Chitosan microparticles for the controlled delivery of fluoride.
OBJECTIVE
To manufacture and characterise chitosan/fluoride microparticles prepared by spray drying and assess their utility as controlled release vehicles for fluoride.


METHODS
Microparticles were manufactured from dispersions containing 1.0% and 2.0% (w/v) chitosan and 0.20% or 0.40% (w/v) NaF in the absence/presence of glutaraldehyde. Particle size distributions were determined using laser diffraction; fluoride loading and release were determined by ion-selective electrode. Release profiles were studied in isotonic media (pH 5.5) over 360 min; microparticles exhibiting greatest cumulative fluoride release were further evaluated at pH 4.0 and 7.0. Particle morphology was investigated using environmental scanning electron microscopy. Bioadhesion parameters were determined with a texture-probe analyser.


RESULTS
Microparticles exhibited low polydispersity and volume mean diameters (VMDs) <6 μm. VMDs increased on doubling the chitosan/fluoride concentrations but were largely independent of glutaraldehyde concentration. Recovered yields were inversely proportional to dispersion viscosity due to compromised fluid atomisation; adding NaF reduced viscosity and improved yields. Best-case entrapment efficiency and NaF loading were 84.1% and 14%, respectively. Release profiles were biphasic, releasing 40-60% of the total fluoride during the first 600 s, followed by a prolonged release phase extending out to 6h. Incorporation of 0.40% NaF to the 2.0% chitosan dispersion yielded microparticles with reduced bioadhesive parameters (F(max) and WOA) versus the chitosan-only control whilst retaining significant bioadhesive potential.


CONCLUSIONS
Bioadhesive chitosan/fluoride microparticles manufactured using a spray-drying protocol have been extensively characterised and further opportunity for optimisation identified. These microparticles may provide a means of increasing fluoride uptake from oral care products to provide increased protection against caries, however further work is required to demonstrate this principle in vivo.


CONCLUSIONS
Spray-drying is a low-cost route for the manufacture of bioadhesive chitosan/fluoride microparticles which can be exploited as controlled fluoride release agents to aid fluoride retention in the oral cavity. The potential exists to optimise release profiles to suit the delivery format thereby maximising the cariostatic benefits.
Chiesi Ltd., Chippenham, Wiltshire SN14 0AB, UK.
Gemma M
GM
Keegan
John D
JD
Smart
Matthew J
MJ
Ingram
Lara-Marie
LM
Barnes
Gary R
GR
Burnett
Gareth D
GD
Rees
D000268:Adhesiveness; D000336:Aerosols; D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry*; D002327:Cariostatic Agents / Q000008:administration & dosage* / Q000737:chemistry; D048271:Chitosan / Q000737:chemistry*; D003432:Cross-Linking Reagents / Q000737:chemistry; D003692:Delayed-Action Preparations; D003890:Desiccation; D004058:Diffusion; D005976:Glutaral / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D017736:Ion-Selective Electrodes; D007552:Isotonic Solutions / Q000737:chemistry; D007834:Lasers; D008422:Materials Testing; D008855:Microscopy, Electron, Scanning; D009092:Mucous Membrane / Q000166:cytology; D010316:Particle Size; D012969:Sodium Fluoride / Q000008:administration & dosage* / Q000737:chemistry; D013499:Surface Properties; D013552:Swine; D013997:Time Factors; D046509:Tissue Culture Techniques; D014783:Viscosity
D000336:Aerosols; D001672:Biocompatible Materials; D002327:Cariostatic Agents; D003432:Cross-Linking Reagents; D003692:Delayed-Action Preparations; D007552:Isotonic Solutions; D012969:Sodium Fluoride; D048271:Chitosan; D005976:Glutaral