Now showing 1 - 4 of 4
  • 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  427
  • 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.
      530Scopus© Citations 14
  • 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  329
  • Publication
    Formulation, Characterisation and Evaluation of the Antihypertensive Peptides, Isoleucine-Proline-Proline and Leucine-Lysine-Proline in Chitosan Nanoparticles Coated with Zein for Oral Drug Delivery
    Isoleucine-Proline-Proline (IPP) and Leucine-Lysine-Proline (LKP) are food-derived tripeptides whose antihypertensive functions have been demonstrated in hypertensive rat models. However, peptides display low oral bioavailability due to poor intestinal epithelial permeability and instability. IPP and LKP were formulated into nanoparticles (NP) using chitosan (CL113) via ionotropic gelation and then coated with zein. Following addition of zein, a high encapsulation efficiency (EE) (>80%) was obtained for the NP. In simulated gastric fluid (SGF), 20% cumulative release of the peptides was achieved after 2 h, whereas in simulated intestinal fluid (SIF), ~90% cumulative release was observed after 6 h. Higher colloidal stability (39–41 mV) was observed for the coated NP compared to uncoated ones (30–35 mV). In vitro cytotoxicity studies showed no reduction in cellular viability of human intestinal epithelial Caco-2 and HepG2 liver cells upon exposure to NP and NP components. Administration of NP encapsulating IPP and LKP by oral gavage to spontaneously hypertensive rats (SHR) attenuated systolic blood pressure (SBP) for 8 h. This suggests that the NP provide appropriate release to achieve prolonged hypotensive effects in vivo. In conclusion, chitosan-zein nanoparticles (CZ NP) have potential as oral delivery system for the encapsulation of IPP and LKP.
      36Scopus© Citations 9