A robust optimization approach for the breast cancer targeted design of PEtOx-b-PLA polymersomes


ÖZ U. C., Bolat Z. B., Ozkose U. U., Gulyuz S., KÜÇÜKTÜRKMEN B., PARLAK KHALİLY M., ...More

MATERIALS SCIENCE & ENGINEERING C-MATERIALS FOR BIOLOGICAL APPLICATIONS, vol.123, 2021 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 123
  • Publication Date: 2021
  • Doi Number: 10.1016/j.msec.2021.111929
  • Journal Name: MATERIALS SCIENCE & ENGINEERING C-MATERIALS FOR BIOLOGICAL APPLICATIONS
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Aerospace Database, Biotechnology Research Abstracts, Chemical Abstracts Core, Communication Abstracts, Compendex, EMBASE, INSPEC, MEDLINE, Metadex, Civil Engineering Abstracts
  • Keywords: Central composite design, Doxorubicin, Peptide18, PEtOx-PLA, Polymersome, Targeted delivery
  • Hacettepe University Affiliated: Yes

Abstract

The equipping of nanoparticles with the peptide moiety recognizing a particular receptor, enables cell or tissue specific targeting, therefore the optimization of the targeted nanoparticles is a key factor in the formulation design process. In this paper, we report the optimization concept of Doxorubicin encapsulating PEtOx-b-PLA polymersome formulation equipped with Peptide18, which is a breast cancer recognizing tumor homing peptide, and the unveiling of the cell-specific delivery potential. The most dominant formulation parameters, which are the polymer to Doxorubicin mass ratio (w/w) and the aqueous to organic phase ratio (v/v), were optimized using Central Composite Design (CCD) based Response Surface Methodology. The characteristics of optimum polymersome formulation were determined as the hydrodynamic diameter of 146.35 nm, the PDI value of 0.136, and the encapsulation efficiency of 57.11% and TEM imaging, which are in agreement with the DLS data, showed the spherical morphology of the polymersomes. In order to demonstrate the breast cancer-specific delivery of targeted polymersomes, the flow cytometry and confocal microscopy analyses were carried out. The targeted polymersomes were accumulated 8 times higher in AU565 cells compared to MCF10A cells and the intracellular Doxorubicin was almost 10 times higher in AU565 cells. The CCD-mediated optimized targeted polymersomes proposed in this report holds the promise of targeted therapy for breast cancer and can be potentially used for the development of novel treatments.