Development and Evaluation of Acoustically Active Microbubbles as Drug Targeting Systems by in vitro and in vivo Models

The aim of this proposal is to develop and evaluate the microbubble systems for encapsulating anticancer drug as an injectable formulation. We had previously applied a proposal with a study duration for 3 years. However, the final decision by the reviewers is a preliminary 1 year duration. During the past few months, we have examined the targeting properties of the microbubbles and achieve a successful results. The stability test and drug delivery ability also indicate a good result. Hence we think a continuous investigation to the antitumoral drugs-loaded microbubbles is promised. 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. Besides camptothecin, irinotecan will be used as a model drug in this study to compare the experimental results of both antitumoral drugs. The experiments which will be performed in this two-year proposal are: 1. The first 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 second 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:PC9807-0305
External Project ID:NSC98-2320-B255-003-MY2