Folate receptor-mediated delivery system based on chitosan coated polymeric nanoparticles for combination therapy of breast cancer

Abstract

Combination therapy using two or more drugs with different mechanisms of action is an effective strategy for treating cancer. This is because of the synergistic effect of complementary drugs that enhances their effectiveness. However, this approach has some limitations, such as non-specific distribution of the drugs in the tumor and the occurrence of dose-dependent toxicity to healthy tissues. To overcome these issues, we have developed a folate receptor-mediated co-delivery system that improves the access of chemotherapy drugs to the tumor site. We prepared a nanoplatform by encapsulating paclitaxel (PTX) and curcumin (CUR) in poly(caprolactone)-poly(ethylene glycol)-poly(caprolactone) (PCL-PEG-PCL) co-polymer using a double emulsion method and coating nanoparticles with pH-responsive chitosan-folic acid (CS-FA) conjugate. The nanocarrier’s physicochemical properties were studied, confirming successful preparation with appropriate size and morphology. PTX and CUR could be released synchronously in a controlled and acid-facilitated manner. The dual drug-loaded nanocarrier exhibited excellent anti-tumor efficiency in MDA-MB-231 cells in vitro. The active targeting effect of FA concluded from the high inhibitory effect of dual drug-loaded nanocarrier on MDA-MB-231 cells, which have overexpressed folate receptors on their surface, compared to Human umbilical vein endothelial cells (HUVEC). Overall, the nanoengineered folate receptor-mediated co-delivery system provides great potential for safe and effective cancer therapy.

Keywords:

• Drug delivery
• PCL-PEG-PCL
• breast cancer
• controlled release
• chitosan

Acknowledgments

The authors would like to express their gratitude to the Clinical Research Development Unit of Tabriz Valiasr Hospital, Tabriz University of Medical Sciences, Tabriz, Iran for their assistance in this research. The authors would like to acknowledge the Department of Medicinal Chemistry, Faculty of Pharmacy, Tabriz University of Medical Science, and also the Drug Applied Research Center, Tabriz University of Medical Sciences, for their assistance in this research.

Ethical approval

The local ethics committee of the Tabriz University of Medical Science waived approval. All methods were carried out in accordance with relevant guidelines and regulations. Informed consent was obtained from all subjects and/or their legal guardian(s).

Consent for publication

Not applicable.

Author contributions

SJ conceptualized the research, investigation, methodology, and writing the manuscript. BJ helped to conceptualize the research and investigation. FA helped to conceptualize the research, data analysis, made substantial contributions to the interpretation of data. MF performed the interpretation of cell culture experiments. SD supervised the project, conceptualized the research, SVM helped to conceptualize the research, performed validation and data analysis, review, and editing of the final manuscript.

Disclosure statement

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

Data availability statement

Not applicable.

Additional information

Funding

This research received no specific funding from funding organizations in the public, commercial, or non-profit sectors.