Synthesis of biodegradable polymer–mesoporous silica composite microspheres for DNA prime-protein boost vaccination
| Autor: | Gareth M. Forde, Yi Huang, Michael K. Danquah, Huanting Wang, Jenny Ho |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
chemistry.chemical_classification
Materials science Heterologous vaccine Polymers Silicon dioxide Drug Compounding Composite number Pharmaceutical Science Serum Albumin Bovine Nanotechnology Polymer Mesoporous silica Silicon Dioxide Biodegradable polymer Microspheres chemistry.chemical_compound PLGA chemistry Chemical engineering Microscopy Electron Scanning Vaccines DNA Particle Size Microparticle Plasmids |
| Zdroj: | European Journal of Pharmaceutical Sciences. 39:412-420 |
| ISSN: | 0928-0987 |
| DOI: | 10.1016/j.ejps.2010.01.011 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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