Design and Development of Acoustically Active Microbubbles as Drug Targeting Systems

The aim of this proposal is to develop and evaluate the microbubble systems for encapsulating anticancer drug as an injectable formulation. Microbubbles can remain in body for a longer duration and attain a drug targeting effect. Microbubbles were used as contrast agents for clinical diagnosis in the earlier time. The microbubbles are spherical structures full with perfluorocarbon gas in the internal cores. Recently, this system is injected into the body with the assistance of ultrasound to effectively transfer the drug to the nidus. Camptothecin is an anticancer drug with wide application. Because of the high toxicity on normal tissues and insolubility in water, camptothecin is always used by chemical modification in the clinical situation. However, camptothecin always shows a higher potency than its derivatives. Moreover, the semi-synthesis of camptothecin is high cost and time consuming. Hence lipid-coated microbubbles may be suitable to encapsulate camptothecin to solve these problems and achieve drug targeting effect. The experiments which will be performed in this three-year proposal are: 1. The first year: To evaluate the feasibility and possibility of lipid-coated microbubbles for delivering the anticancer drug. The basically physicochemical characteristics of the microbubbles will be determined. 2. The second year: To evaluate the in vitro release characteristics of camptothecin from microbubbles with or without ultrasound application. The cancer cell viability is also evaluated by treating camptothecin-loaded microbubbles. 3. The third year: To evaluate the in vivo animal study. Both the pharmacokinetic and pharmacodynamic experiments will be performed to confirm the ability of microbubbles for sustain and prolong drug release and duration. We wish to develop the acoustically active microbubbles incorporated with oil and perfluorocarbon for entrap camptothecin. The formulation design includes variables of gas types and emulsifier types. The application of ultrasound may target the drug to the tumor in order to maximize therapeutic activity and minimize the adverse drug reaction.

Project ID:PC9709-0203
External Project ID:NSC97-2320-B182-003