title: Synthesis of biodegradable polymer-mesoporous silica composite microspheres for DNA prime-protein boost vaccination.
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 microm, 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.
authors.affiliation: Department of Chemical Engineering, Monash University, Clayton 3800, VIC, Australia. jenny.ho@eng.monash.edu.au
authors.forename: Jenny
authors.initials: J
authors.lastname: Ho
authors.forename: Yi
authors.initials: Y
authors.lastname: Huang
authors.forename: Michael K
authors.initials: MK
authors.lastname: Danquah
authors.forename: Huanting
authors.initials: H
authors.lastname: Wang
authors.forename: Gareth M
authors.initials: GM
authors.lastname: Forde
mesh_terms: D004339:Drug Compounding; D008855:Microscopy, Electron, Scanning; D008863:Microspheres; D010316:Particle Size; D010957:Plasmids; D011108:Polymers / Q000138:chemical synthesis*; D012710:Serum Albumin, Bovine / Q000008:administration & dosage*; D012822:Silicon Dioxide / Q000138:chemical synthesis*; D019444:Vaccines, DNA / Q000008:administration & dosage*
chemical_list: D011108:Polymers; D019444:Vaccines, DNA; D012710:Serum Albumin, Bovine; D012822:Silicon Dioxide