Cyclodextrin-Based Pseudocopolymers and Their Biomedical Applications for Drug and Gene Delivery

Cyclodextrin (CD)-based pseudocopolymers draw on the host-guest inclusion complex properties of CDs, particularly β-CD, to form noncovalent connections with compatible guest molecules. This approach enhances the structural versatility and biocompatibility of the resulting polymer blocks. Host-guest chemistry enables the assembly of sophisticated architectures, such as comb-like grafts, star structures, and dendrimer-like forms, which are engineered for targeted, stimuli-responsive, and sustained drug release. Several innovative systems, including pH-sensitive micelles, redox-responsive nanoparticles, and dual-responsive hydrogels that provide high drug-loading capacity, controlled release, and tumor-targeted delivery, are discussed. Applications in drug and gene therapy are highlighted, where CD-based pseudocopolymers increase drug loading and transfection efficiency, reduce cytotoxicity, and facilitate the precise delivery of therapeutic agents, such as DNA and small interfering RNA. This review showcases the potential of CD-based pseudocopolymers as adaptable platforms for advanced drug and gene delivery, addressing numerous challenges posed by biological barriers, multidrug resistance, and the need for targeted therapies through rational system design. Future directions emphasize optimizing these systems for clinical translation, focusing on refining synthetic methodologies, enhancing molecular modularity, and achieving a deeper understanding of their biological compatibility.