Process considerations related to the microencapsulation of plasmid DNA via ultrasonic atomization

Ho, Jenny, Wang, Huanting, & Forde, Gareth M. (2008) Process considerations related to the microencapsulation of plasmid DNA via ultrasonic atomization. Biotechnology and Bioengineering, 101(1), pp. 172-181.

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An effective means of facilitating DNA vaccine delivery to antigen presenting cells is through biodegradable microspheres. Microspheres offer distinct advantages over other delivery technologies by providing release of DNA vaccine in its bioactive form in a controlled fashion. In this study, biodegradable poly(D,L-lactide-coglycolide) (PLGA) microspheres containing polyethylenimine (PEI) condensed plasmid DNA (pDNA) were prepared using a 40 kHz ultrasonic atomization system. Process synthesis parameters, which are important to the scale-up of microspheres that are suitable for nasal delivery (i.e., less than 20 μm), were studied. These parameters include polymer concentration; feed flowrate; volumetric ratio of polymer and pDNA-PEI (plasmid DNA-polyethylenimine) complexes; and nitrogen to phosphorous (N/P) ratio. PDNA encapsulation efficiencies were predominantly in the range 82-96%, and the mean sizes of the particle were between 6 and 15 μm. The ultrasonic synthesis method was shown to have excellent reproducibility. PEI affected morphology of the microspheres, as it induced the formation of porous particles that accelerate the release rate of pDNA. The PLGA microspheres displayed an in vitro release of pDNA of 95-99% within 30 days and demonstrated zero order release kinetics without an initial spike of pDNA. Agarose electrophoresis confirmed conservation of the supercoiled form of pDNA throughout the synthesis and in vitro release stages. It was concluded that ultrasonic atomization is an efficient technique to overcome the key obstacles in scaling-up the manufacture of encapsulated vaccine for clinical trials and ultimately, commercial applications.

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12 citations in Web of Science®

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ID Code: 81545
Item Type: Journal Article
Refereed: Yes
Keywords: Microspheres, Plasmid DNA, Poly(D, L-lactide-co- glycolide), Polyethylenimine, Ultrasonic atomization, Atomization, Chlorine compounds, Complexation, Concentration (process), Controlled drug delivery, DNA, Electrophoresis, Encapsulation, Fluid mechanics, Genes, Hydraulics, Jets, Nitrogen, Nonmetals, Nucleic acids, Organic acids, Phosphorus, Polymers, Spraying, Ultrasonic applications, Ultrasonic testing, Ultrasonics, Vaccines, Agarose, Antigen-presenting cells, Clinical trials, Commercial applications, D, L-lactide, DNA vaccines, Flow-rate, In vitro releases, Nasal delivery, PLGA microspheres, Polymer concentrations, Porous particles, Process synthesis, Release rates, Reproducibility, Scale-up, Scaling-up, Supercoiled, Ultrasonic atomizations, Ultrasonic synthesis, Volumetric ratios, Zero order release, DNA vaccine, microsphere, polyethyleneimine, polyglactin, agar gel electrophoresis, article, drug delivery system, drug synthesis, mathematical computing, microencapsulation, nebulization, particle size, Capsules, Diffusion, Drug Carriers, Drug Compounding, Kinetics, Lactic Acid, Plasmids, Polyglycolic Acid, Sonication
DOI: 10.1002/bit.21876
ISSN: 0006-3592
Divisions: Current > Schools > School of Chemistry, Physics & Mechanical Engineering
Current > QUT Faculties and Divisions > Science & Engineering Faculty
Deposited On: 05 Feb 2015 23:28
Last Modified: 11 Feb 2015 03:34

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