The Experts below are selected from a list of 1455 Experts worldwide ranked by ideXlab platform
Ben J. Boyd - One of the best experts on this subject based on the ideXlab platform.
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steric stabilisers govern the colloidal and chemical stability but not in vitro cellular toxicity of linoleoylethanolamide Cubosomes
Colloids and Surfaces B: Biointerfaces, 2020Co-Authors: Younus Mohammad, Ben J. Boyd, Anita B Fallah, John N J Reynolds, Shakila B. RizwanAbstract:Linoleoylethanolamide (LEA) is an endogenous lipid with remarkable neuromodulatory properties. However, its therapeutic potential is limited by rapid clearance in vivo, targetability and solubility. This study aimed to formulate LEA into liquid crystalline nanoparticles (Cubosomes) as a strategy to address the aforementioned challenges. The influence of three different steric stabilisers: Tween 80 and Pluronic F68, both of which have the potential to interact with receptors expressed at the blood-brain barrier and Pluronic F127 as a control, on colloidal stability, internal structure, chemical stability and cytotoxicity of the dispersions were investigated. We found that for effective stabilization of LEA dispersions, a higher concentration of Tween 80 was required compared to Pluronics. Freshly prepared dispersions showed mean particle size of <250 nm and low PDIs (<0.2), with an Im3m type cubic structure but with different lattice parameters. Upon storage at ambient temperature for a week, increased mean particle size and PDI, with a significant reduction in the concentration of LEA was observed in Tween 80-stabilised dispersions. Greater than 80% cell viability was observed at concentrations of up to 20 μg/mL LEA in the presence of all three stabilisers. Collectively, our results suggest that the stabiliser type influences colloidal and chemical stability but not cytotoxicity of LEA Cubosomes. This study highlights the potential of endogenous bioactive lipids to be utilized as core cubosome forming lipids with the view to improving their solubility, rapid clearance and targetability to enable delivery of these bioactive molecules to the brain.
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spray dried Cubosomes with ovalbumin and quil a as a nanoparticulate dry powder vaccine formulation
International Journal of Pharmaceutics, 2018Co-Authors: Christoffer Von Halling Laier, Ben J. Boyd, Sarah Hook, Thomas Rades, Anja Boisen, Blake Gibson, Marco Van De Weert, Line Hagner NielsenAbstract:: Subunit vaccine formulations are often produced as liquid dispersions through complicated processes. It is desirable, however, to have simple, cheap and up-scalable methods to produce nanoparticulate subunit vaccines in powder form. Here, a simple single-step spray drying process for production of powder cubosome precursors with the model antigen ovalbumin (OVA) and the adjuvant Quil-A is presented. The Cubosomes were characterized in vitro and evaluated in vivo by subcutaneous and oral administration for their potential as a vaccine formulation. Hydrated Cubosomes had average particle size of 257 ± 8 nm and zeta potential of -18.0 ± 0.6 mV. The powder contained 10.6 ± 0.7% w/w OVA prior to hydration, of which 65 ± 1% was released within the first 20 min in 9.5 mM PBS at pH 7.3, with the remaining OVA gradually released over the following 24 h. Immunization with Cubosomes resulted in significantly stronger antigen-specific serum IgG responses (p < 0.01), CD8+ T cell expansion (p < 0.0001) and target T cell killing compared to controls when given s.c., and was ineffective orally. This study shows that spray drying is a suitable method for producing nanoparticulate vaccine formulations in dry powder form.
