Development and production of polymer-based nanoparticles for use in the oral cavityBenčina, Lea (Avtor)
Gašperlin, Mirjana (Mentor)
Hiorth, Marianne (Komentor)
NanoparticlesIonic crosslinkingPolysaccharidesXerostomiaRheological synergismMucinMucoadhesionXerostomia, also known as “dry mouth,” is a common disease with reduced salivary flow. Due to the reduced protection functions of saliva, patients with xerostomia often have increased risk of oral diseases. Saliva substitutes available on the market have a short residence time in the oral cavity and therefore their effect is only temporary. There is a need to develop a product with prolonged residence time due to mucoadhesion, in the oral cavity, to provide prolonged relief from dry mouth. The overall aim of this thesis was to develop and produce polymer-based nanoparticles (NPs) for potential use in the treatment of xerostomia.
The polysaccharides used in the thesis were negatively charged alginate and low-methoxylated pectin (LM-pectin) and positively charged chitosan. NPs were prepared by ionic crosslinking. The NPs were characterized one day after preparation according to their size, polydispersity index (PDI), zeta potential (ZP) and turbidity. Furthermore, the long term stability of the NPs was measured. Some criteria were set and had to be achieved to consider the NPs as appropriate: The size of the NPs should be 100 – 500 nm; the PDI should be below 0,3; the absolute value of ZP should be larger than 30 mV and the samples should contain no visible aggregates (turbidity close to 0 cm-1). A rheological method was successfully set up and used for investigating the interaction between the polymers and mucin or the NPs and mucin. In order to modify the viscosity of the nanoparticle formulation to behave similar to human saliva, the neutral polymer hydroxethylcellulose (HEC) was added to the nanoparticle dispersions.
The most promising formulations were 0,05% w/w alginate NPs with the ZnCl2 to alginate ratio 35:65 and 0,05% chitosan NPs with the tripolyphosphate to chitosan ratio 15:85 or 20:80. Alginate and chitosan NPs remained stable over a period of one month, whereas LM-pectin NPs did not meet the criteria that was set. Negative rheological synergism was observed between chitosan and mucin, whereas the interaction between alginate or LM-pectin and mucin was not verified. The most promising interaction was observed between chitosan NPs (up-concentrated) and mucin. Namely, negative rheological synergism was calculated and a precipitation was observed with the naked eye. Alginate NPs also showed negative rheological synergism. It was impossible to verify a potential interaction between LM-pectin NPs and mucin probably due to the aggregation of the NPs already after up-concentration. It was possible to adjust the viscosity of the chitosan and alginate nanoparticle dispersions with HEC. Final viscosity values of the NPs mixed with HEC (1% w/w or 1,5% w/w) ranged from 2 mPas to 5 mPas, which was in accordance with the reported viscosity value of the whole human saliva (2 mPas to 10 mPas).20192019-06-28 09:28:47Magistrsko delo/naloga108334VisID: 67285sl