99mTc-labeled and pH-awakened microbeads entrapping surface-modified lipid nanoparticles for the augmented effect of oxaliplatin in the therapy of colorectal cancer.

Rajpoot, Kuldeep; Jain, Sunil K

Aim: The present study was aimed to develop Eudragit S100-coated, pH-awakened microbeads (MBs) encapsulating folic acid (FA)-modified tristearin solid lipid nanoparticles (SLNs) loaded with oxaliplatin (OP). Afterward, these formulations were evaluated (in vitro and in vivo) for their potential against CRC.Methods: The SLNs were synthesized by employing the solvent diffusion technique, and then they were entrapped in the MBs. The prepared uncoupled and coupled SLNs (SLN-OP and FA-SLN-OP, respectively) were examined for in vitro cytotoxicity effect against COLO-205. Gamma-scintigraphy study was used for determining biodistribution (in vivo) of drug in different organs through MBs.Results: Outcomes for FA-SLN-OP revealed more cytotoxicity (IC50 = 6.8 µg/ml) against COLO-205 cells (in vitro) than OP solution (50% inhibitory concentration (IC50) = 8.0 µg/ml) and SLN-OP (IC50 = 7.5 µg/ml). MBs were also investigated in vivo using Gamma-scintigraphy study. After 48 h study, 99mTc-EuB-FA-SLN-OP confirmed an elevated level of drug in the colonic tumor, which was found significantly (p < 0.0001) higher than that of 99mTc-EuB-SLN-OP.Conclusions: In conclusion, developed MBs formulation (99mTc-EuB-FA-SLN-OP) suggested promising results against therapy of CRC using dual targeting (i.e., ligand-directed and pH-awakened) approach.