Overcoming barriers to delivery of biologics by novel approaches and advanced delivery systems

Biologics is emerging as fastest growing field of drug development offering specificity and high therapeutic potential. However, their therapeutic efficacy is dependent on their route of administration and targeted delivery. Unlike small molecules, biologics face stability, permeability, solubility and immunogenicity challenges due to their inherent features. Hence tailored approaches are required in formulation development to assure their time-and site-specific action. In this review, we summarized the general and route-specific barriers that this group of drugs encounter once in contact with administration site. We listed the most common approaches to overcome the barriers and presented examples of different delivery systems that were proposed to deal with route-specific challenges. We also addressed the role devices play in assisted drug delivery and their choices related to expected use. We highlighted device-biologic combinations and discussed our perspectives on improving development using machine learning. • Inherent biological traits challenge effective delivery across administration routes. • Stability, permeability, immunogenicity and degradation remain central challenges. • Advanced lipid and polymer-based formulations improve targeted biological delivery. • Device-drug combination enhances precise, controlled and patient-friendly dosing. • Emerging systems aim for site-specific and sustained release of biologics.