Linear-Dendritic Polymers for Drug Delivery

Colloidal drug delivery systems offer a promising approach for the treatment of cancer. These systems are able to encapsulate a large amount of drug, stabilize it and protect the drug until delivery. In addition, colloidal nanoparticles of a certain size range are able to avoid renal exclusion and reticulo-edothelial system (RES) clearance, thereby increasing circulation times. Because of their long circulating times, these nanoparticles are able to extravagate into the leaky vasculature of tumor tissue. Since the lymphatic drainage system for tumor tissues are poorly developed, the end result is the accumulation of the colloidal nanoparticles in tumors. This effect is known as the enhanced permeation and retention effect (EPR). This passive targeting of tumor tissue could be enhanced with active targeting by taking advantage of cancer cell ligand-receptor interactions.

Targeted delivery systems offer a great deal of promise in expanding the therapeutic window of many existing cancer drugs. They do so by increasing delivery to target tissue, allowing a lower dosage of drugs to be used. Targeting systems like these are potentially able to reduce non-specific delivery of cancer drugs, thereby reducing the side effects of cancer while increasing therapeutic potency. A linear dendritic amphiphilic copolymer that self assembles in solution is being developed as a potential drug delivery carrier. The hydrophobic linear block forms the core, which encapsulates hydrophobic drugs while the hydrophilic dendron forms the outer shell, on which targeting ligands can be presented. Variables such as ligand density and arrangement, drug loading capacity, drug release rates and particle size can be controlled. The proposed polymer system will take advantage of the increased strength of multivalent ligand-receptor interactions for targeting.