Recent Advances in the Development of Novel Strategies for LongCirculating Drug Formulation

INTRODUCTION: Many therapeutic agents exhibit limited clinical effectiveness due to their poor bioavailability, rapid systemic clearance, and short plasma half-life, which eventually reduce patient compliance. To address these challenges, long-circulating drug delivery systems have been introduced to prolong drug presence in the bloodstream, enhance pharmacokinetic stability, and improve therapeutic outcomes. METHODS: This narrative review was conducted through a structured literature search of the Scopus database using the keywords "long-circulating AND drug formulation" and "long-circulating AND nanoparticles," focusing on articles published between 2000 and 2024. RESULTS: This review offers a comprehensive overview of current strategies to extend drug circulation time, including PEGylation, lipidation, nucleic acid modification, and fusion technologies involving Fc and Human Serum Albumin (HSA). Additionally, the emerging cell-mediated biomimetic approaches that utilize natural biological mechanisms for targeted and sustained drug release are discussed. Furthermore, advanced formulation systems such as microencapsulation, nanocrystal suspensions, multivesicular liposomes, and biomineralization-based nanocarriers are assessed in terms of their design principles, preparation techniques, and mechanisms of controlled drug release. DISCUSSION: These findings highlight the growing importance of rational design in longcirculating drug delivery systems, where modifications at the molecular and formulation levels can significantly influence pharmacokinetic behaviour. The shift from conventional modification strategies toward biomimetic and hybrid systems reflects an evolving focus on achieving more precise and biologically responsive drug delivery. CONCLUSION: Long-circulating drug delivery systems play a vital role in overcoming pharmacokinetic limitations, enhancing drug stability, and improving therapeutic efficacy. Continued advancements in formulation strategies and emerging technologies are expected to further support the development of safer, more effective, and patient-friendly precision therapeutics.