Aminated Polyrotaxanes as Next-Generation Excipients: Dual Roles inStabilization and Drug Delivery of Injectable Biologics

Introduction: The instability of injectable biologics, such as monoclonal antibodies, cytokines, and enzymes, has become a major challenge in modern pharmaceutical formulation. Traditional formulation additives like PEGs, polysorbate, and sugars cannot sufficiently stabilize biologics against thermal, mechanical, and interfacial stresses. This review discusses the potential of aminated polyrotaxanes (APRs) as a next-generation biologic formulation excipient for stabilizing biologics through supramolecular interactions between biologics and formulation additives. Methods: A detailed analysis was made on the chemistry, synthesis, and functionalization of APRs, including their physicochemical interactions with biologics, formulation adaptability, and biological activities. A comparison of APRs with traditional formulation additives was based on recent research findings on their biological activities, in vitro/in vivo results, and case studies on nanomedicine and regenerative therapy. Results: The results showed that APRs exhibited better biologic stabilization ability compared to traditional formulation additives. Specifically, APRs demonstrated high retention of biologic activity (>90%) under freeze-thaw stress, improved syringeability in high-viscosity formulation systems, and improved pharmacokinetics in animal studies. APRs are biodegradable, less cytotoxic, and functionalizable for further biological activities. Discussion: In contrast to traditional stabilizers, APRs provide multifunctional, intelligent, and biocompatible solutions with substantial advantages for aggregation suppression, depot formation, and long-term bioactivity maintenance. However, challenges persist for GMP processability and regulatory acceptance, which can be improved with the aid of AI design tools and excipient safety considerations. Conclusion: Aminated polyrotaxanes represent a groundbreaking step forward in the science of excipients for the stabilization and delivery of emerging biologics. The application of aminated polyrotaxanes to mAb and mRNA therapies is promising for clinical applicability and global impact.