Formulation and characterisation of polyelectrolyte complex nanoparticles for the delivery of salmon calcitonin
Citation:Anita Monika Umerska, 'Formulation and characterisation of polyelectrolyte complex nanoparticles for the delivery of salmon calcitonin', [thesis], Trinity College (Dublin, Ireland). School of Pharmacy & Pharmaceutical Sciences, 2013, pp 359
Umerska TCD THESIS 10003 Formulation and.pdf (PDF) 216.3Mb
The studies in this thesis explored the formulation of various polyelectrolyte complex nanoparticles as potential carriers for the delivery of macromolecules. The complexes were formed between a polyanion (hyaluroninc acid, HA or chondroitin, CHON) and a polycation (chitosan, CS, or protamine, PROT). Salmon calcitonin (sCT) was selected as a macromolecule to be encapsulated in the nanoparticles due to its clinical use in bone diseases and potential application in arthritis. Different factors influencing the formation and properties of the nanoparticles (NPs) were examined, e.g. concentration of the polymers, polyanion/polycation mixing ratio, molecular weight of polymers. The molecular weight of the polymers was determined by GPC (Gel Permeation Chromatography). The properties of the NPs were characterised with the use of different techniques. Particle size and size distribution were analysed with the employment of dynamic light scattering (DLS), zeta potential was measured with the use of laser Doppler velocimetry (LDV), while morphology was investigated by transmission electron microscopy (TEM) and scanning electron microscopy (SEM). Physical stability of the nanoparticle suspensions upon storage at room temperature were performed for a period up to 4 weeks. sCT was loaded into each type of NPs: HA/CS, CHON/CS, HA/PROT and CHON/PROT, and the possibility of formation of NPs between sCT and polyanionsiHA and CHON was also examined. Non-associated sCT was separated from NPs by a combined ultrafiltration-centrifugation technique, and concentration of sCT was analysed by HPLC (high performance liquid chromatography). The release of sCT from the polyelectrolyte complex nanoparticles was also examined. Selected formulations were converted into solid state forms by freeze-drying with the employment of trehalose and poly(ethylene glycol) polymers (PEGs) as cryoprotectants. The toxicity of the NPs, polymers and cryoprotectants was examined on Caco-2 cells with the use of MTS assay and flow cytometry. The in vitro (cell culture) and in vivo (in rats) performance of HA/CS/sCT NPs was also examined. Uncomplicated, organic solvent and surfactant-free production method by simply mixing aqueous solutions of polylelctrolytes at room temperature was successfully employed to fabricate novel, cross-linker-free and non-sedimenting nanoparticles.
Author: Umerska, Anita Monika
Corrigan, Owen I.
Publisher:Trinity College (Dublin, Ireland). School of Pharmacy & Pharmaceutical Sciences
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Type of material:thesis
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