Anticancer Analysis of CD44 Targeted Cyclosporine Loaded Thiolated Chitosan Nanoformulations for Sustained Release in Triple-Negative Breast Cancer

Int J Nanomedicine. 2023 Oct 11:18:5713-5732. doi: 10.2147/IJN.S424932. eCollection 2023.

Abstract

Introduction: Cyclosporine (CsA), a potent immunosuppressive chemotherapeutic medication, treats numerous cancers, particularly malignant carcinoma, acute leukemia, and triple-negative breast cancer (TNBC).

Methodology: A specified polymeric nanoformulation (NF) based drug delivery technique with ligand functionalization at the surface was developed to improve its delivery at the intended area and boost the efficacy for prolonged time. The in silico verified the HA binding to the CD44 receptor at binding sites A and B in triple-negative breast cancer cells. The NF of encapsulated Cyclosporine in thiolated chitosan (TC) with the outermost coating of hyaluronic acid (HA) was formulated and characterized.

Results: So, the zeta analysis revealed a particle size of 192 nm and PDI of 0.433, zeta potential of 38.9mV. FTIR and Raman investigations also support the existence of hydrophobic groups, porous surfaces, and non-clumping characteristics. While XRD verified its crystallographic nature while SEM and TEM analysis revealed the spherical nanoparticles with sleek exteriors. DSC demonstrated the stability of NF at high temperatures. The NF showed 85% drug encapsulation followed Higuchi release model for therapeutic moiety at acidic pH for a maximum of 72 hours. When compared to raw Cyclosporine, the in vitro tumor cell inhibition of ThC-HA encapsulated with Cyclosporine was tested using an MTT dye on normal breast epithelial cells compared to triple-negative breast cancer cells.

Conclusion: This novel formulation improved the long-term viability, effectiveness, and active targeting as an effective and potent therapeutic moiety against cancer.

Keywords: CD44; breast cancer; cyclosporine; hyaluronic acid; nanoformulations; targeted chemotherapeutic drug delivery; thiolated chitosan; triple-negative breast cancer.

MeSH terms

  • Cell Line, Tumor
  • Chitosan* / chemistry
  • Cyclosporine / pharmacology
  • Cyclosporine / therapeutic use
  • Delayed-Action Preparations / therapeutic use
  • Drug Carriers / chemistry
  • Humans
  • Hyaluronan Receptors / metabolism
  • Hyaluronic Acid / chemistry
  • Nanoparticles* / chemistry
  • Triple Negative Breast Neoplasms* / drug therapy
  • Triple Negative Breast Neoplasms* / pathology

Substances

  • Chitosan
  • Cyclosporine
  • Delayed-Action Preparations
  • Hyaluronic Acid
  • Drug Carriers
  • CD44 protein, human
  • Hyaluronan Receptors

Grants and funding

This research work was funded by Institutional Fund Projects under grant no. (IFPIP: 824-290-1442). Therefore, authors gratefully acknowledge technical and financial support from the Ministry of Education and King Abdulaziz University, DSR, Jeddah, Saudi Arabia.