A novel approach to oral iron delivery using ferrous sulphate loaded solid lipid nanoparticles

Gulrez Zariwala, M., Elsaid, N., Jackson, T.L., Corral López, F., Farnaud, S., Somavarapu, S. and Renshaw, D. 2013. A novel approach to oral iron delivery using ferrous sulphate loaded solid lipid nanoparticles. International Journal of Pharmaceutics. 456 (2), pp. 400-407. https://doi.org/10.1016/j.ijpharm.2013.08.070

TitleA novel approach to oral iron delivery using ferrous sulphate loaded solid lipid nanoparticles
AuthorsGulrez Zariwala, M., Elsaid, N., Jackson, T.L., Corral López, F., Farnaud, S., Somavarapu, S. and Renshaw, D.
Abstract

Iron (Fe) loaded solid lipid nanoparticles (SLN’s) were formulated using stearic acid and iron absorp-tion was evaluated in vitro using the cell line Caco-2 with intracellular ferritin formation as a marker ofiron absorption. Iron loading was optimised at 1% Fe (w/w) lipid since an inverse relation was observedbetween initial iron concentration and SLN iron incorporation efficiency. Chitosan (Chi) was included toprepare chitosan coated SLN’s. Particle size analysis revealed a sub-micron size range (300.3 ± 31.75 nmto 495.1 ± 80.42 nm), with chitosan containing particles having the largest dimensions. As expected,chitosan (0.1%, 0.2% and 0.4% w/v) conferred a net positive charge on the particle surface in a concen-tration dependent manner. For iron absorption experiments equal doses of Fe (20 �M) from selectedformulations (SLN-FeA and SLN-Fe-ChiB) were added to Caco-2 cells and intracellular ferritin proteinconcentrations determined. Caco-2 iron absorption from SLN-FeA (583.98 ± 40.83 ng/mg cell protein)and chitosan containing SLN-Fe-ChiB (642.77 ± 29.37 ng/mg cell protein) were 13.42% and 24.9% greaterthan that from ferrous sulphate (FeSO4) reference (514.66 ± 20.43 ng/mg cell protein) (p ≤ 0.05). Wedemonstrate for the first time preparation, characterisation and superior iron absorption in vitro fromSLN’s, suggesting the potential of these formulations as a novel system for oral iron delivery.

JournalInternational Journal of Pharmaceutics
Journal citation456 (2), pp. 400-407
ISSN0378-5173
YearNov 2013
PublisherElsevier
Digital Object Identifier (DOI)https://doi.org/10.1016/j.ijpharm.2013.08.070
Publication dates
PublishedNov 2013
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Pandit, S., Cevher, E, Zariwala, M., Somavarapu, S. and Alpar, H.O. 2007. Enhancement of immune response of HBsAg loaded poly(L-lactic acid) microspheres against Hepatitis B through incorporation of alum and chitosan. Journal of Microencapsulation. 24 (6), p. 539–552. https://doi.org/10.1080/02652040701443700

Characterisation of recombinant unglycosylated human serum transferrin purified from Saccharomyces cerevisiae
Sargent, P.J., Farnaud, S., Cammack, R., Zoller, H.M.P. and Evans, R.W. 2006. Characterisation of recombinant unglycosylated human serum transferrin purified from Saccharomyces cerevisiae. BioMetals. 19 (5), pp. 513-519. https://doi.org/10.1007/s10534-005-5532-6

Modelling of a metal-containing hepcidin
Farnaud, S., Patel, A. and Evans, R.W. 2006. Modelling of a metal-containing hepcidin. BioMetals. 19 (5), pp. 527-533. https://doi.org/10.1007/s10534-005-5883-z

Adrenomedullin increases the expression of calcitonin-like receptor and receptor activity modifying protein 2 mRNA in human microvascular endothelial cells
Schwarz, N., Renshaw, D., Kapas, S. and Hinson, J.P. 2006. Adrenomedullin increases the expression of calcitonin-like receptor and receptor activity modifying protein 2 mRNA in human microvascular endothelial cells. Journal of Endocrinology. 190 (2), pp. 505-514. https://doi.org/10.1677/joe.1.06806

Intra-adrenal mechanisms in the response to chronic stress: investigation in a rat model of emotionality
Kosti, O., Raven, P.W., Renshaw, D. and Hinson, J.P. 2006. Intra-adrenal mechanisms in the response to chronic stress: investigation in a rat model of emotionality. Journal of Endocrinology. 189 (2), pp. 211-218. https://doi.org/10.1677/joe.1.06638

An overview of molecular aspects of iron metabolism
Syed, B.A., Sargent, P.J., Farnaud, S. and Evans, R.W. 2006. An overview of molecular aspects of iron metabolism. Hemoglobin. 30 (1), pp. 69-80. https://doi.org/10.1080/03630260500455318