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Spray dried Cubosomes with ovalbumin and Quil-A as a nanoparticulate dry powder vaccine formulation
International Journal of Pharmaceutics, 2018Co-Authors: Christoffer Von Halling Laier, Ben J. Boyd, Sarah Hook, Thomas Rades, Anja Boisen, Blake Gibson, Marco Van De Weert, Line Hagner NielsenAbstract:Subunit vaccine formulations are often produced as liquid dispersions through complicated processes. It is desirable, however, to have simple, cheap and up-scalable methods to produce nanoparticulate subunit vaccines in powder form. Here, a simple single-step spray drying process for production of powder cubosome precursors with the model antigen ovalbumin (OVA) and the adjuvant Quil-A is presented. The Cubosomes were characterized in vitro and evaluated in vivo by subcutaneous and oral administration for their potential as a vaccine formulation. Hydrated Cubosomes had average particle size of 257 ± 8 nm and zeta potential of -18.0 ± 0.6 mV. The powder contained 10.6 ± 0.7% w/w OVA prior to hydration, of which 65 ± 1% was released within the first 20 min in 9.5 mM PBS at pH 7.3, with the remaining OVA gradually released over the following 24 h. Immunization with Cubosomes resulted in significantly stronger antigen-specific serum IgG responses (p
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Clickable Cubosomes for Antibody-Free Drug Targeting and Imaging Applications
Bioconjugate Chemistry, 2017Co-Authors: Nicolas Alcaraz, Angus P. R. Johnston, Eric Hanssen, Ben J. BoydAbstract:The combination of copper-free click chemistry with metabolic labeling offers new opportunities in drug delivery. The objective of this study was to determine whether Cubosomes functionalized with azide or dibenzocyclooctyne (DBCO) groups are able to undergo copper-free click chemistry with a strained cyclooctyne or azide, respectively. Phytantriol-based Cubosomes were functionalized using phospholipids bearing an azide or DBCO group. The modified cubosome dispersions were characterized using dynamic light scattering, cryo-TEM, and small-angle X-ray scattering. The efficiency of “clickability” was assessed by reacting the Cubosomes with a complementary dye and determining bound and unbound dye via size exclusion chromatography. The clickable Cubosomes reacted specifically and efficiently with a click-Cy5 dye with minor changes to the size, shape, and structure of the Cubosomes. This indicates that Cubosomes can retain their unique internal structure while participating in copper-free click chemistry. This...
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Microcontainers as an oral delivery system for spray dried Cubosomes containing ovalbumin.
European Journal of Pharmaceutics and Biopharmaceutics, 2017Co-Authors: Line Hagner Nielsen, Ben J. Boyd, Thomas Rades, Anja BoisenAbstract:Abstract The purpose of this study was to prepare Cubosomes encapsulating the model antigen ovalbumin (OVA) via spray drying, and to characterise such Cubosomes with a view for their potential application in oral vaccine delivery. Furthermore the cubosome formulation was loaded into polymeric microcontainers intended as an oral drug delivery system. The Cubosomes consisted of commercial glyceryl monooleate, Dimodan®, containing OVA and were surrounded with a dextran shell prepared by spray drying. Cryo-TEM was used to confirm that Cubosomes were formed after hydration of the spray dried precursor powder. The precursor powder had a mean particle size of 1.3 ± 0.1 μm, whereas the mean diameter of the dispersed Cubosomes was 282 ± 7 nm (PDI: 0.18) measured by dynamic light scattering. 8.5 ± 0.3% (w/w) of OVA was present in the cubosome powder and OVA was found released slowly over the first 70 h, followed by a more rapid release. Total release of 47.9 ± 2.8% of loaded OVA occurred over 96 h in a buffer at pH 6.8. When the powder was filled into microcontainers, and the opening covered with the pH sensitive polymer Eudragit S100, the pH sensitive ‘lid’ was intact at gastric pH, but release of OVA from the Cubosomes and microcontainers occurred at pH 6.8, releasing 44.1 ± 5.6% of the OVA in 96 h. Small-angle X-ray scattering (SAXS) revealed that the ‘dry’ particles possessed an internal ordered lipid structure (lamellar and inverse micellar phase) by virtue of a small amount of residual water, and after hydration in buffer at pH 6.8, the particles formed the hexagonal inverse cubic phases, thereby indicating that Cubosomes were formed when released from microcontainers.
Shakila B. Rizwan - One of the best experts on this subject based on the ideXlab platform.
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steric stabilisers govern the colloidal and chemical stability but not in vitro cellular toxicity of linoleoylethanolamide Cubosomes
Colloids and Surfaces B: Biointerfaces, 2020Co-Authors: Younus Mohammad, Ben J. Boyd, Anita B Fallah, John N J Reynolds, Shakila B. RizwanAbstract:Linoleoylethanolamide (LEA) is an endogenous lipid with remarkable neuromodulatory properties. However, its therapeutic potential is limited by rapid clearance in vivo, targetability and solubility. This study aimed to formulate LEA into liquid crystalline nanoparticles (Cubosomes) as a strategy to address the aforementioned challenges. The influence of three different steric stabilisers: Tween 80 and Pluronic F68, both of which have the potential to interact with receptors expressed at the blood-brain barrier and Pluronic F127 as a control, on colloidal stability, internal structure, chemical stability and cytotoxicity of the dispersions were investigated. We found that for effective stabilization of LEA dispersions, a higher concentration of Tween 80 was required compared to Pluronics. Freshly prepared dispersions showed mean particle size of <250 nm and low PDIs (<0.2), with an Im3m type cubic structure but with different lattice parameters. Upon storage at ambient temperature for a week, increased mean particle size and PDI, with a significant reduction in the concentration of LEA was observed in Tween 80-stabilised dispersions. Greater than 80% cell viability was observed at concentrations of up to 20 μg/mL LEA in the presence of all three stabilisers. Collectively, our results suggest that the stabiliser type influences colloidal and chemical stability but not cytotoxicity of LEA Cubosomes. This study highlights the potential of endogenous bioactive lipids to be utilized as core cubosome forming lipids with the view to improving their solubility, rapid clearance and targetability to enable delivery of these bioactive molecules to the brain.
