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

Abstract

Aim

This 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 colorectal cancer (CRC).

Methods

The SLNs were synthesised 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 (50% inhibitory concentration [IC₅₀] = 6.8 µg/ml) against COLO-205 cells (in vitro) than OP solution (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 tumour, 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.

Keywords:

• Colorectal cancer
• Eudragit S100
• microbeads
• oxaliplatin
• cytotoxicity study
• COLO-205

Acknowledgements

One of the authors, Kuldeep Rajpoot, is thankful to UGC New Delhi for awarding Central University Fellowship to carry out the research work. The authors are grateful to Chirayu Cancer Hospital, Bhopal, for providing necessary facilities to carry out Gamma-Scintigraphy and Biodistribution study.

Disclosure statement

The authors declare no conflict of interest.

Additional information

Funding

This work was supported by the University Grants Commission (Central University Fellowship).