Indexed on: 27 Nov '14Published on: 27 Nov '14Published in: Expert opinion on drug delivery
A major problem with conventional antitumor therapeutics is nonselective delivery of cytotoxic drugs to normal vital organs and tissues but little delivery to tumor tissues.Here, the authors describe the tumor selective delivery of antitumor drugs by taking advantage of nano-sized drugs and the means to augment it further. Based on the enhanced permeability and retention (EPR) effect, the mechanism for more efficient universal tumor delivery using macromolecular drugs to cover wider tumor types than single molecular target is discussed. Unique properties of solid tumor vasculature in the tumor tissue are discussed, especially leakiness of the blood vessels and factors involved and impaired clearance of macromolecular drugs from the tumor interstitium via the lymphatic system. The criteria for such macromolecular drugs or nanomedicines for effective accumulation at tumor sites is commented on as well as the importance of long plasma retention time of such drugs and a need to release active principles from nanoparticles at target sites. Methods to augment the EPR effect and tumor delivery (2 - 3 times) and its application to photodynamic therapy are also discussed.Tumor selective delivery of antitumor drugs based on the EPR effect can be accomplished and augmented by modulating the tumor environment. This methodology is favorable not only for tumor therapy but also for tumor imaging.