Synthesis of biodegradable polymer-mesoporous silica composite microspheres for DNA prime-protein boost vaccination

Ho, Jenny, Huang, Yi, Danquah, Michael K., Wang, Huanting, & Forde, Gareth M. (2010) Synthesis of biodegradable polymer-mesoporous silica composite microspheres for DNA prime-protein boost vaccination. European Journal of Pharmaceutical Sciences, 39(5), pp. 412-420.

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Abstract

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.

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13 citations in Web of Science®

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ID Code: 81533
Item Type: Journal Article
Refereed: Yes
Keywords: Composite microspheres, Heterologous vaccine, Mesoporous silica spheres, Plasmid DNA, Protein boost, bovine serum albumin, DNA vaccine, enhanced green fluorescent protein, microsphere, polyethyleneimine, polyglactin, polymer, silicon dioxide, article, biodegradability, composite material, concentration (parameters), controlled study, DNA immunization, drug delivery system, drug formulation, drug release, drug synthesis, encapsulation, flow rate, in vitro study, particle size, porosity, precipitation, priority journal, reproducibility, scale up, structure analysis, volumetry, Drug Compounding, Microscopy, Electron, Scanning, Microspheres, Plasmids, Polymers, Serum Albumin, Bovine, Vaccines, DNA
DOI: 10.1016/j.ejps.2010.01.011
ISSN: 0928-0987
Divisions: Current > Schools > School of Chemistry, Physics & Mechanical Engineering
Current > QUT Faculties and Divisions > Science & Engineering Faculty
Deposited On: 05 Feb 2015 23:10
Last Modified: 11 Feb 2015 02:04

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