Towards a tree-induction approach to antimicrobial activity analysis of cationic peptides
Farnaud, S., Wang, Z., Dybowski, R., Odell, E.W. and Evans, R.W. 2006. Towards a tree-induction approach to antimicrobial activity analysis of cationic peptides. Biochemistry and Cell Biology. 84 (3), p. 394. https://doi.org/10.1139/O06-900

Structure/function overview of proteins involved in iron storage and transport
Sargent, P.J., Farnaud, S. and Evans, R.W. 2005. Structure/function overview of proteins involved in iron storage and transport. Current Medicinal Chemistry. 12 (23), pp. 2683-2693. https://doi.org/10.2174/092986705774462969

Comparative immunomodulatory properties of a chitosan-MDP adjuvant combination following intranasal or intramuscular immunisation
Moschos, S.A., Bramwell, V.W., Somavarapu, S. and Alpar, H.O. 2005. Comparative immunomodulatory properties of a chitosan-MDP adjuvant combination following intranasal or intramuscular immunisation. Vaccine. 23 (16), pp. 1923-1930. https://doi.org/10.1016/j.vaccine.2004.10.016

Lactoferrin: the conductor of the immunological system?
Farnaud, S. and Evans, R.W. 2005. Lactoferrin: the conductor of the immunological system? in: Veskler, B.A. (ed.) New research on immunology New York Nova Science Publishers.

Adjuvant synergy: the effects of nasal coadministration of adjuvants
Moschos, S.A., Bramwell, V.W., Somavarapu, S. and Alpar, H.O. 2004. Adjuvant synergy: the effects of nasal coadministration of adjuvants. Immunology and Cell Biology. 82 (6), pp. 628-637. https://doi.org/10.1111/j.0818-9641.2004.01280.x

Variation in antimicrobial activity of lactoferricin-derived peptides explained by structure modelling
Farnaud, S., Patel, A., Odell, E.W. and Evans, R.W. 2004. Variation in antimicrobial activity of lactoferricin-derived peptides explained by structure modelling. FEMS Microbiology Letters. 238 (1), pp. 221-226. https://doi.org/10.1111/j.1574-6968.2004.tb09759.x

The plug domain of a neisserial TonB-dependent transporter retains structural integrity in the absence of its transmembrane β-barrel
Oke, M., Sarra, R., Ghirlando, R., Farnaud, S., Gorringe, A.R., Evans, R.W. and Buchanan, S.K. 2004. The plug domain of a neisserial TonB-dependent transporter retains structural integrity in the absence of its transmembrane β-barrel. FEBS Letters. 564 (3), pp. 294-300. https://doi.org/10.1016/S0014-5793(04)00196-6

Interactions of lactoferricin-derived peptides with LPS and antimicrobial activity
Farnaud, S., Spiller, C., Moriarty, L.C., Patel, A., Gant, V., Odell, E.W. and Evans, R.W. 2004. Interactions of lactoferricin-derived peptides with LPS and antimicrobial activity. FEMS Microbiology Letters. 233 (2/29), pp. 193-199. https://doi.org/10.1111/j.1574-6968.2004.tb09482.x

New strategies in vaccine research: targeting quorum sensing pathways for prophylaxis against antibiotic-resistant S. aureus infections
Moschos, S.A., Pandit, S., Somavarapu, S., Balaban, N. and Alpar, H.O. 2004. New strategies in vaccine research: targeting quorum sensing pathways for prophylaxis against antibiotic-resistant S. aureus infections. Proceedings of the 31st International Symposium for the Controlled Release of Bioactive Materials 2004. Honolulu, USA 12 - 16 Jun 2004 pp. 526

Lactoferrin: a multifunctional protein with antimicrobial properties
Farnaud, S. and Evans, R.W. 2003. Lactoferrin: a multifunctional protein with antimicrobial properties. Molecular Immunology. 40 (7), pp. 395-405. https://doi.org/10.1016/S0161-5890(03)00152-4

Bacterial lipopolysaccharide directly stimulates cortisol secretion in human adrenal cells
Vakharia, K., Renshaw, D. and Hinson, J.P. 2002. Bacterial lipopolysaccharide directly stimulates cortisol secretion in human adrenal cells. Endocrine Research. 28 (4), pp. 357-361. https://doi.org/10.1081/ERC-120016809

Bacterial Lipopolysaccharide directly stimulates cortisol secretion in human adrenal cells
Vakharia, K., Renshaw, D. and Hinson, J.P. 2002. Bacterial Lipopolysaccharide directly stimulates cortisol secretion in human adrenal cells. Endocrine Research. 28 (4), pp. 357-361. https://doi.org/10.1081/ERC-120016809

