Abstract Background Drug delivery systems (DDS) offer a promising strategy to enhance the therapeutic index of chemotherapeutic agents in colon cancer by improving tumor targeting, circulation time, and controlled drug release. Despite extensive preclinical research, a quantitative synthesis evaluating the efficacy of DDS and the influence of design parameters remains lacking. Methods We conducted a systematic review and meta-analysis of preclinical in vivo studies assessing DDS-based chemotherapy in murine models of colon cancer. A comprehensive search of PubMed, EMBASE, Scopus, Google Scholar, Cochrane CENTRAL, and ClinicalTrials.gov was performed through October 15, 2025. Outcomes included tumor growth inhibition, with subgroup analyses examining the effects of DDS platform, chemotherapeutic agent, targeting strategy, ligand type, and route of administration. Results Twenty-three studies comprising 25 experiments and 539 animals were included. Overall, DDS-based therapies significantly reduced tumor growth compared with controls ((WMD: − 557.7; 95% CI: − 716.8 to − 398.5; I²=88%; p < 0.001) and free-drug administration ((WMD: − 276.3; 95% CI: − 367.6 to − 185.1; I²=78%; p < 0.001). Both targeted and non-targeted DDS significantly reduced tumor growth compared with free drug treatment, while targeted DDS showed significantly greater efficacy than non-targeted systems (WMD: − 240.3; 95% CI: − 399.4 to − 81.25; I²=59%; p = 0.003). Although no statistically significant differences were observed between DDS platforms or chemotherapeutic agent subgroups, micelle-based systems and DDS formulations incorporating SN-38 or doxorubicin tended to show greater tumor growth reduction. Intravenous administration demonstrated significantly greater efficacy than intraperitoneal delivery, while hyaluronic acid- and aptamer-based targeting strategies achieved the largest tumor growth inhibition. Risk-of-bias assessment indicated moderate methodological quality, with variability in reporting of randomization, blinding, and sample size calculations. Conclusions DDS-based chemotherapy consistently improves antitumor efficacy in preclinical colon cancer models, with targeting strategy, platform type, chemotherapeutic agent, and administration route influencing outcomes. These findings support the rational design of DDS platforms and underscore their translational potential. Rigorous preclinical study design and standardized reporting of efficacy and safety are essential to facilitate clinical translation.
Koliqi et al. (Tue,) studied this question.