Biopolymer hydrogel matrices for the stabilization and in-vitro delivery of anti-cancer polyoxometalate [CoW₁₁O₃₉(CpTi)]⁷⁻

Abstract

In the present study, the polyoxometalate (POM), [CoW₁₁O₃₉(CpTi)]⁷⁻, known for its significant anti-cancer activity and relatively low toxicity compared to established organic drugs such as CP and 5FU, is investigated. However, it is acknowledged that POMs inherently exhibit toxicity to living cells due to the presence of heavy and toxic metal ions within their core structures and their limited selectivity toward biological targets. Consequently, a methodology to mitigate this toxicity is sought by encapsulating these POMs within hydrogel matrices, with the intention to facilitate slow, sustained release and enhanced target specificity. In this study, the hydrogel of the well-researched anti-cancer POM, K₆H[CoW₁₁O₃₉(CpTi)] (hereafter abbreviated as CoW₁₁CpTi), is synthesized through the electrostatic interaction of the positively charged carboxymethyl chitosan (CMC), carboxymethyl cellulose (CMCell), and gelatin, which serve as hydrogelators. Subsequent characterization of the resultant CMC-CoW₁₁CpTi, CMCell-CoW₁₁CpTi, and gelatin-CoW₁₁CpTi gels is performed utilizing Fourier Transform Infrared Spectroscopy (FT-IR), Differential Scanning Calorimetry/Thermogravimetric Analysis (DSC/TGA), Electron Spin Resonance (ESR) Spectroscopy, Scanning Electron Microscopy (SEM), and T_gel analysis. Among these, the gelatin-CoW₁₁CpTi gel demonstrates the highest stability, retaining its structural integrity for in excess of 10 days. In addition, cytotoxicity assays are conducted on an assortment of cell lines including NRK52e (Rattus norvegicus kidney cell line), MDA-MB-231 (human breast adenocarcinoma), and MCF-7 (human breast epithelial adenocarcinoma). It is observed that the release of POM from the hydrogel matrices under physiological pH conditions exhibits a slow and sustained profile. This study therefore offers a promising approach for the effective delivery of POMs in cancer therapy.

Graphical Abstract

HIGHLIGHTS

• Anti-cancer polyoxometalate (POM) and its encapsulation in hydrogel is optimized.

• Stabilization and release study of the POM from gel matrix is explored.

• Suppression of toxicity is evaluated using in-vitro MTT assay.

• Gelatin gel can be used to design and produce novel drug delivery system.

Keywords:

• Anti-cancer polyoxometalates
• supramolecular hydrogels
• drug delivery
• in-vitro studies
• carboxymethyl chitosan
• carboxymethylcellulose

Acknowledgments

Authors V.M.P. and S.A.J. acknowledge Department of Science and Technology (DST), Ministry of Science and Technology, Government of India (GoI) for financial assistance through Fast-Track Scheme No. SR/FT/CS-133/2011.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Authors’ contribution

V.M.P. and S.A.J. conceived and designed the experiments; V.M.P. performed the experiments; V.M.P. and D.G. analyzed the data. V.M.P. and D.G. wrote the manuscript whereas, S.A.J. reviewed the manuscript and supervised the research.

Additional information

Funding

This work was supported by Department of Science and Technology (DST), Ministry of Science and Technology, India.