Abdulkarim, M. (Muthanna)
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- Modulation of the fate of zein nanoparticles by their coating with a Gantrez® AN-thiamine polymer conjugate(2019) Inchaurraga-Casadamon, L. (Laura); Peñuelas-Sanchez, I. (Ivan); Martin-Arbella, N. (Nekane); Quincoces, G. (Gemma); Abdulkarim, M. (Muthanna); Gumbleton, M. (Mark); López, A. (Andrés); Irache, J.M. (Juan Manuel)The aim of this work was to evaluate the mucus-permeating properties of nanocarriers using zein nanoparticles (NPZ) coated with a Gantrez® AN-thiamine conjugate (GT). NPZ were coated by incubation at different GT-tozein ratios: 2.5% coating with GT (GT-NPZ1), 5% (GT-NPZ2) and 10% (GT-NPZ3). During the process, the GT conjugate formed a polymer layer around the surface of zein nanoparticles. For GT-NPZ2, the thickness of this corona was estimated between 15 and 20 nm. These nanocarriers displayed a more negative zeta potential than uncoated NPZ. The diffusivity of nanoparticles was evaluated in pig intestinal mucus by multiple particle tracking analysis. GT-NPZ2 displayed a 28-fold higher diffusion coefficient within the mucus layer than NPZ particles. These results align with in vivo biodistribution studies in which NPZ displayed a localisation restricted to the mucus layer, whereas GT-NPZ2 were capable of reaching the intestinal epithelium. The gastro-intestinal transit of mucoadhesive (NPZ) and mucus-permeating nanoparticles (GT-NPZ2) was also found to be different. Thus, mucoadhesive nanoparticles displayed a significant accumulation in the stomach of animals, whereas mucus-penetrating nanoparticles appeared to exit the stomach more rapidly to access the small intestine of animals
- Oral immunogenicity in mice and sows of enterotoxigenic escherichia coli outer-membrane vesicles incorporated into zein-based nanoparticles(MDPI AG, 2020) Brotons-Canto, A. (Ana); Cenoz, S. (Santiago); Abdulkarim, M. (Muthanna); Pérez, I. (Isidoro); Gumbleton, M. (Mark); Gamazo, C. (Carlos); Matías, J. (Jose); Irache, J.M. (Juan Manuel)Enterotoxigenic Escherichia coli (ETEC) strains are a major cause of illness and death in neonatal and recently weaned pigs. The immune protection of the piglets derives from maternal colostrum, since this species does not receive maternal antibodies through the placenta. In the present study, outer membrane vesicles (OMVs) obtained from main ETEC strains involved in piglet infection (F4 and F18 serotypes), encapsulated into zein nanoparticles coated with Gantrez®® AN-mannosamine conjugate, were used to orally immunize mice and pregnant sows. Loaded nanoparticles were homogeneous and spherical in a shape, with a size of 220–280 nm. The diffusion of nanoparticles through porcine intestinal mucus barrier was assessed by a Multiple Particle Tracking technique, showing that these particles were able to diffuse efficiently (1.3% diffusion coefficient), validating their oral use. BALB/c mice were either orally immunized with free OMVs or encapsulated into nanoparticles (100 µg OMVs/mouse). Results indicated that a single dose of loaded nanoparticles was able to elicit higher levels of serum specific IgG1, IgG2a and IgA, as well as intestinal IgA, with respect to the free antigens. In addition, nanoparticles induced an increase in levels of IL-2, IL-4 and IFN-γ with respect to the administration of free OMVs. Orally immunized pregnant sows with the same formulation elicited colostrum-, serum- (IgG, IgA or IgM) and fecal- (IgA) specific antibodies and, what is most relevant, offspring suckling piglets presented specific IgG in serum. Further studies are needed to determine the infection protective capacity of this new oral subunit vaccine