Effects of polymer, organic solvent and mixing strength on integrity of proteins and liposomes encapsulated in polymeric microspheres fabricated by the double emulsion process

The double emulsion process has commonly been applied to encapsulate water-soluble bioactive agents into polymeric microspheres. However, the integrity of many of these agents may be destroyed by the highly energetic procedures such as sonication that are routinely used to produce stable water-in-oil (w/o) emulsion. The aim of this research was to pursue the possibility of replacing the sonication by a mild emulsification procedure such as vortex mixing, with the use of certain materials to help to obtain stable w/o emulsion. The following materials were examined: poly(lactide-co-ethylene glycol) (PELA) as the polymer, ethyl acetate and acetone as the solvents, poly(vinyl alcohol) (PVA) and d-α tocopheryl polyethylene glycol 1000 succinate (Vitamin E TPGS) as the emulsifiers in w/o emulsion. The experimental results, with human serum albumin (HSA) as the encapsulated agent, showed that, when vortex mixing was used, these materials could significantly improve w/o emulsion stability and help to obtain satisfactory encapsulation effects, i.e. high encapsulation efficiency (EE) and low initial release burst. A delicate structure, i.e. liposomes, which is very sensitive to sonication, was then incorporated into microspheres by the 'modified double emulsion process'. It was found that the liposomes were intact and the encapsulation effects were good. Therefore, it can be concluded that the modified double emulsion process could be advantageous for the encapsulation of delicate substances.