A water-in-oil-in-oil-in-water (W/O/O/W) method for producing drug-releasing, double-walled microspheres

A water-in-oil-in-oil-in-water (W/O/O/W) method was developed to fabricate double-walled microspheres for controlled delivery of drugs and therapeutic proteins with reduced initial burst and prolonged release. By using this method, drugs and therapeutic proteins can be loaded into microspheres in solution form as those used in medical treatments. Proteins can be loaded in solutions together with excipients, thereby reducing the risk of losing stability in the process of protein drying and dispersing. This also benefits uniform distribution of drugs inside polymer matrix in comparison to the case with solid drug particles. These microspheres were characterized to have double-walled structure, with a cavity in the centre. The hydrophilic drugs were encapsulated in the inner polymer layer, while the non-drug-loaded outer layer served as a rate-limiting barrier. Drug release profiles for 5-fluorouracil showed low initial burst and prolonged release, which is substantiated by degradation studies.