# Preparation and Anti-cancer Evaluation of Methotrexate-loaded Inositol-6 Phosphate Cross-linked Chitosan Nanoparticles on Breast Cancer

**Authors:** Masoud Farshbaf, Nasrin Gobakhlou, Muhammad Sarfraz, Javid Shahbazi-Mojarrad, Mohammad Feyzizadeh, Hamed Hamishehkar, Parvin Zakeri-Milani, Hadi Valizadeh

PMC · DOI: 10.34172/apb.43661 · Advanced Pharmaceutical Bulletin · 2025-03-08

## TL;DR

Researchers developed chitosan nanoparticles using inositol hexaphosphate to deliver methotrexate, finding them more effective against breast cancer cells than traditional methods.

## Contribution

The study introduces inositol hexaphosphate as a novel, cost-effective cross-linker for chitosan nanoparticles with improved drug delivery performance.

## Key findings

- InsP6-crosslinked chitosan nanoparticles showed higher methotrexate encapsulation efficiency than TPP-crosslinked nanoparticles.
- InsP6CNsMTX exhibited the strongest antitumor effect on MCF-7 cells after 24 hours compared to other formulations.
- InsP6CNs and TPPCNs had similar cell uptake behavior in MCF-7 cells despite differences in size and zeta potential.

## Abstract

Chitosan nanoparticles (CNs) have directed considerable research efforts towards developing biocompatible, biodegradable, inexpensive and efficient particulate drug delivery systems.

In the present investigation, we utilized green and safe inositol hexaphosphate (InsP6) as a physical cross-linker to obtain CNs (InsP6CNs) and compared their size, zeta potential and cell uptake ability with the CNs cross-linked with tripolyphosphate (TPP) as a commonly used cross-linker (TPPCNs). Methotrexate (MTX) as the model drug was physically incorporated within the both types of CNs (InsP6CNsMTX and TPPCNsMTX) and their time-dependent anti-cancer behavior was evaluated on MCF-7 cell line.

Compared to TPPCNs, InsP6CNs were bigger in hydrodynamic diameter and showed far different zeta potential value. The MTX encapsulation efficiency was much higher for InsP6CNsMTX than that of TPPCNsMTX. InsP6CNs and TPPCNs showed similar in vitro cell uptake behavior, examined on MCF-7 cell line. Furthermore, after 24 h, InsP6CNsMTX had the most in vitro antitumor effect on the MCF-7 cells, compared to free MTX and TPPCNsMTX.

Consequently, InsP6 can be presented as an accessible and cost-effective member of physical cross-linkers to prepare efficient CNs as drug delivery systems.

## Linked entities

- **Chemicals:** Methotrexate (PubChem CID 4112), inositol hexaphosphate (PubChem CID 890), chitosan (PubChem CID 129662530)
- **Diseases:** breast cancer (MONDO:0004989)

## Full-text entities

- **Diseases:** cancer (MESH:D009369), Breast Cancer (MESH:D001943)
- **Chemicals:** TPP (MESH:C005692), Chitosan (MESH:D048271), Inositol-6 Phosphate (-), MTX (MESH:D008727), inositol hexaphosphate (MESH:D010833)
- **Cell lines:** MCF-7 — Homo sapiens (Human), Invasive breast carcinoma of no special type, Cancer cell line (CVCL_0031)

## Full text

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## Figures

4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12235370/full.md

## References

17 references — full list in the complete paper: https://tomesphere.com/paper/PMC12235370/full.md

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Source: https://tomesphere.com/paper/PMC12235370