Synthesis of biodegradable polymer-mesoporous silica composite microspheres for DNA prime-protein boost vaccination
DNA vaccines or proteins are capable of inducing specific immunity; however, the translation to the clinic has generally been problematic, primarily due to the reduced magnitude of immune response and poor pharmacokinetics. Herein we demonstrate a composite microsphere formulation, composed of mesop...
| Main Authors: | , , , , |
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| Format: | Journal Article |
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Elsevier Science
2010
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| Online Access: | http://hdl.handle.net/20.500.11937/17451 |
| _version_ | 1848749469740302336 |
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| author | Ho, J. Huang, Y. Danquah, Michael Wang, H. Forde, G. |
| author_facet | Ho, J. Huang, Y. Danquah, Michael Wang, H. Forde, G. |
| author_sort | Ho, J. |
| building | Curtin Institutional Repository |
| collection | Online Access |
| description | DNA vaccines or proteins are capable of inducing specific immunity; however, the translation to the clinic has generally been problematic, primarily due to the reduced magnitude of immune response and poor pharmacokinetics. Herein we demonstrate a composite microsphere formulation, composed of mesoporous silica spheres (MPS) and poly(d,l-lactide-co-glycolide) (PLGA), enables the controlled delivery of a prime-boost vaccine via the encapsulation of plasmid DNA (pDNA) and protein in different compartments. Method with modified dual-concentric-feeding needles attached to a 40 kHz ultrasonic atomizer was studied. These needles focus the flow of two different solutions, which passed through the ultrasonic atomizer. The process synthesis parameters, which are important to the scale-up of composite microspheres, were also studied. These parameters include polymer concentration, feed flowrate, and volumetric ratio of polymer and pDNA-PEI/MPS-BSA. This fabrication technique produced composite microspheres with mean D[4,3] ranging from 6 to 34 µm, depending upon the microsphere preparation. The resultant physical morphology of composite microspheres was largely influenced by the volumetric ratio of pDNA-PEI/MPS-BSA to polymer, and this was due to the precipitation of MPS at the surface of the microspheres. The encapsulation efficiencies were predominantly in the range of 93-98% for pDNA and 46-68% for MPS. In the in vitro studies, the pDNA and protein showed different release kinetics in a 40 day time frame. The dual-concentric-feeding in ultrasonic atomization was shown to have excellent reproducibility. It was concluded that this fabrication technique is an effective method to prepare formulations containing a heterologous prime-boost vaccine in a single delivery system. © 2010 Elsevier B.V. All rights reserved. |
| first_indexed | 2025-11-14T07:21:26Z |
| format | Journal Article |
| id | curtin-20.500.11937-17451 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| last_indexed | 2025-11-14T07:21:26Z |
| publishDate | 2010 |
| publisher | Elsevier Science |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | curtin-20.500.11937-174512017-09-13T15:44:15Z Synthesis of biodegradable polymer-mesoporous silica composite microspheres for DNA prime-protein boost vaccination Ho, J. Huang, Y. Danquah, Michael Wang, H. Forde, G. DNA vaccines or proteins are capable of inducing specific immunity; however, the translation to the clinic has generally been problematic, primarily due to the reduced magnitude of immune response and poor pharmacokinetics. Herein we demonstrate a composite microsphere formulation, composed of mesoporous silica spheres (MPS) and poly(d,l-lactide-co-glycolide) (PLGA), enables the controlled delivery of a prime-boost vaccine via the encapsulation of plasmid DNA (pDNA) and protein in different compartments. Method with modified dual-concentric-feeding needles attached to a 40 kHz ultrasonic atomizer was studied. These needles focus the flow of two different solutions, which passed through the ultrasonic atomizer. The process synthesis parameters, which are important to the scale-up of composite microspheres, were also studied. These parameters include polymer concentration, feed flowrate, and volumetric ratio of polymer and pDNA-PEI/MPS-BSA. This fabrication technique produced composite microspheres with mean D[4,3] ranging from 6 to 34 µm, depending upon the microsphere preparation. The resultant physical morphology of composite microspheres was largely influenced by the volumetric ratio of pDNA-PEI/MPS-BSA to polymer, and this was due to the precipitation of MPS at the surface of the microspheres. The encapsulation efficiencies were predominantly in the range of 93-98% for pDNA and 46-68% for MPS. In the in vitro studies, the pDNA and protein showed different release kinetics in a 40 day time frame. The dual-concentric-feeding in ultrasonic atomization was shown to have excellent reproducibility. It was concluded that this fabrication technique is an effective method to prepare formulations containing a heterologous prime-boost vaccine in a single delivery system. © 2010 Elsevier B.V. All rights reserved. 2010 Journal Article http://hdl.handle.net/20.500.11937/17451 10.1016/j.ejps.2010.01.011 Elsevier Science restricted |
| spellingShingle | Ho, J. Huang, Y. Danquah, Michael Wang, H. Forde, G. Synthesis of biodegradable polymer-mesoporous silica composite microspheres for DNA prime-protein boost vaccination |
| title | Synthesis of biodegradable polymer-mesoporous silica composite microspheres for DNA prime-protein boost vaccination |
| title_full | Synthesis of biodegradable polymer-mesoporous silica composite microspheres for DNA prime-protein boost vaccination |
| title_fullStr | Synthesis of biodegradable polymer-mesoporous silica composite microspheres for DNA prime-protein boost vaccination |
| title_full_unstemmed | Synthesis of biodegradable polymer-mesoporous silica composite microspheres for DNA prime-protein boost vaccination |
| title_short | Synthesis of biodegradable polymer-mesoporous silica composite microspheres for DNA prime-protein boost vaccination |
| title_sort | synthesis of biodegradable polymer-mesoporous silica composite microspheres for dna prime-protein boost vaccination |
| url | http://hdl.handle.net/20.500.11937/17451 |