Glutamate-Leucine Block Copolypeptides for Drug Delivery

Chemotherapy treatments involving the delivery of naked drugs to the body must overcome many complications such as poor solubility, enzymatic degradation, and clearance from the body, all of which can result in the drug having a short circulation half-life, low efficacy, and undesirable side effects. One solution to overcome these problems is to encapsulate the drug within a nano-sized drug delivery vehicle. Nano-sized drug delivery vehicles are advantageous since they can protect the drug from degradation during its circulation in the body, release the drug in a controlled manner, and provide passive targeting to the tumor tissue. Many materials for drug delivery vehicles have been investigated. Liposomes, which are vesicles composed of natural or synthetic phospholipids, have been thoroughly investigated, and many liposomal formulations have been successful in the market. However, one limitation of liposomes is that they are less stable due to being comprised of relatively smaller molecules that exhibit weaker attractive interactions in a self-assembled vesicle. This disadvantage has motivated the development of other materials for drug delivery such as synthetic polymers, which are longer molecules that can exhibit stronger attractive interactions in a self-assembled vesicle. Synthetic control of the polymers also allows for fine tuning of the hydrophilic and hydrophobic chain lengths. Another material that has been recently gaining popularity for use in drug delivery is the polypeptide. These amino acid-based building blocks provide further advantages. Similar to polymers, monodisperse polypeptides can be synthesized with precise control due to recent advances in polymerization techniques, and the longer chains provide stability for the self-assembled vesicles. They are also naturally occurring and have the potential to be biocompatible. These polypeptides can also adopt secondary structures to further improve the stability of the vesicles. Our laboratory previo