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incorporation of an endogenous neuromodulatory lipid oleoylethanolamide into Cubosomes nanostructural characterization
Langmuir, 2016Co-Authors: Mohammad Younus, Ben J. Boyd, Richard N Prentice, Andrew N Clarkson, Shakila B. RizwanAbstract:Oleoylethanolamide (OEA) is an endogenous lipid with neuroprotective properties and the fortification of its concentration in the brain can be beneficial in the treatment of many neurodegenerative disorders. However, OEA is rapidly eliminated by hydrolysis in vivo, limiting its therapeutic potential. We hypothesize that packing OEA within a nanoparticulate system such as Cubosomes, which can be used to target the blood–brain barrier (BBB), will protect it against hydrolysis and enable therapeutic concentrations to reach the brain. Cubosomes are lipid-based nanoparticles with a unique bicontinuous cubic phase internal structure. In the present study, the incorporation and chemical stability of OEA in Cubosomes was investigated. Cubosomes containing OEA had a mean particle size of less than 200 nm with low polydispersity (polydispersity index <0.25). Infrared spectroscopy and high-performance liquid chromatography showed chemical stability and the encapsulation of OEA within Cubosomes. Cryo-TEM and SAXS mea...
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Stabilising Cubosomes with Tween 80 as a step towards targeting lipid nanocarriers to the blood-brain barrier.
European Journal of Pharmaceutics and Biopharmaceutics, 2016Co-Authors: Hanisah Azhari, Ben J. Boyd, Michael A. Strauss, Sarah Hook, Shakila B. RizwanAbstract:Coating nanoparticles with the surfactant Tween 80 have been previously shown to enhance drug delivery across the blood-brain barrier (BBB). The aim of this study was to investigate whether Tween 80 could be used to stabilise phytantriol-based Cubosomes thereby enabling potential application in delivering macromolecular therapeutics to the brain. Cubosome particles with their large internal and external surface area by virtue of their nanostructure are ideal for delivery of macromolecules. Phase behaviour studies were conducted using a combination of optical microscopy and small-angle X-ray scattering (SAXS) and the addition of Tween 80 to mixtures of phytantriol and water resulted in a rich array of lyotropic mesophases. In particular, a large cubic phase region and a two-phase region of readily dispersed Cubosomes is observed. Cubosomes with different concentrations of Tween 80 and phytantriol as the liquid crystal forming lipid were prepared using the solvent precursor method and their physical properties were investigated. A combination of dynamic light scattering, cryogenic electron tomography and SAXS shows formation of well-defined Cubosomes with a narrow size distribution and the Im3m cubic structure. Collectively, the results confirm that Tween 80 can effectively stabilize phytantriol Cubosomes, opening the possibility for future application in drug delivery across the BBB. Moreover, well-defined, homogenous cubosome formulations prepared using the mild solvent precursor dilution method has significant implications for large-scale production of Cubosomes, which currently is a major barrier to the application of Cubosomes in the clinic.
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Cubosomes containing the adjuvants imiquimod and monophosphoryl lipid A stimulate robust cellular and humoral immune responses.
