…The search for cationic NPs with potential as adjuvants for vaccines yielded many examples of polymer lipid [ 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 ], silica/cationic lipid [ 18 , 19 ], cationic polymer [ 20 , 21 , 22 ], gold/cationic polymer NPs [ 23 ], and iron-oxide/cationic polymer/antigen NPs [ 24 ]. Among the most important requirements of adjuvants for vaccines are biocompatibility and nanometric size [ 25 ].…”

“…Two different modes of interaction between lipids and polymers were previously disclosed: (1) Lipids phase-separating from polymers (low miscibility lipid/polymer); in this case, bilayer adsorption sometimes took place on the surface of polymer NPs [ 10 , 28 , 29 , 30 ]. (2) Lipids mixing well with the polymer such as DODAB and PMMA [ 9 , 11 , 13 , 15 , 31 ].…”

Cationic Nanostructures for Vaccines Design

“…In another instance, DODAB cationic bilayer surrounded polystyrene sulfate particles available over a range of diameters [ 205 , 206 , 207 ] or silica particles [ 208 , 209 ]; recently optimal coverage with single cationic bilayers on the anionic polymeric or inorganic particles was achieved [ 207 , 209 ]. Synthetic biocompatible polymers such as PMMA were also hybridized with cationic polymers or cationic lipids or surfactants [ 160 , 161 , 162 , 163 , 210 , 211 , 212 , 213 ]. In summary, a variety of model hybrid and cationic delivery systems are already available to combine with a myriad of oppositely charged antigens for vaccine design [ 25 , 163 , 214 , 215 ].…”

“…Non-covalent nanoparticle (NP) assemblies of PMMA, a synthetic, non-charged, and biocompatible polymer, and PDDA polycation have been described earlier by our group since the first report on the good compatibility and miscibility of PDDA with PMMA evaluated from microbicidal PMMA/PDDA NPs [ 160 , 161 , 162 , 163 , 210 , 211 , 212 , 213 , 214 ]. The synthesis of PMMA NPs by emulsion polymerization of MMA in the presence of PDDA yielded cationic, homodisperse, and stable NPs [ 160 , 212 ], which are presently being evaluated in our group for possible applications as immunoadjuvants.…”

“…Diverse types of arrangement between lipids and polymers have been described; in general, these hybrid assemblies could be classified as lipid–polymer or polymer–lipid, depending on the position of each material in the hybrid structure; either the polymer or the lipid is in the inner part the nanostructure. In addition, polymer and lipid may mix, driven by intermolecular interactions, so that the lipid may become embedded in the polymer matrix displaying good compatibility with the polymer [ 210 , 212 , 213 , 253 , 254 ].…”