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

Jenny Ho*, Yi Huang, Michael K. Danquah, Huanting Wang, Gareth M. Forde

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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 mu m, 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. (C) 2010 Elsevier B.V. All rights reserved.

Original languageEnglish
Pages (from-to)412-420
Number of pages9
JournalEuropean Journal of Pharmaceutical Sciences
Volume39
Issue number5
DOIs
Publication statusPublished - 18 Mar 2010
Externally publishedYes

Keywords

  • Mesoporous silica spheres
  • Composite microspheres
  • Plasmid DNA
  • Protein boost
  • Heterologous vaccine
  • NONVIRAL GENE DELIVERY
  • ULTRASONIC ATOMIZATION
  • PLASMID DNA
  • POLY(LACTIDE-CO-GLYCOLIDE) MICROSPHERES
  • CURRENT PROGRESS
  • IN-VITRO
  • VACCINES
  • MICROENCAPSULATION
  • NANOPARTICLES
  • ENCAPSULATION

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