Journal of Controlled Release, 2013Co-Authors: Shakila B. Rizwan, Thomas Rades, Warren T. Mcburney, Katie Young, Tracey Hanley, Benjamin James Boyd, Sarah HookAbstract:Abstract New generation vaccines increasingly utilize highly purified peptides and proteins as the target antigen, however these are often poorly immunogenic. One of the most promising strategies for improving immunogenicity of such subunit vaccines is through incorporation into particulate carriers. Here we report the preparation, physicochemical characterization and in vivo immunological activity of Cubosomes, a novel lipid-based nanostructured particulate carrier, modified to include the Toll-like receptor agonists monophosphoryl lipid A and imiquimod. The immunological activity of cubosome formulations was compared to that of liposome and alum formulations. Sustained release of the model antigen ovalbumin (Ova) was observed in vitro and in vivo from Cubosomes. Cubosomes + adjuvants induced robust CD8 + and CD4 + T cell proliferation and interferon-γ production, as well as the production of Ova-specific antibodies. Cubosomes + adjuvants were more efficient at generating Ova-specific cellular responses and were equally as effective in generating humoral responses when compared to liposomes + adjuvants and alum. Overall, the results show that Cubosomes have the potential to act as effective sustained release vaccine delivery systems.
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development and characterisation of modified poloxamer 407 thermoresponsive depot systems containing Cubosomes
International Journal of Pharmaceutics, 2011Co-Authors: Thunjiradasiree Kojarunchitt, Sarah Hook, Shakila B. Rizwan, Thomas Rades, Stefania BaldursdottirAbstract:Abstract The purpose of this study is to develop a thermoresponsive sustained release delivery system combining phytantriol Cubosomes and poloxamer 407 (P407). P407 undergoes thermoreversible gelation, where it exists as a free-flowing liquid at low temperature and gels upon heating. However, this polymer has the major draw back of fast erosion in aqueous environments which needs to be addressed. Three different concentrations of P407 (12%, 15% and 17% (w/v)) were formulated with various additives (methyl cellulose (MC), dextran, carrageenan and Pluronic-R (25R4)). The rheological characteristics and in vitro stability were investigated. The sol–gel transition temperature of P407 was lowered in the presence of the phytantriol Cubosomes. The addition of MC and dextran did not affect the sol–gel transition temperature whereas 25R4 increased the gelation temperature. No transition was observed for the carrageenan formulations. The presence of 25R4 allowed the development of formulations that were free flowing liquid at working temperature (22 °C), gelled at body temperature (37 °C) and had improved stability in an aqueous environment. Both rheological and in vitro stability studies suggested that cubosome-loaded 17% (w/v) P407 with 25R4 in 1:1 molar ratio may have a potential as sustained release delivery system.
Sarah Hook - One of the best experts on this subject based on the ideXlab platform.
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spray dried Cubosomes with ovalbumin and quil a as a nanoparticulate dry powder vaccine formulation
International Journal of Pharmaceutics, 2018Co-Authors: Christoffer Von Halling Laier, Ben J. Boyd, Sarah Hook, Thomas Rades, Anja Boisen, Blake Gibson, Marco Van De Weert, Line Hagner NielsenAbstract:: Subunit vaccine formulations are often produced as liquid dispersions through complicated processes. It is desirable, however, to have simple, cheap and up-scalable methods to produce nanoparticulate subunit vaccines in powder form. Here, a simple single-step spray drying process for production of powder cubosome precursors with the model antigen ovalbumin (OVA) and the adjuvant Quil-A is presented. The Cubosomes were characterized in vitro and evaluated in vivo by subcutaneous and oral administration for their potential as a vaccine formulation. Hydrated Cubosomes had average particle size of 257 ± 8 nm and zeta potential of -18.0 ± 0.6 mV. The powder contained 10.6 ± 0.7% w/w OVA prior to hydration, of which 65 ± 1% was released within the first 20 min in 9.5 mM PBS at pH 7.3, with the remaining OVA gradually released over the following 24 h. Immunization with Cubosomes resulted in significantly stronger antigen-specific serum IgG responses (p < 0.01), CD8+ T cell expansion (p < 0.0001) and target T cell killing compared to controls when given s.c., and was ineffective orally. This study shows that spray drying is a suitable method for producing nanoparticulate vaccine formulations in dry powder form.
