Now showing 1 - 5 of 5
  • Publication
    Evaluation of Selenomethionine Entrapped in Nanoparticles for Oral Supplementation Using In Vitro, Ex Vivo and In Vivo Models
    Selenium methionine (SeMet) is an essential micronutrient required for normal body function and is associated with additional health benefits. However, oral administration of SeMet can be challenging due to its purported narrow therapeutic index, low oral bioavailability, and high susceptibility to oxidation. To address these issues, SeMet was entrapped in zein-coated nanoparticles made from chitosan using an ionic gelation formulation. The high stability of both the SeMet and selenomethionine nanoparticles (SeMet-NPs) was established using cultured human intestinal and liver epithelial cells, rat liver homogenates, and rat intestinal homogenates and lumen washes. Minimal cytotoxicity to Caco-2 and HepG2 cells was observed for SeMet and SeMet-NPs. Antioxidant properties of SeMet were revealed using a Reactive Oxygen Species (ROS) assay, based on the observation of a concentration-dependent reduction in the build-up of peroxides, hydroxides and hydroxyl radicals in Caco-2 cells exposed to SeMet (6.25–100 μM). The basal apparent permeability coefficient (Papp) of SeMet across isolated rat jejunal mucosae mounted in Ussing chambers was low, but the Papp was increased when presented in NP. SeMet had minimal effects on the electrogenic ion secretion of rat jejunal and colonic mucosae in Ussing chambers. Intra-jejunal injections of SeMet-NPs to rats yielded increased plasma levels of SeMet after 3 h for the SeMet-NPs compared to free SeMet. Overall, there is potential to further develop SeMet-NPs for oral supplementation due to the increased intestinal permeability, versus free SeMet, and the low potential for toxicity.
      49
  • Publication
    Application of Box-Behnken experimental design for the formulation and optimisation of selenomethionine-loaded chitosan nanoparticles coated with zein for oral delivery
    Selenomethionine is an essential amino acid with a narrow therapeutic index and susceptibility to oxidation. Here it was encapsulated into a nanoparticle composed of chitosan cross-linked with tripolyphosphate for oral delivery. The formulation was optimised using a three-factor Box-Behnken experimental design. The chitosan:tripolyphosphate ratio, chitosan solvent pH, and drug load concentration were independently varied. The dependent variables studied were encapsulation efficiency, particle size, polydispersity index and zeta potential. For optimisation, encapsulation efficiency and zeta potential were maximised, particle diameter was set to 300 nm and polydispersity index was minimised. A 0.15 mg/mL concentration of selenomethionine, chitosan solvent pH of 3, and chitosan:tripolyphosphate ratio of 6:1 yielded optimum nanoparticles of size 187 ± 58 nm, polydispersity index 0.24 ± 0.01, zeta potential 36 ± 6 mV, and encapsulation efficiency of 39 ± 3%. Encapsulation efficiency was doubled to 80 ± 1.5% by varying pH of the ionotropic solution components and by subsequent coating of the NPs with zein, increasing NP diameter to 377 ± 47 nm, whilst retaining polydispersity index and zeta potential values. Selenomethionine-entrapped nanoparticles were not cytotoxic to intestinal and liver cell lines. Accelerated thermal stability studies indicated good stability of the nanoparticles under normal storage conditions (23 °C). In simulated gastrointestinal and intestinal fluid conditions, 60% cumulative release was obtained over 6 h.
