Advancing Drug Delivery with Biodegradable Molecularly Imprinted Polymers: From Design to Clinical Prospects

Abstract: Molecularly imprinted polymers (MIPs) have emerged as promising materials for drug delivery systems, offering various advantages in terms of selectivity, stability, modified/smart release properties, and targeted therapy. Despite decades of development, the clinical translation of MIP-DDS remains limited, mainly due to concerns regarding long-term safety, biodegradability, and regulatory acceptance. To overcome these limitations, current research focuses on designing MIP-DDS by incorporating degradable monomers, crosslinkers, and polymer architectures. The selection of monomers and crosslinkers, as well as polymerization strategies, critically influences not only the efficiency of the recognition sites formed but also the rate of degradation and drug release, which can occur through stimuli-responsive bond cleavage, hydrolysis, or surface erosion. Beyond synthetic considerations, systemic evaluation of the biocompatibility, toxicity, and degradation mechanisms of MIP-DDS is essential to support regulatory approval and clinical implementation. Therefore, this article discusses current advances, key design strategies, degradation mechanisms, and translational challenges of biodegradable MIP-DDS, highlighting the development of clinically viable imprinted drug delivery platforms. Flowchart of MIP drug delivery system, biodegradable material selection and degradation mechanisms.The flowchart illustrates the progression of Molecularly Imprinted Polymers as Drug Delivery Systems (MIP-DDS). It begins with MIP as a drug delivery system, highlighting high selectivity, controlled and smart release and targeted therapy. Concerns about long-term safety and toxicity lead to the next stage: biodegradable MIP-DDS. This involves biodegradable material selection, including monomer and crosslinker and polymerization strategies such as conventional and core/surface imprinting. The final section details degradation mechanisms of biodegradable MIP-DDS, including stimuli-responsive bond cleavage (pH, light, redox species), hydrolysis bond cleavage and surface erosion. Keywords: molecularly imprinted polymer, drug delivery system, biodegradable MIP, modified release, stimuli-responsive