To achieve an enhanced anticancer effect of
drug to treat
colorectal cancer, a dual-targeted (i.e.,
ligand-tailored and pH-triggered) multiparticulate system has been designed to deliver
drug directly into the colon domain. In this regard,
folic acid-grafted solid
lipid nanoparticles (SLNs) bearing
irinotecan were encapsulated in
microbeads of
alginates. Afterward, these
microbeads were coated with enteric
polymer (i.e.,
Eudragit S100) to make them pH-responsive. COLO-205 cells were used to determine in vitro cytotoxicity potential of various formulations. Findings for IHT loaded FA-coupled SLNs suggested significantly (p < 0.05) higher cytotoxic effect against COLO-205 cells (in vitro) as compared to
drug solution and uncoupled SLNs. Further, the
microbeads incorporating SLNs were evaluated for drug release in various simulated gastrointestinal fluids (i.e., pH, 1.2, 4.5, 7.4, and 6.8). Findings confirmed the release of the
drug in the intestinal region only (i.e., pH > 7.0). In therapeutic experiments (in vivo), the optimized radiolabeled
microbeads (99mTc-EuBIRSLN3 and 99mTc-EuBIRSLNF3) were administered via oral route to Balb/c mice. The results suggested that FA-coupled
microbeads (99mTc-EuBIRSLNF3) distributed higher (19.62 ± 0.78%) amount of
drug (i.e., 99mTc-IHT/g of tissue) as compared to uncoupled
microbeads (99mTc-EuBIRSLN3, 7.63 ± 0.49%) in the colon
tumor after 48 h, which confirmed its targeting ability to the
tumor in the colon region. Further, 99mTc-EuBIRSLNF3 showed significantly (p < 0.01) higher antitumor effect against HT-29 cells bearing Balb/c mice over uncoupled
microbeads and advocated their potential for enhanced antitumor efficacy for the treatment of
colorectal cancer.