PH/TEMPERATURE-SENSITIVE POLYMERS FOR MACROMOLECULAR DRUG LOADING AND RELEASE

Beads formed from linear pH/temperature-sensitive polymers, poly (N-isopropylacrylamide-co-butylmethacrylate-co-acrylic acid), were evaluated as a potential polypeptide drug carrier in terms of loading efficiency, pH-dependent release, and preservation of bioactivity of loaded drugs. The beads were formed by precipitation of the polymers at the interface of cold aqueous solution droplets and warm oil phase, and subsequent drying process. The critial step in this bead formation and aqueous drug loading was found to be the initial formation of the skin layer, which was influenced by the oil bath temperature. The polypeptide drug loading efficiency was significantly increased by adjusting the ionic strength of the aqueous polymer/drug solution. The release rate of insulin at pH 7.4 and 37 degrees C was controlled by the acrylic acid content of the terpolymers, while minimal swelling and release were observed at pH 2.0 and 37 degrees C, regardless of the acrylic acid content. The bioactivities of insulin released from the beads at pH 7.4 and recovered from the beads which were kept in rat stomach for 5 h were well preserved. These results indicate that this polymeric system has a potential as a polypeptide drug carrier, especially for oral delivery.