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Spray dried Cubosomes with ovalbumin and Quil-A as a nanoparticulate dry powder vaccine formulation
International Journal of Pharmaceutics, 2018Co-Authors: Christoffer Von Halling Laier, Ben J. Boyd, Sarah Hook, Thomas Rades, Anja Boisen, Blake Gibson, Marco Van De Weert, Line Hagner NielsenAbstract:Subunit vaccine formulations are often produced as liquid dispersions through complicated processes. It is desirable, however, to have simple, cheap and up-scalable methods to produce nanoparticulate subunit vaccines in powder form. Here, a simple single-step spray drying process for production of powder cubosome precursors with the model antigen ovalbumin (OVA) and the adjuvant Quil-A is presented. The Cubosomes were characterized in vitro and evaluated in vivo by subcutaneous and oral administration for their potential as a vaccine formulation. Hydrated Cubosomes had average particle size of 257 ± 8 nm and zeta potential of -18.0 ± 0.6 mV. The powder contained 10.6 ± 0.7% w/w OVA prior to hydration, of which 65 ± 1% was released within the first 20 min in 9.5 mM PBS at pH 7.3, with the remaining OVA gradually released over the following 24 h. Immunization with Cubosomes resulted in significantly stronger antigen-specific serum IgG responses (p
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Stabilising Cubosomes with Tween 80 as a step towards targeting lipid nanocarriers to the blood-brain barrier.
European Journal of Pharmaceutics and Biopharmaceutics, 2016Co-Authors: Hanisah Azhari, Ben J. Boyd, Michael A. Strauss, Sarah Hook, Shakila B. RizwanAbstract:Coating nanoparticles with the surfactant Tween 80 have been previously shown to enhance drug delivery across the blood-brain barrier (BBB). The aim of this study was to investigate whether Tween 80 could be used to stabilise phytantriol-based Cubosomes thereby enabling potential application in delivering macromolecular therapeutics to the brain. Cubosome particles with their large internal and external surface area by virtue of their nanostructure are ideal for delivery of macromolecules. Phase behaviour studies were conducted using a combination of optical microscopy and small-angle X-ray scattering (SAXS) and the addition of Tween 80 to mixtures of phytantriol and water resulted in a rich array of lyotropic mesophases. In particular, a large cubic phase region and a two-phase region of readily dispersed Cubosomes is observed. Cubosomes with different concentrations of Tween 80 and phytantriol as the liquid crystal forming lipid were prepared using the solvent precursor method and their physical properties were investigated. A combination of dynamic light scattering, cryogenic electron tomography and SAXS shows formation of well-defined Cubosomes with a narrow size distribution and the Im3m cubic structure. Collectively, the results confirm that Tween 80 can effectively stabilize phytantriol Cubosomes, opening the possibility for future application in drug delivery across the BBB. Moreover, well-defined, homogenous cubosome formulations prepared using the mild solvent precursor dilution method has significant implications for large-scale production of Cubosomes, which currently is a major barrier to the application of Cubosomes in the clinic.
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Cubosomes containing the adjuvants imiquimod and monophosphoryl lipid A stimulate robust cellular and humoral immune responses.
Journal of Controlled Release, 2013Co-Authors: Shakila B. Rizwan, Thomas Rades, Warren T. Mcburney, Katie Young, Tracey Hanley, Benjamin James Boyd, Sarah HookAbstract:Abstract New generation vaccines increasingly utilize highly purified peptides and proteins as the target antigen, however these are often poorly immunogenic. One of the most promising strategies for improving immunogenicity of such subunit vaccines is through incorporation into particulate carriers. Here we report the preparation, physicochemical characterization and in vivo immunological activity of Cubosomes, a novel lipid-based nanostructured particulate carrier, modified to include the Toll-like receptor agonists monophosphoryl lipid A and imiquimod. The immunological activity of cubosome formulations was compared to that of liposome and alum formulations. Sustained release of the model antigen ovalbumin (Ova) was observed in vitro and in vivo from Cubosomes. Cubosomes + adjuvants induced robust CD8 + and CD4 + T cell proliferation and interferon-γ production, as well as the production of Ova-specific antibodies. Cubosomes + adjuvants were more efficient at generating Ova-specific cellular responses and were equally as effective in generating humoral responses when compared to liposomes + adjuvants and alum. Overall, the results show that Cubosomes have the potential to act as effective sustained release vaccine delivery systems.
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Transcutaneous immunization using microneedles and Cubosomes: Mechanistic investigations using Optical Coherence Tomography and Two-Photon Microscopy.
