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Potential for Scaled-up Manufacture of Chitosan Nanoparticles Using the Spinning Disc Processor

J. W. Loh1, M. Saunders3 & L. Y. Lim1,2

1Laboratory for Drug Delivery, 2Centre for Strategic Nano-fabrication (Incorporating Toxicology), School of Biomedical, Biomolecular and Chemical Sciences, 3Centre for Microscopy, Characterisation and Analysis, The University of Western Australia, Crawley, WA, 6009, Australia, (Email: Loh, lohj05@student.uwa.edu.au; Saunders, martin.saunders@uwa.edu.au; Lim, limly@cyllene.uwa.edu.au)

ABSTRACT

Spinning disc processing (SDP) is an innovative and robust continuous flow technology that has great potential for the scaled up production of nanoparticles. This study examined the feasibility of producing chitosan nanoparticles by SDP technology. Analysis by dynamic light scattering suggested that chitosan nanoparticles produced by SDP (19.6 ± 2.8 nm diameter, n = 4) were similar in size compared to those produced by the conventional ionotropic gelation method (30.6 ± 12.5 nm, n = 3), while laser Doppler anemometry detected significant differences (p < 0.05) in the zeta-potential of the nanoparticles (SDP: 53.3 ± 4.3 mV, n = 3; conventional: 38.7 ± 6.1 mV, n = 3). The SDP-manufactured chitosan nanoparticles were spherical and discrete when viewed under the transmission electron microscope. In summary, SDP technology can be a reliable method for the commercial production of chitosan nanoparticles of a consistent quality

Keywords: chitosan nanoparticles, spinning disc processing 1 INTRODUCTION

Chitosan has been widely investigated for biomedical applications because of its biocompatibility, biodegradability, and mucoadhesive properties [1]. This polymer has been employed in drug and gene delivery[2], wound dressings [3] and tissue engineering [4]. In recent years, nanoparticles of chitosan have also been synthesized to impart increased reactivity and biological activity, particularly in the fields of drug and gene delivery [5, 6]. Currently, chitosan nanoparticles are manufactured by many laboratories using batch processing methods, some of which utilize toxic chemicals and harsh processing conditions [7], are limited in production capacity and present the operator with little control over the characteristics of the nanoparticles. To realize the commercial potential of chitosan nanoparticles, a large scale production method must be available that will yield a product of acceptable quality to the regulatory authorities. The production method must also be cost effective, flexible and readily validated.

The aim of this study was to investigate the potential of the spinning disc processing (SDP) technology for scaled up production of chitosan nanoparticles. SDP uses a small equipment for continuous flow processing. Reactants are introduced on a rotating disc where they are mixed under controlled conditions to produce nanoparticles of requisite size (Figure 1). It is simple to operate, and is readily adapted to bulk manufacturing without necessarily increasing the size of the processor. The manufacturing process may be controlled by optimizing the feed rates of reactants, along with the temperature and speed of mixing on the spinning disc. The SDP has been shown to be a reliable and efficient method for fabricating nanoparticles under 10 nm, with remarkable control over the size, shape and agglomeration of the nanoparticles [8-10]. The continuous flow technology further eliminates batch-to- batch variations in the nanoparticle production.

Figure 1: Schematic Diagram of the Spinning Disc Processor [10]

A wide variety of inorganic nanoparticles, including: metal coated carbon nanotubes [11], mesoporous silica capsules [12] and zinc oxide nanoparticles [13], has been successfully produced using the SDP. There is however, considerably less experience in using the SDP to manufacture organic nanoparticles. To assess the SDP method for scaled up production, chitosan nanoparticles produced using the SDP were compared to those synthesized using conventional batch processing methods based on ionotropic gelation of chitosan with the

NSTI-Nanotech 2008, www.nsti.org, ISBN 978-1-4200-8504-4 Vol. 2 669

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 Supercritical Fluid Extraction 242.pdf Page 001
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