Preparation and characterisation of biodegradable microspheres for the delivery of bioactive compounds

Sammanfattning: The incorporation of bioactive compounds into biodegradable polymer microspheres has several advantages. Firstly, the drug substance is protected from physiological degradation. Secondly, using microspheres from polymers with different degradation mechanisms, it is possible to design different release profiles with desired release rates. Thirdly, patient compliance and comfort may be improved because frequent dosing can be avoided.Emulsion techniques for incorporation of drugs into biodegradable microspheres intended for controlled release have been optimised in this thesis. Various types of microspheres are characterised and evaluated as drug carriers in an ocular delivery system and for the oral delivery of vaccines. Emulsion solvent evaporation techniques were used for the preparation of microspheres from the polymers poly(lactide-co-glycolide) (PLG) and poly(adipic anhydride) (PAA). The processing parameters were adjusted to optimise properties such as the size, the degree of drug-loading and the retention of bioactivity of incorporated proteins. The size of the prepared microspheres was controlled by the emulsification process and by the concentration of polymer. The use of ethyl acetate instead of methylene chloride and the co-incorporation of gelling poloxamer increased the retained enzymatic activity of incorporated urease.A new ocular drug delivery system was developed. This system is based on drug incorporated into PAA microspheres dispersed in an in situ gel. This system is intended to extend the duration of precorneal contact as compared with ordinary eye drops. Incorporated timolol maleate was released from the microsphercs at a constant rate over 7 h. The degradation of PAA was the rate-limiting step in the release of drug. The concept of using a microsphere-gel formulation may result in improved ocular bioavailability of drugs, particularly those that are water soluble.Inactivated rotavirus was incorporated into both PLG microspheres and poly(acrylic starch) (PAS) microspheres; these were administered orally or intramuscularly to mice. The immune responses induced by the two polymer adjuvant systems were dependent on the route of administration and on the different mechanisms for antigen release and degradation of the polymers. The immune response after oral administration was higher for PAS than for PLG.