    Scopus© Citations 26  432
  • Publication
    Formulation, Characterization and Stability Assessment of a Food‐Derived Tripeptide, Leucine‐Lysine‐Proline Loaded Chitosan Nanoparticles
    The chicken‐ or fish‐derived tripeptide, leucine‐lysine‐proline (LKP), inhibits the angiotensin converting enzyme and may be used as an alternative treatment for prehypertension. However, it has low permeation across the small intestine. The formulation of LKP into a nanoparticle (NP) has the potential to address this issue. LKP‐loaded NPs were produced using an ionotropic gelation technique, using chitosan (CL113). Following optimization of unloaded NPs, a mixture amount design was constructed using variable concentration of CL113 and tripolyphosphate at a fixed LKP concentration. Resultant particle sizes ranged from 120 to 271 nm, zeta potential values from 29 to 37 mV, and polydispersity values from 0.3 to 0.6. A ratio of 6:1 (CL113:TPP) produced the best encapsulation of approximately 65%. Accelerated studies of the loaded NPs indicated stability under normal storage conditions (room temperature). Cytotoxicity assessment showed no significant loss of cell viability and in vitro release studies indicated an initial burst followed by a slower and sustained release.
    Scopus© Citations 8  331
  • Publication
    Nutraceutical formulation, characterisation, and in-vitro evaluation of methylselenocysteine and selenocystine using food derived chitosan: zein nanoparticles
    Selenoamino acids (SeAAs) have been shown to possess antioxidant and anticancer properties. However, their bioaccessibility is low and they may be toxic above the recommended nutritional intake level, thus improved targeted oral delivery methods are desirable. In this work, the SeAAs, Methylselenocysteine (MSC) and selenocystine (SeCys2) were encapsulated into nanoparticles (NPs) using the mucoadhesive polymer chitosan (Cs), via ionotropic gelation with tripolyphosphate (TPP) and the NPs produced were then coated with zein (a maize derived prolamine rich protein). NPs with optimized physicochemical properties for oral delivery were obtained at a 6: 1 ratio of Cs:TPP, with a 1:0.75 mass ratio of Cs:zein coating (diameter ~260 nm, polydispersivity index ~0.2, zeta potential >30 mV). Scanning Electron Microscopy (SEM) analysis showed that spheroidal, well distributed particles were obtained. Encapsulation Efficiencies of 80.7% and 78.9% were achieved, respectively, for MSC and SeCys2 loaded NPs. Cytotoxicity studies of MSC loaded NPs showed no decrease in cellular viability in either Caco-2 (intestine) or HepG2 (liver) cells after 4 and 72 h exposures. For SeCys2 loaded NPs, although no cytotoxicity was observed in Caco-2 cells after 4 h, a significant reduction in cytotoxicity was observed, compared to pure SeCys2, across all test concentrations in HepG2 after 72 h exposure. Accelerated thermal stability testing of both loaded NPs indicated good stability under normal storage conditions. Lastly, after 6 h exposure to simulated gastrointestinal tract environments, the sustained release profile of the formulation showed that 62 ± 8% and 69 ± 4% of MSC and SeCys2, had been released from the NPs respectively.
      748Scopus© Citations 21
  • Publication
    Comparative study of the structural and physicochemical properties of two food derived antihypertensive tri-peptides, Isoleucine-Proline-Proline and Leucine-Lysine-Proline encapsulated into a chitosan based nanoparticle system
    Food derived tri-peptides; Leucine-Lysine-Proline (LKP) and Isoleucine-Proline-Proline (IPP) are angiotensin converting enzyme inhibitors and may have potential to alleviate hypertension. The aim of this work was to understand the interactions of IPP and LKP when formulated into a chitosan nanoparticle (NP) to help improve permeation. Our findings indicate different mean inhibitory concentrations (LKP: 0.36 ± 0.01 μM and IPP: 3.1 ± 0.6 μM) and encapsulation efficiencies at different ratios of chitosan: tripolyphosphate (LKP NPs: 65% at 6:1 and IPP NPs: 43% at 4:1). Molecular modelling and circular dichroism showed different stable amino side-chain-specific conformations for each peptide. IPP showed more steric hindrances to intra-chain rotations, resulting in an unordered peptide structure, whereas LKP showed more flexibility associated with a (disordered) β-strand-like conformer. In-vitro release kinetics showed a slower release for LKP NPs in acidic pH compared to IPP NPs. In conclusion, LKP NPs were found to have better binding compatibility with chitosan.
      538Scopus© Citations 14