Overcoming the challenges in administering biopharmaceuticals: formulation and delivery strategies

Abstract

Biopharmaceutical drugs such as antibodies, peptides and recombinant proteins have high specificity and potency compared to small molecules. These features arise from their macromolecular composition, which provides the structural complexity that is often required for specificity. However, this structural complexity means that biopharmaceutical drugs are large and susceptible to degradation, which makes it challenging to formulate and deliver them. These drugs also have reduced permeation across biological barriers, which complicates their delivery to specific sites or intracellular targets. In this Review we highlight recent advances in formulation and delivery strategies that have facilitated the transformation of product portfolios and development pipelines by this class of compounds. These advances include the use of microsphere-based sustained-release technologies, protein modification methods that make use of polyethylene glycol and other polymers, as well as genetic manipulation of biopharmaceutical drugs such as Fc- and albumin-fusions. We also highlight current and emerging delivery routes that provide alternatives to injection, including transdermal, oral and pulmonary delivery. Current areas of formulation and delivery research show promise for the application of biopharmaceutical drugs to tumour immunotherapy using nanoparticle technology, tissue engineering and enhanced approaches to cell-based therapy. These delivery methods could be used for the targeted delivery of proteins to the brain, which could have implications in the treatment of a wide range of central nervous system disorders. These technologies could potentially increase the effectiveness of conventional approaches that have not yet translated to the clinic, although they have had promising preclinical results. Intracellular delivery of proteins and peptides is a new frontier in delivery research, which could dramatically augment the breadth of targets amenable to biopharmaceutical drug therapy.