Hydroxypropyl Methylcellulose Acetate Succinate (HPMCAS): A Multifunctional Polymer Platform for Colon-Targeted Drug Delivery and Advanced Colorectal Cancer Therapeutics

Hydroxypropyl Methylcellulose Acetate Succinate (HPMCAS), an amphiphilic polymer, exhibits three distinct features that facilitate regulated drug administration to the colon: pH-dependent dissolution, mucoadhesion, and stabilisation of supersaturation. The review evaluates the structural components of HPMCAS and their roles to illustrate HPMCAS's efficacy in addressing the dual challenges of hydrophobic anticancer drugs in colorectal cancer chemotherapy, characterised by low water solubility and elevated systemic toxicity. The polymer exhibits superior pharmaceutical applications due to its multifunctional properties, facilitating its use in amorphous solid dispersions, nanoparticles, hot-melt extrusion, and 3D printing, while Eudragit and PLGA polymers show subpar performance in targeted colon delivery. The potential of precision oncology is realised by crystallisation inhibition, pH-triggered release, and receptor-targeted administration, utilising ligand conjugation to CD44, EGFR, and folate. The review identifies three primary challenges: hygroscopicity, scalability, and long-term stability, while proposing AI-assisted formulation optimisation and multi-mechanistic hybrid systems as potential solutions. HPMCAS evolves from a fundamental excipient through polymer chemistry to molecular targeting, becoming an innovative drug-delivery system that enhances the efficacy of CRC treatment while minimising adverse side effects.