Khan Mohammad Sakib, Rehman Urushi, Alqahtani Taha, Al Shmrany Humood, Gupta Garima, Goh Khang Wen, Sahebkar Amirhossein, Kesharwani Prashant
Department of Pharmaceutics, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi, 110062, India.
Department of Pharmacology, College of Pharmacy, King Khalid University, Abha, 62529, Saudi Arabia.
Mol Cancer. 2025 Nov 13;24(1):288. doi: 10.1186/s12943-025-02435-2.
Colorectal cancer (CRC) is among the most prevalent malignancies globally, with a notably higher incidence in men. Despite the availability of multiple chemotherapeutic options, clinical efficacy remains limited due to poor drug solubility, restricted intestinal absorption, rapid systemic clearance, and multidrug resistance. Poly(lactic-co-glycolic acid) (PLGA), a well-established biodegradable and biocompatible copolymer, has gained significant attention for its potential in developing advanced drug delivery systems. Its tuneable degradation kinetics governed by the lactic-to-glycolic acid ratio enable precise modulation of drug release profiles. PLGA-based nanocarriers offer several therapeutic advantages, including improved solubility, extended colonic retention, and targeted delivery of anticancer agents. Furthermore, surface functionalization with copolymers, ligands, or stimuli-responsive moieties has demonstrated enhanced cellular uptake, tumor specificity, and cytotoxicity against CRC cells. This review highlights the recent developments in the synthesis, functional design, and biomedical application of PLGA nanocarriers in CRC treatment, emphasizing their role in overcoming key challenges such as chemoresistance and off-target toxicity. These advancements underscore the potential of PLGA-based polymeric systems in enhancing the therapeutic index and translational viability of anticancer therapies.
