Long-acting injectable biologics: a game-changer in immunopharmacology

Long-acting injectable (LAI) biologics, a class of agents consisting of a biologically active compound – the active pharmaceutical ingredient (API) – and polymers that form a microparticle, suspension, or hydrogel, have recently emerged as a potentially revolutionizing modality in immunopharmacology. LAIs are a type of controlled drug delivery system administered parenterally via deep and lateral muscle tissue or the fat layer below the skin. After injection, the polymers biodegrade gradually, and the API is released slowly within a therapeutic window that lasts from weeks to months. Due to its multi-daily oral administration, LAIs offer several advantages, primarily enhanced compliance, better control of plasma levels by avoiding spikes, reduced risk of human error, and the potential for use in cases of psychophysical syndromes. In recent years, the biotech industry has invested heavily in biologics research and development, resulting in the increasing use of biologic APIs and pharmaceutical excipients in nanoformulations for novel LAI products. This new generation of LAIs may alter the pharmacokinetic profile and injection site response, thereby changing and broadening the histological and immunohistochemical aspects of the long-residing depot created at the injection site. Thus, investigating LAI formulations is of the utmost importance. The novelty and complexity of these agents make it essential to assess the potential risks associated with their use and to promote pre-market managerial strategies to mitigate such risks. Therefore, this manuscript aims to provide a systematic analysis of the toxic and inflammatory responses to therapeutic LAI formulations in rodent and non-rodent models.