Abstract: Objective To study the effect of low frequency on drug release from improved PLGA microcapsules, and investigate the possibility of utilizing PLGA microcapsules as the carrier of ultrasound targeted drug delivery system to deliver drug into brain. Methods Doxorubicin loaded poly (D,L lactic-co-glycolic acid) (PLGA) microcapsules were prepared via double emulsion solvent evaporate method and coated with either chitosan or gelatin. In vitro drug release profile and the drug release rate under the exposure of low frequency pulsed ultrasound (25 kHz) and continuous wave ultrasound (35.1 kHz) were assayed. Results The coating with chitosan or gelatin can depress the burst of drug release. The drug release rate from uncoated and chitosan-coated microcapsules did not changed with the exposure of ultrasound, and the rate of gelatin-coated microcapsules did increased. The effect of pulsed ultrasound was stronger than that of continuous ultrasound. Conclusion The drug release from gelatin-coated PLGA microcapsules can be controlled and triggered by 25 kHz pulsed ultrasound, which may be a potent carrier of targeting drugs into brain.

Key words: low frequency ultrasound, drug delivery, doxorubicin, polymer, poly (D, L lactic-co-glycolic acid) (PLGA), microcapsule, gelatin, chitosan