The incorporation of poorly soluble drugs into nanofibres by electrospinning from carboxylic acid polymer solutions

Shabangu, Dumisani (2017-12)

Thesis (MSc)--Stellenbosch University, 2017.

Thesis

ENGLISH ABSTRACT: Carboxylic acids were used to generate electrospun fibres of polycaprolactone (PCL) via a free surface electrospinning methodology for the first time. The electrospinnability of the polymer solutions was dependent on the conductivity of the polymer solutions, which is related to the carboxylic acid’s pKa. The pKa influenced the dissolution ability of the carboxylic acid. Furthermore, the carboxylic acid type influences the solution properties. Carboxylic acids with a lower value of the pKa lead to lower observed solution viscosity. Needle electrospinning results show that carboxylic acid type influences the occurrence of critical chain entanglements. Additionally, salt additives can be used to enable needle electrospinning in low conductivity carboxylic acid polymer solutions. Carboxylic acid type influences the average fibre diameter of electrospun PCL. Polymer solutions with a comparatively higher value of conductivity lead to thicker fibres. PCL polymer solution properties evolve with time, more specifically viscosity. The viscosity decreases with an increase in solution age. The decrease in polymer solution viscosity is accompanied by a decrease in average fibre diameter. Furthermore, the decrease in viscosity and average fibre diameter is accompanied by a decrease in polymer molecular weight. The polymer processing type influences the crystallinity of the polymer. More specifically, fibres show a larger crystallinity compared to films generated from the same solvent system. Free surface electrospinning leads to an inconsistent crystal size distribution. Stable oil-in-acid emulsions were successfully formed. The dispersed phase type influences the emulsion stability. The continuous phase type influences the emulsion electrospinning as it makes up the bulk of the solution. The surfactant type influences emulsion electrospinning, with cationic surfactants leading to thinner fibres when positive potential is applied. Emulsion electrospinning leads to the encapsulation of the dispersed phase components. This led to the successful incorporation of a hydrophobic, poorly soluble drug in electrospun fibres. The internal fibre morphology is an islands-at-sea type morphology. Sustained release of curcumin in a phosphate buffer proved unsuccessful. Burst release was obtained by solution modification which was obtained by surfactant addition. The difficulty in obtaining sustained release of curcumin may be related in the difficulty of wetting the electrospun fibres.

AFRIKAANSE OPSOMMING: Karboksielsure was gebruik om elektrospin vesels van polikaprolaktoon (PKL) te produseer deur, vir die eerste keer, gebruik tee maak van ‘n vrye oppervlak elektrospin metode. Die elektrospin van die polimeeroplossings is afhanklik van die geleiding daarvan wat verwant is aan die karboksielsure se pKa waarde aangesien die pKa die ontbindingsvermoë van die karboksielsuur beïnvloed. Die tipe karboksielsuur speel ‘n rol in die eienskappe van die oplossing. Karboksielsure met ‘n lae pKa waarde lei tot oplossings met waarneembare laer viskositeit. Naald elektrospin resultate wys dat die tipe karboksielsuur die voorkoms van kettingverstrengelings beïnvloed. In die geval van oplossings met swak geleidingsvermoëns kan sout bygevoeg word om die elektrospin daarvan moontlik te maak. Die tipe karboksielsuur het ook ‘n invloed op die deursnee van die PKL vesels. Polimeeroplossings met goeie geleidingsvermoëns het gelei tot dikker vesels. Daar is ook waargeneem dat die eienskappe van die PKL oplossings verander het oor tyd. Meer spesifiek, die viskositeit het gedaal het met die verloop van tyd. Die afname in die viskositeit van die oplossings het gepaard gegaan met ‘n afname in die deursnee van die vesels en die molekulêre gewig van die polimeer. Die verwerkingsmetode van ‘n polimeer bepaal ondermeer die kristalliniteit daarvan. Polimeervesels byvoorbeeld, het ‘n hoër kristalliniteit as films wat geprodusser is van dieselfde oplosmiddelsisteem. Vrye oppervlak elektrospin lei tot ‘n strydige verspreiding van kristal grootte. Stabiele olie-in-suur emulsies was susksesvol voorberei. Die tipe verspreide fase beïnvloed die stabiliteit van die emulsie. Die deurlopende fase beïnvloed op sy beurt die elektrospin proses van die emulsie, aangesien dit die meerderheid van die oplossing opmaak. Die tipe benattingsmiddel het ook ‘n invloed op die elektrospin proses van ‘n emulsie deurdat ‘n kationiese benattingsmiddel lei tot dunner vesels met die toepassing van positiewe potensiaal. Die elektrospin van ‘n emulsie lei to die inkapseling van die komponente van die dispersie fase wat nodig is vir die suksesvolle inkorporasie van die hidrofobiese dwelmmiddel in die polimeervesels. Die interne morfologie van hierdie vesels was die eiland-by-die-see tipe. Die volgehoue vrylating van die curcumin in ‘n fosfaatbuffer was onsuksesvol. Bars vrylating was waargeneem na die aanpassing van die oplossing deur die byvoeging van ‘n benattingsmiddel. Die moeilikheid om die volgehoue vrylating van die curcurim te verkry kan moontlik verwant wees aan die moeilikhied om die vesels te benat.

Please refer to this item in SUNScholar by using the following persistent URL: http://hdl.handle.net/10019.1/102643
This item appears in the following collections: