Controlled release of therapeutic antibody formats

• Short antibody residence times of locally administered antibodies are discussed.
• Benefits of controlled release systems for therapeutic antibodies are discussed.
• Strategies for the controlled release of antibodies are elucidated.
• The general requirements and challenges for such systems are provided.
• The relation between therapeutic objective and antibody delivery is shown.

The local administration of antibodies can represent in many cases a significant improvement for antibody-based therapies. The benefits of local delivery include high drug concentrations at the target site, the possibility of lower drug dosing and less systemic drug exposure. Currently, the most relevant delivery sites for therapeutic antibodies are the posterior segments of the eye, mucosal surfaces, the articular joints and the central nervous system (CNS). In addition, the oral and pulmonary route may enable non-invasive systemic antibody delivery. However, local antibody delivery to these sites is characterized by short drug residence times and a low compliance of administration. Controlled release (CR) systems can address these limitations and, thereby, enable and improve local delivery applications by achieving long lasting local drug concentrations, improved efficacy-dosing ratios and reduced treatment-associated side effects. The requirements for CR antibody formulations are more complex compared to conventional CR systems for small molecules, and their development poses an enormous technical challenge. Therefore, the review highlights experiences and challenges gathered in the development of the different CR systems for antibodies to date. Additionally, the unmet technological needs encountered in the field are described. This includes a critical evaluation of the limited capability of various CR systems to preserve antibody stability, delivery site specific considerations, as well as the processability of a CR system with a particular focus on drug loading and injectability. We believe that the success of CR and local delivery approaches could create an enormous added value for patients in the future.

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