Over the past decades, drug delivery systems have been studied, various formulations was particulate carriers, hydrogel based on polymer, lipids etc. for supporting safe and effective treatment of different diseases. However, conventional drug delivery systems remained several problems such as quick initial release, cytotoxicity in vivo and cannot fulfill the needs of biomedical research. Therefore, advanced drug delivery strategy need to be maintained plasma therapeutic drug concentrations at therapeutic range for longer periods of time. In this study, a multi-drug delivery system carried to target site therapeutic drug using combinational injectable formulation in vivo, has been reported.
Chapter 1 describes general introduction about background of the research, overall drug delivery systems and combination therapy for cancer treatment.
Chapter 2 illustrates the preparation of multi-formulations using microcapsule and injectable hydrogels to achieve desired therapeutic range for over a specific period of time. Injectable multi-formulations were prepared by mixing BSA-FITC encapsulated PLGA microcapsules and chitosan, Pluronic®, or methoxy poly(ethylene glycol)-b-poly(3-caprolactone) (MPEG-b-PCL) hydrogel. All multi-formulations were prepared in solutions and formed a gel state after injection into a rat. Monitoring in vivo BSA-FITC release, demonstrated that the initial burst release of BSA-FITC was retarded by injectable hydrogels. In this study, the bioavailability of BSA-FITC from multi-formulations was found to depend on the viscosities of injectable hydrogels. Consequently, the viscosity of the injectable hydrogels was considered as an important factor influencing the initial burst and duration of BSA-FITC release.
Chapter 3 derails the combinational chemotherapy via intratumoral injection of doxorubicin (Dox) and 5-fluorouracil (Fu) using the developed combinational formulation of hydrogel and microcapsule in chapter 2., to enhance the efficacy and reduce the toxicity of systemically administered Fu and Dox in cancer patients. As the key concept of the research, mixture formulations of Dox-loaded microcapsules (Dox-M) and Fu-loaded Pluronic® hydrogels (Fu-H) or Fu-loaded diblock copolymer hydrogels (Fu-HC) have been employed as drug depots. The in vitro and in vivo drug depot was designed as a formulation of Dox-M dispersed inside an outer shell of Fu-HP or Fu-HC after injection. After intratumoral injection, Dox-M/Fu-HC produced higher inhibition effects among tumor growth than that by Dox-M/Fu-HP, while Dox-M had the weakest inhibitory effects of the tested treatments.
In conclusion, the results of this study provide a useful experimental platform for multi-drug delivery research as injectable formulations.
