Biocompatible Lipid Polymer Cationic Nanoparticles for Antigen Presentation

Abstract

Biocompatible lipid polymer nanoparticles (NPs) previously used as antimicrobial agents are explored here as immuno-adjuvants. Poly (methyl methacrylate) (PMMA)/dioctadecyldimethylammonium bromide (DODAB)/poly (diallyldimethylammonium chloride) (PDDA) nanoparticles (NPs) were prepared by emulsion polymerization of methyl methacrylate (MMA) in the presence of DODAB and PDDA, with azobisisobutyronitrile (AIBN) as the initiator. NPs characterization after dialysis by dynamic light-scattering yielded 225 ± 2 nm hydrodynamic diameter (Dz), 73 ± 1 mV zeta-potential (ζ), and 0.10 ± 0.01 polydispersity (P). Ovalbumin (OVA) adsorption reduced ζ to 45 ± 2 mV. Balb/c mice immunized with NPs/OVA produced enhanced OVA-specific IgG1 and IgG2a, exhibited moderate delayed type hypersensitivity reaction, and enhanced cytokines production (IL-4, IL-10, IL-2, IFN-γ) by cultured spleen cells. There was no cytotoxicity against cultured macrophages and fibroblasts. Advantages of the PMMA/DODAB/PDDA NPs were high biocompatibility, zeta-potential, colloidal stability, and antigen adsorption. Both humoral and cellular antigen-specific immune responses were obtained.

Antimicrobial Polymer−Based Assemblies: A Review

“…Certain APs showed dose−dependent cytotoxicity against human epithelial cells, lung fibroblasts, and monocytes [ 128 ]. Nevertheless, their high antimicrobial activity at low doses has been the main motivation for the intense and extensive research on APs over the last twenty years [ 10 , 13 , 14 , 15 , 17 , 129 ]; they have been often described as a promising platform for the development of next−generation antimicrobial agents [ 120 , 122 ]. In addition, their flexible properties, facile synthesis, or modification from natural polymers, such as chitosan, gelatin, dextran, starch, or cellulose, also led to various alternative therapeutic applications [ 20 , 130 ].…”

“…In addition, their flexible properties, facile synthesis, or modification from natural polymers, such as chitosan, gelatin, dextran, starch, or cellulose, also led to various alternative therapeutic applications [ 20 , 130 ]. Among their important applications, APs have been used as adjuvants for vaccine design and antigen presentation [ 126 , 127 , 129 ] and for gene and drug delivery [ 131 ]; interestingly, aminated microcrystalline cellulose killed melanoma and breast cancer cell lines in culture [ 131 ]. Excellent overviews on the synthesis and preparation of cationic polymers are available [ 48 , 130 , 132 , 133 ].…”

Cationic and Biocompatible Polymer/Lipid Nanoparticles as Immunoadjuvants

“…Centrifuging dispersions (1 h/10,000 rpm) and pelleting NPs allowed the determination of DODAB concentration in the supernatant from halide microtitration [46]. DODAB concentration in NPs was obtained by subtracting DODAB concentration in the supernatant from DODAB concentration used for NPs synthesis [21,45].…”

“…Two weeks after the booster, spleen cells from spleens of five immunized mice of the same group were cultured in RPMI 1640 medium with 2 mM L-glutamine, 5% FBS and 0.25% 2-mercaptoethanol [21,49]. Suspensions (8 × 10 6 cells/mL) distributed in tissue culture plates were incubated with medium containing 250 µg/mL OVA in a humidified CO 2 incubator for 72 h. Negative and positive controls were medium only or 2.5 µg/mL concanavalin A (Con-A), respectively.…”

“…Their nanometric size avoids retention by physiological barriers at the site of injection allowing them to reach lymph nodes and dendritic cells more easily [1][2][3][4][5][6]. They can be obtained from a variety of lipids, polymers or lipids and polymers, mostly as bilayer vesicles [7,8], open bilayer disks [9][10][11][12][13], lipid nanoparticles [14] or hybrid nanoparticles [15][16][17][18][19][20][21].…”