Jakobsen, Petrus

Abstract

A challenge facing the medical sector is the treatment of non-healing chronic wounds and the threat of multidrug resistant bacteria strains. A potential solution to these challenges would be to create wound care bandages with better durability and reduced risk of cultivating multidrug resistant bacteria strains. In this thesis, a solution is proposed by incorporatin biocompatible polymer microspheres containing the antiseptic agents octenidine dihydrochloride (OCT) and benzalkonium chloride (BAC) in a nonwoven cellulose material. The spheres were formulated using the solvent evaporation method, where the influence of emulsifier and homogenization on the sphere stability and size were investigated. It was found that a higher concentration of emulsifier counteracted aggregation of the spheres and that stirring for a short time gave the largest spheres. The mainly used polymers were poly(lacticco-glycolic acid) (PLGA), poly(L-lactic acid) (PLLA) and bis–(2–carboxyphenyl) adipate polyanhydride (SASanhydride). The influence of the active substance on the interfacial tension was investigated with optical tensiometry by measuring the interfacial tension of dichloromethane(DCM) droplets with different concentrations of active substance to a water phase. Both OCT and BAC are surface active agents and had a considerable effect on the interfacial tension between the DCM droplets and the surrounding aqueous medium. The reduced interfacial tension due to the surface activity of BAC and in particular OCT resulted in smaller spheres. The formulated microspheres with OCT were subsequently incorporated into a nonwoven fiber material using solution-blow spinning. In this process, a solution was created containing an ionic liquid and microcrystalline cellulose where the spheres containing the active substance were dispersed. The ionic liquid, in this case, 1- ethyl-3-methylimidazolium acetate(EmimAc) was used to dissolve the cellulose. To determine the amount of active substance required in the nonwoven fiber to achieve an antimicrobial effect, the minimal inhibitory concentration (MIC) was used. At MIC the bacteria population in the wound is contained. With the proposed fabrication process, the incorporated amount of BAC in the fiber is assumed to lead to a concentration below the MIC while the concentration may be high enough for fibers with OCT containing spheres. To increase the BAC content in the fiber, a possible solution could be impregnation with BAC combined with microspheres containing BAC. A distribution coefficient, KOCT = 6.23 and KBAC = 2.86 for the active substances was determined with respect to the distribution between the polymer and water phase. The result indicated that there was a risk of leakage of active substance from the polymer spheres to the water phases in the emulsion and particularly in the coagulation and wash bath used in the solution-blow spinning. Solubility tests for OCT were done where it was found to have a higher solubility then values found in the literature.

Keywords

PLGA ; PLLA ; SASanhydride ; microspheres ; solution-blow spinning ; solvent evaporation ; emulsion ; interfacial tension ; distribution coefficient ; octenidine dihydrochloride ; benzalkonium chloride

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