Overcoming the challenges in administering biopharmaceuticals: formulation and delivery strategies

Biological drugs offer high specificity and potency, but their formulation and delivery pose substantial challenges. Here, the authors highlight recent advances in formulation strategies, describe current and emerging delivery routes and review the potential of targeted and intracellular delivery of biologics. The formulation and delivery of biopharmaceutical drugs, such as monoclonal antibodies and recombinant proteins, poses substantial challenges owing to their large size and susceptibility to degradation. In this Review we highlight recent advances in formulation and delivery strategies — such as the use of microsphere-based controlled-release technologies, protein modification methods that make use of polyethylene glycol and other polymers, and genetic manipulation of biopharmaceutical drugs — and discuss their advantages and limitations. We also highlight current and emerging delivery routes that provide an alternative to injection, including transdermal, oral and pulmonary delivery routes. In addition, the potential of targeted and intracellular protein delivery is discussed.