Protein-Polymer Delivery: Chemistry from the Cold Chain to the Clinic.

Abstract

Drug delivery is commonly thought of as the performance of a drug in vivo. Rather, the process of drug delivery can comprise of the journey of the drug from manufacturer to clinic, clinic to patient, and patient to disease. Each step of the journey includes hurdles that must be overcome for the therapeutic to be successful. Recent developments in proteinaceous therapeutics have made the successful completion of this journey even more important because of the relatively fragile nature of proteins in a drug delivery context. Polymers have been demonstrated to be an effective complement to proteinaceous therapeutics throughout this journey owing to their flexibility in design and function. During transit from manufacturer to clinic, the proteinaceous drug is threatened by denaturation at elevated temperatures. Polymers can help improve the thermal stability of the drug at ambient shipping conditions, thereby reducing the need for an expensive cold chain to preserve its bioactivity. Upon arrival at the clinic, the drug must be reconstituted into a suitable formulation that can be introduced into the patient. Unfortunately, traditional drug formulations relying on oral administration are generally not suitable for proteinaceous drugs owing to the hostile environment of the stomach. Other traditional methods of drug administration-like hypodermic injections-frequently suffer from low patient compliance. Polymers have been explored to design drug formulations suitable for alternative methods of administration. Upon entry into the body, proteinaceous drugs are at risk for identification, destruction, and excretion by the immune system. Polymers can help drugs reprogram immune system response and, in some cases, elicit a synergistic immune response. The next phase of research on protein-polymer-based therapeutics encourages a holistic effort to design systems that can survive each stage of the drug delivery journey.