Journal of Controlled Release, 2013Co-Authors: Teerawan Rattanapak, Thomas Rades, James Caradoc Birchall, Katherine Young, Masaru Ishii, Igor Meglinski, Sarah HookAbstract:Transcutaneous (TCI) immunization is a novel vaccination approach that provides many advantages over traditional parenteral vaccination. However, a major barrier to TCI is mediating penetration of vaccine antigens through the stratum corneum (SC) to the deeper tissue layers. Many approaches have been investigated for enhancing drug penetration into the skin including microneedles (MNs) to transiently breach the SC barrier and incorporation of vaccines into penetration-enhancing delivery systems. This study utilized MNs and a lipid-based colloidal delivery system (Cubosomes) as a synergistic approach for the delivery of vaccines through the skin. The penetration and permeation of the peptide antigen into and through skin were analysed quantitatively and qualitatively using techniques including Optical Coherence Tomography and two-photon microscopy. It was found that while the use of MNs increased the permeation of an aqueous peptide mixture through skin, cubosome-formulated peptide and Cubosomes were retained in the skin. Therefore, it is proposed that a combined approach using MNs and Cubosomes will be an efficient system for the local delivery of antigen to immunocompetent cells in the skin.
Thomas Rades - One of the best experts on this subject based on the ideXlab platform.
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spray dried Cubosomes with ovalbumin and quil a as a nanoparticulate dry powder vaccine formulation
International Journal of Pharmaceutics, 2018Co-Authors: Christoffer Von Halling Laier, Ben J. Boyd, Sarah Hook, Thomas Rades, Anja Boisen, Blake Gibson, Marco Van De Weert, Line Hagner NielsenAbstract:: Subunit vaccine formulations are often produced as liquid dispersions through complicated processes. It is desirable, however, to have simple, cheap and up-scalable methods to produce nanoparticulate subunit vaccines in powder form. Here, a simple single-step spray drying process for production of powder cubosome precursors with the model antigen ovalbumin (OVA) and the adjuvant Quil-A is presented. The Cubosomes were characterized in vitro and evaluated in vivo by subcutaneous and oral administration for their potential as a vaccine formulation. Hydrated Cubosomes had average particle size of 257 ± 8 nm and zeta potential of -18.0 ± 0.6 mV. The powder contained 10.6 ± 0.7% w/w OVA prior to hydration, of which 65 ± 1% was released within the first 20 min in 9.5 mM PBS at pH 7.3, with the remaining OVA gradually released over the following 24 h. Immunization with Cubosomes resulted in significantly stronger antigen-specific serum IgG responses (p < 0.01), CD8+ T cell expansion (p < 0.0001) and target T cell killing compared to controls when given s.c., and was ineffective orally. This study shows that spray drying is a suitable method for producing nanoparticulate vaccine formulations in dry powder form.
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Spray dried Cubosomes with ovalbumin and Quil-A as a nanoparticulate dry powder vaccine formulation
International Journal of Pharmaceutics, 2018Co-Authors: Christoffer Von Halling Laier, Ben J. Boyd, Sarah Hook, Thomas Rades, Anja Boisen, Blake Gibson, Marco Van De Weert, Line Hagner NielsenAbstract:Subunit vaccine formulations are often produced as liquid dispersions through complicated processes. It is desirable, however, to have simple, cheap and up-scalable methods to produce nanoparticulate subunit vaccines in powder form. Here, a simple single-step spray drying process for production of powder cubosome precursors with the model antigen ovalbumin (OVA) and the adjuvant Quil-A is presented. The Cubosomes were characterized in vitro and evaluated in vivo by subcutaneous and oral administration for their potential as a vaccine formulation. Hydrated Cubosomes had average particle size of 257 ± 8 nm and zeta potential of -18.0 ± 0.6 mV. The powder contained 10.6 ± 0.7% w/w OVA prior to hydration, of which 65 ± 1% was released within the first 20 min in 9.5 mM PBS at pH 7.3, with the remaining OVA gradually released over the following 24 h. Immunization with Cubosomes resulted in significantly stronger antigen-specific serum IgG responses (p
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Microcontainers as an oral delivery system for spray dried Cubosomes containing ovalbumin.
