Effects of processing parameters on particle size of ultrasound prepared chitosan nanoparticles: an Artificial Neural Networks Study.
ABSTRACT The pharmacokinetic properties of chitosan nanoparticles have been shown to mainly depend on its particle size. The aim of this study was to concurrently evaluate and model the effective parameters, namely, chitosan concentration, buffer pH, amplitude and time of sonication, on the particle size of chitosan nanoparticles. Chitosan solutions were prepared and sonicated with different values for the above mentioned parameters. The data were then modeled using artificial neural networks (ANNs). The results illustrated that all four input parameters affect the size of prepared chitosan nanoparticles. While a reverse effect was observed between the size and the buffer pH as well as time and amplitude of sonication, the concentration was found to directly influence the particle size. The optimum condition to obtain the minimum size of nanoparticles in the range of 50-200 nm was found to be high values of pH and sonication time (i.e. approximately 4.9 and 500 s, respectively) and amplitude values of more than ~55.
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ABSTRACT: Sustained, local delivery of immunomodulatory cytokines is under investigation for its ability to enhance vaccine and anti-tumor responses both clinically and preclinically. This study evaluates the ability of chitosan, a biocompatible polysaccharide, to (1) control the dissemination of a cytokine, GM-CSF, and (2) enhance the immunoadjuvant properties of GM-CSF. While cytokines have previously been delivered in lipid-based adjuvants and other vehicles, these do not have the clinical safety profile or unique properties of chitosan. We found that chitosan solution maintained a measurable depot of recombinant GM-CSF (rGM-CSF) at a subcutaneous injection site for up to 9 days. In contrast, when delivered in a saline vehicle, rGM-CSF was undetectable in 12-24h. Furthermore, a single s.c. injection of 20 microg rGM-CSF in chitosan solution (chitosan/rGM-CSF(20 microg)) transiently expanded lymph nodes up to 4.6-fold and increased the number of MHC class II expressing cells and dendritic cells by 7.4-fold and 6.8-fold, respectively. These increases were significantly greater than those measured when rGM-CSF was administered in saline at the standard preclinical dose and schedule, i.e. 4 daily s.c. injections of 20 microg. Furthermore, lymph node cells from mice injected with chitosan/rGM-CSF(20 microg) induced greater allogeneic T cell proliferation, indicating enhanced antigen presenting capability, than lymph node cells from mice injected with rGM-CSF alone. Finally, in vaccination experiments, chitosan/rGM-CSF was superior to either chitosan or rGM-CSF alone in enhancing the induction of antigen-specific CD4(+) proliferation, peptide-specific CD8(+) pentamer staining and cytotoxic T cell lysis. Altogether, chitosan/rGM-CSF outperformed standard rGM-CSF administrations in dendritic cell recruitment, antigen presentation and vaccine enhancement. We conclude that chitosan solution is a promising delivery platform for the sustained, local delivery of rGM-CSF.Vaccine 01/2008; 25(52):8673-86. · 3.49 Impact Factor
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ABSTRACT: This work investigates the polyanion initiated gelation process in fabricating chitosan-TPP (tripolyphosphate) nanoparticles in the size range of 100-250 nm intended to be used as carriers for the delivery of gene or protein macromolecules. It demonstrates that ionic gelation of cationic chitosan molecules offers a flexible and easily controllable process for systematically and predictably manipulating particle size and surface charge which are important properties in determining gene transfection efficacy if the nanoparticles are used as non-viral vectors for gene delivery, or as delivery carriers for protein molecules. Variations in chitosan molecular weight, chitosan concentration, chitosan to TPP weight ratio and solution pH value were examined systematically for their effects on nanoparticle size, intensity of surface charge, and tendency of particle aggregation so as to enable speedy fabrication of chitosan nanoparticles with predetermined properties. The chitosan-TPP nanoparticles exhibited a high positive surface charge across a wide pH range, and the isoelectric point (IEP) of the nanoparticles was found to be at pH 9.0. Detailed imaging analysis of the particle morphology revealed that the nanoparticles possess typical shapes of polyhedrons (e.g., pentagon and hexagon), indicating a similar crystallisation mechanism during the particle formation and growth process. This study demonstrates that systematic design and modulation of the surface charge and particle size of chitosan-TPP nanoparticles can be readily achieved with the right control of critical processing parameters, especially the chitosan to TPP weight ratio.Colloids and surfaces B: Biointerfaces 09/2005; 44(2-3):65-73. · 3.55 Impact Factor
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ABSTRACT: The aim of this review is to give an insight into the many potential applications of chitosan as a pharmaceutical drug carrier. The first part of this review concerns the principal uses of chitosan as an excipient in oral formulations (particularly as a direct tableting agent) and as a vehicle for parenteral drug delivery devices. The use of chitosan to manufacture sustained-release systems deliverable by other routes (nasal, ophthalmic, transdermal, and implantable devices) is discussed in the second part.Drug Development and Industrial Pharmacy 12/1998; 24(11):979-93. · 1.54 Impact Factor