Encapsulated Docetaxel in Synthesized PCL-PEG-PCL Nano-Carriers as a Strategy for Controlled Drug Delivery in Breast Cancer

Author:

Khojastehfar Ali1,Zabihi Ebrahim1,Mostafazadeh Amrollah1,Janbabaei Ghasem2,Hakemi Pejman3,Nataj Hadi4,Mahjoub Soleiman1ORCID

Affiliation:

1. Babol University of Medical Science

2. Tehran University: University of Tehran

3. Islamic Azad University Ayatollah Amoli Branch

4. Mazandaran University of Medical Sciences

Abstract

Abstract Background Nano-drug delivery systems are rapidly evolving in the treatment of cancer due to reduced side effects and improved therapeutic properties of drugs through the drugs’ slow release and as a result, enhancing permeability and retention of drugs. Methods and Results Encapsulated docetaxel in PCL-PEG-PCL nano-carrier (P1) was prepared by the “modified nano-precipitation” method. TEM, AFM, and DLS were used for character evaluation. HPLC and dialysis bags were also used to evaluate the amount of drug release and drug encapsulation. The MCF-7, MDA-MB231, and fibroblast cell lines were treated with different concentrations of the synthesized nano-carriers loaded DTX and free DTX over 48 and 72 hours. The MTT assay was used for investigating cytotoxic effects. The Annexin-V/PI staining and Hoechst-33342 staining were performed for apoptosis assay. The characterization techniques showed the designed nano-carrier has suitable properties for carrying drugs. The percentages of encapsulation, drug loading, and drug releasing were obtained by the HPLC technique. The MTT-assay results showed that inhibition of MCF-7 and MDA-MB231 cell growth and proliferation by P1 during 72 hours is significantly higher than 48 hours. The apoptosis assays showed the cytotoxic effects of synthesized nano-carriers that cause apoptosis cell death. Conclusion The results showed that DTX is effectively encapsulated by PCL-PEG-PCL nano-carriers, which can increase the solubility and bioavailability of the drug by high penetration into the cell. The nano-carrier P1 significantly caused early apoptosis of MCF-7, and MDA-MB231 cells. Accordingly, the IC50 of P1 on MCF-7 and MDA-MB231 cells in 72 hours was reported higher than at 48 hours. Based on the results obtained, it can be concluded that controlled drug release from the designed nano-carriers has been achieved and induction of apoptotic cell death has occurred.

Publisher

Research Square Platform LLC

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