European Journal of Pharmaceutics and Biopharmaceutics, 2017Co-Authors: Line Hagner Nielsen, Ben J. Boyd, Thomas Rades, Anja BoisenAbstract:Abstract The purpose of this study was to prepare Cubosomes encapsulating the model antigen ovalbumin (OVA) via spray drying, and to characterise such Cubosomes with a view for their potential application in oral vaccine delivery. Furthermore the cubosome formulation was loaded into polymeric microcontainers intended as an oral drug delivery system. The Cubosomes consisted of commercial glyceryl monooleate, Dimodan®, containing OVA and were surrounded with a dextran shell prepared by spray drying. Cryo-TEM was used to confirm that Cubosomes were formed after hydration of the spray dried precursor powder. The precursor powder had a mean particle size of 1.3 ± 0.1 μm, whereas the mean diameter of the dispersed Cubosomes was 282 ± 7 nm (PDI: 0.18) measured by dynamic light scattering. 8.5 ± 0.3% (w/w) of OVA was present in the cubosome powder and OVA was found released slowly over the first 70 h, followed by a more rapid release. Total release of 47.9 ± 2.8% of loaded OVA occurred over 96 h in a buffer at pH 6.8. When the powder was filled into microcontainers, and the opening covered with the pH sensitive polymer Eudragit S100, the pH sensitive ‘lid’ was intact at gastric pH, but release of OVA from the Cubosomes and microcontainers occurred at pH 6.8, releasing 44.1 ± 5.6% of the OVA in 96 h. Small-angle X-ray scattering (SAXS) revealed that the ‘dry’ particles possessed an internal ordered lipid structure (lamellar and inverse micellar phase) by virtue of a small amount of residual water, and after hydration in buffer at pH 6.8, the particles formed the hexagonal inverse cubic phases, thereby indicating that Cubosomes were formed when released from microcontainers.
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Cubosomes containing the adjuvants imiquimod and monophosphoryl lipid A stimulate robust cellular and humoral immune responses.
Journal of Controlled Release, 2013Co-Authors: Shakila B. Rizwan, Thomas Rades, Warren T. Mcburney, Katie Young, Tracey Hanley, Benjamin James Boyd, Sarah HookAbstract:Abstract New generation vaccines increasingly utilize highly purified peptides and proteins as the target antigen, however these are often poorly immunogenic. One of the most promising strategies for improving immunogenicity of such subunit vaccines is through incorporation into particulate carriers. Here we report the preparation, physicochemical characterization and in vivo immunological activity of Cubosomes, a novel lipid-based nanostructured particulate carrier, modified to include the Toll-like receptor agonists monophosphoryl lipid A and imiquimod. The immunological activity of cubosome formulations was compared to that of liposome and alum formulations. Sustained release of the model antigen ovalbumin (Ova) was observed in vitro and in vivo from Cubosomes. Cubosomes + adjuvants induced robust CD8 + and CD4 + T cell proliferation and interferon-γ production, as well as the production of Ova-specific antibodies. Cubosomes + adjuvants were more efficient at generating Ova-specific cellular responses and were equally as effective in generating humoral responses when compared to liposomes + adjuvants and alum. Overall, the results show that Cubosomes have the potential to act as effective sustained release vaccine delivery systems.
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Transcutaneous immunization using microneedles and Cubosomes: Mechanistic investigations using Optical Coherence Tomography and Two-Photon Microscopy.
Journal of Controlled Release, 2013Co-Authors: Teerawan Rattanapak, Thomas Rades, James Caradoc Birchall, Katherine Young, Masaru Ishii, Igor Meglinski, Sarah HookAbstract:Transcutaneous (TCI) immunization is a novel vaccination approach that provides many advantages over traditional parenteral vaccination. However, a major barrier to TCI is mediating penetration of vaccine antigens through the stratum corneum (SC) to the deeper tissue layers. Many approaches have been investigated for enhancing drug penetration into the skin including microneedles (MNs) to transiently breach the SC barrier and incorporation of vaccines into penetration-enhancing delivery systems. This study utilized MNs and a lipid-based colloidal delivery system (Cubosomes) as a synergistic approach for the delivery of vaccines through the skin. The penetration and permeation of the peptide antigen into and through skin were analysed quantitatively and qualitatively using techniques including Optical Coherence Tomography and two-photon microscopy. It was found that while the use of MNs increased the permeation of an aqueous peptide mixture through skin, cubosome-formulated peptide and Cubosomes were retained in the skin. Therefore, it is proposed that a combined approach using MNs and Cubosomes will be an efficient system for the local delivery of antigen to immunocompetent cells in the skin.
Line Hagner Nielsen - One of the best experts on this subject based on the ideXlab platform.