Support for a three-dimensional structure predicting a Cys-Glu-Lys catalytic triad for Pseudomonas aeruginosa amidase comes from site-directed mutagenesis and mutations altering substrate specificity
Novo, C., Farnaud, S., Tata, R., Clemente, A. and Brown, P.R. 2002. Support for a three-dimensional structure predicting a Cys-Glu-Lys catalytic triad for Pseudomonas aeruginosa amidase comes from site-directed mutagenesis and mutations altering substrate specificity. Biochemical Journal. 365 (3), pp. 731-738. https://doi.org/10.1042/BJ20011714

Regulation of rat adrenal vasoactive intestinal peptide content: effects of adrenocorticotropic hormone treatment and changes in dietary sodium intake
Hinson, J.P., Renshaw, D., Carroll, M. and Kapas, S. 2001. Regulation of rat adrenal vasoactive intestinal peptide content: effects of adrenocorticotropic hormone treatment and changes in dietary sodium intake. Journal of Neuroendocrinology. 13 (9), pp. 769-773. https://doi.org/10.1046/j.1365-2826.2001.00692.x

Immunogenicity of adjuvanted recombinant urease administered intranasally
Moschos, S.A., Somavarapu, S., Singh, J., Bramwell, V.W., Randall, L., Guy, B. and Alpar, H.O. 2001. Immunogenicity of adjuvanted recombinant urease administered intranasally. Proceedings of the 28th International Symposium for the Controlled Release of Bioactive Materials. San Diego, USA 23 - 27 Jun 2001 pp. 7033

Immunogenicity of adjuvanted recombinant urease administered intra-muscularly
Moschos, S.A., Somavarapu, S., Eyles, J.E., McHugh, C., Bramwell, V.W., Randall, L., Guy, B. and Alpar, H.O. 2001. Immunogenicity of adjuvanted recombinant urease administered intra-muscularly. Proceedings of the 28th International Symposium for the Controlled Release of Bioactive Materials. San Diego, USA 23 - 27 Jun 2001 pp. 7033

Evaluation of adjuvanted recombinant urease for effective immunization against Helicobacter pylori
Moschos, S.A., Somavarapu, S., Eyles, J.E., McHugh, C., Bramwell, V.W., Randall, L., Guy, B. and Alpar, H.O. 2001. Evaluation of adjuvanted recombinant urease for effective immunization against Helicobacter pylori. Immunology. 104 (s1), p. 98. https://doi.org/10.1046/j.1365-2567.2001.1040s1070.x

Quil-A and MDP enhances the adjuvanticity of alum for intramuscular delivery of rURE
Moschos, S.A., Somavarapu, S., Bramwell, V.W., Randall, L., Guy, B. and Alpar, H.O. 2001. Quil-A and MDP enhances the adjuvanticity of alum for intramuscular delivery of rURE. Immunology. 104 (s1), p. 98. https://doi.org/10.1046/j.1365-2567.2001.1040s1070.x

Microsphere encapsulated Diphtheria Toxoid induces protein secretion from in-vitro Peyers’ patches and in vivo
Turner, J.J., Somavarapu, S., Moschos, S.A., Randall, L., Simpkin, G. and Alpar, H.O. 2000. Microsphere encapsulated Diphtheria Toxoid induces protein secretion from in-vitro Peyers’ patches and in vivo. Proceedings of the 3rd World Meeting APV/APGI 2000. Berlin, Germany 3 - 6 Apr 2000 pp. 389-390

Novel protein secretion from both ex-vivo Peyers’ patches and in-vivo; induction by microsphere encapsulated diphtheria toxoid
Moschos, S.A., Somavarapu, S., Singh, J., Bramwell, V.W., Randall, L., Guy, B. and Alpar, H.O. 2000. Novel protein secretion from both ex-vivo Peyers’ patches and in-vivo; induction by microsphere encapsulated diphtheria toxoid. Proceedings of the 27th International Symposium for the Controlled Release of Bioactive Materials. Paris, France 09 - 13 Jul 2001 pp. 562-563

Evidence that cysteine-166 is the active-site nucleophile of Pseudomonas aeruginosa amidase: crystallization and preliminary X-ray diffraction analysis of the enzyme
Farnaud, S., Tata, R., Sohi, M.K., Wan, T., Brown, P.R. and Sutton, B.J. 1999. Evidence that cysteine-166 is the active-site nucleophile of Pseudomonas aeruginosa amidase: crystallization and preliminary X-ray diffraction analysis of the enzyme. Biochemical Journal. 340 (3), pp. 711-714.

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