AbstractsBiology & Animal Science

Cancer remains a major public health problem in the United States and in other developed countries. Our knowledge in tumor biology has not been accordingly translated into new substantially better anticancer drugs. The yield of new effective anticancer is low. Drug delivery and dosing regimen compose two major limitations for anticancer drug efficacy. The overall objective of the work presented in this dissertation was to optimize cancer chemotherapy. Chapters 2 and 3 contribute scientifically to the field of regional cancer chemotherapy, with a specific focus on prostate cancer. Chapters 4, 5 and 6 contribute to the different aspects of pharmacokinetics, including interspecies scaling, population pharmacokinetics, and tissue distribution. The reader will find that the work presented in this thesis spans many areas within the pharmaceutical sciences. The major conclusions and contributions of the research in this dissertation are as follows: (a) the establishment of paclitaxel loaded biodegradable implants that have desired in vitro release profile; (b) the efficacy of the drug delivery system was tested in PC-3 tumor bearing mice. The drug loaded cylinders inhibited tumor growth, while the system exposure is negligible; (c) establishment of allometric relationship across four species for low-dose suramin; (d) development and validation of empirical equations for suramin dosing regimen in dog cancer patients; (5) study of tissue distribution of low-dose suramin and development of local PKPB model. The research in this dissertation spanned multiple disciplines and covered many areas of the pharmaceutical sciences, from drug delivery to pharmacokinetics, from in vitro to in vivo. Hopefully, this work can give readers some ideas to improve the yield of new drugs.