Oral delivery of pH-responsive alginate microbeads incorporating folic acid-grafted solid lipid nanoparticles exhibits enhanced targeting effect against colorectal cancer: A dual-targeted approach.

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.