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spray dried Cubosomes with ovalbumin and quil a as a nanoparticulate dry powder vaccine formulation
International Journal of Pharmaceutics, 2018Co-Authors: Christoffer Von Halling Laier, Ben J. Boyd, Sarah Hook, Thomas Rades, Anja Boisen, Blake Gibson, Marco Van De Weert, Line Hagner NielsenAbstract:: Subunit vaccine formulations are often produced as liquid dispersions through complicated processes. It is desirable, however, to have simple, cheap and up-scalable methods to produce nanoparticulate subunit vaccines in powder form. Here, a simple single-step spray drying process for production of powder cubosome precursors with the model antigen ovalbumin (OVA) and the adjuvant Quil-A is presented. The Cubosomes were characterized in vitro and evaluated in vivo by subcutaneous and oral administration for their potential as a vaccine formulation. Hydrated Cubosomes had average particle size of 257 ± 8 nm and zeta potential of -18.0 ± 0.6 mV. The powder contained 10.6 ± 0.7% w/w OVA prior to hydration, of which 65 ± 1% was released within the first 20 min in 9.5 mM PBS at pH 7.3, with the remaining OVA gradually released over the following 24 h. Immunization with Cubosomes resulted in significantly stronger antigen-specific serum IgG responses (p < 0.01), CD8+ T cell expansion (p < 0.0001) and target T cell killing compared to controls when given s.c., and was ineffective orally. This study shows that spray drying is a suitable method for producing nanoparticulate vaccine formulations in dry powder form.
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Spray dried Cubosomes with ovalbumin and Quil-A as a nanoparticulate dry powder vaccine formulation
International Journal of Pharmaceutics, 2018Co-Authors: Christoffer Von Halling Laier, Ben J. Boyd, Sarah Hook, Thomas Rades, Anja Boisen, Blake Gibson, Marco Van De Weert, Line Hagner NielsenAbstract:Subunit vaccine formulations are often produced as liquid dispersions through complicated processes. It is desirable, however, to have simple, cheap and up-scalable methods to produce nanoparticulate subunit vaccines in powder form. Here, a simple single-step spray drying process for production of powder cubosome precursors with the model antigen ovalbumin (OVA) and the adjuvant Quil-A is presented. The Cubosomes were characterized in vitro and evaluated in vivo by subcutaneous and oral administration for their potential as a vaccine formulation. Hydrated Cubosomes had average particle size of 257 ± 8 nm and zeta potential of -18.0 ± 0.6 mV. The powder contained 10.6 ± 0.7% w/w OVA prior to hydration, of which 65 ± 1% was released within the first 20 min in 9.5 mM PBS at pH 7.3, with the remaining OVA gradually released over the following 24 h. Immunization with Cubosomes resulted in significantly stronger antigen-specific serum IgG responses (p
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Microcontainers as an oral delivery system for spray dried Cubosomes containing ovalbumin.
European Journal of Pharmaceutics and Biopharmaceutics, 2017Co-Authors: Line Hagner Nielsen, Ben J. Boyd, Thomas Rades, Anja BoisenAbstract:Abstract The purpose of this study was to prepare Cubosomes encapsulating the model antigen ovalbumin (OVA) via spray drying, and to characterise such Cubosomes with a view for their potential application in oral vaccine delivery. Furthermore the cubosome formulation was loaded into polymeric microcontainers intended as an oral drug delivery system. The Cubosomes consisted of commercial glyceryl monooleate, Dimodan®, containing OVA and were surrounded with a dextran shell prepared by spray drying. Cryo-TEM was used to confirm that Cubosomes were formed after hydration of the spray dried precursor powder. The precursor powder had a mean particle size of 1.3 ± 0.1 μm, whereas the mean diameter of the dispersed Cubosomes was 282 ± 7 nm (PDI: 0.18) measured by dynamic light scattering. 8.5 ± 0.3% (w/w) of OVA was present in the cubosome powder and OVA was found released slowly over the first 70 h, followed by a more rapid release. Total release of 47.9 ± 2.8% of loaded OVA occurred over 96 h in a buffer at pH 6.8. When the powder was filled into microcontainers, and the opening covered with the pH sensitive polymer Eudragit S100, the pH sensitive ‘lid’ was intact at gastric pH, but release of OVA from the Cubosomes and microcontainers occurred at pH 6.8, releasing 44.1 ± 5.6% of the OVA in 96 h. Small-angle X-ray scattering (SAXS) revealed that the ‘dry’ particles possessed an internal ordered lipid structure (lamellar and inverse micellar phase) by virtue of a small amount of residual water, and after hydration in buffer at pH 6.8, the particles formed the hexagonal inverse cubic phases, thereby indicating that Cubosomes were formed when released from microcontainers.