Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Design, Synthesis, and Comparison of Pla-Peg-Pla and Peg-Pla-Peg Copolymers for Curcumin Delivery to Cancer Cells

Neda Rostami
,
Farzaneh Faridghiasi
,
Aiada Ghebleh
,
Hadi Noei
ORCID logo ,
Meisam Samadzadeh
,
Mohammad Mahmoudi Gomari
,
Mahsa Khoramipour
,
Alireza Tajiki
,
Majid Abdouss
,
Alireza Aminoroaya Yamini
ORCID logo ,
Manisha Kumari
,
Vladimir N. Uversky
* ORCID logo ,
Bryan Ronain Smith
* ,
Reza Heidari
* ORCID logo
Version 1 : Received: 26 June 2023 / Approved: 27 June 2023 / Online: 27 June 2023 (10:23:03 CEST)

A peer-reviewed article of this Preprint also exists.

Rostami, N.; Faridghiasi, F.; Ghebleh, A.; Noei, H.; Samadzadeh, M.; Gomari, M.M.; Tajiki, A.; Abdouss, M.; Aminoroaya, A.; Kumari, M.; Heidari, R.; Uversky, V.N.; Smith, B.R. Design, Synthesis, and Comparison of PLA-PEG-PLA and PEG-PLA-PEG Copolymers for Curcumin Delivery to Cancer Cells. Polymers 2023, 15, 3133. Rostami, N.; Faridghiasi, F.; Ghebleh, A.; Noei, H.; Samadzadeh, M.; Gomari, M.M.; Tajiki, A.; Abdouss, M.; Aminoroaya, A.; Kumari, M.; Heidari, R.; Uversky, V.N.; Smith, B.R. Design, Synthesis, and Comparison of PLA-PEG-PLA and PEG-PLA-PEG Copolymers for Curcumin Delivery to Cancer Cells. Polymers 2023, 15, 3133.

Abstract

Curcumin (CUR) is a phytochemical with potent anticancer activities as demonstrated by both preclinical and clinical studies. CUR bioformulations, including loading in biodegradable polymers, have been explored to increase CUR’s solubility and chemical stability, control its release, and improve its delivery to cancer cells. In this study, copolymers comprising poly (L-lactide)-poly (ethylene glycol)-poly (L-lactide) (PLA-PEG-PLA) and poly (ethylene glycol)-poly (L-lactide)-poly (ethylene glycol) (PEG-PLA-PEG) were designed and synthesized to assess and compare their curcumin delivery capacity and inhibitory potency on MCF-7 breast cancer cells. Molecular dynamics simulations indicated that PLA-PEG-PLA has a higher propensity to interact with the cell membrane and more negative free energy, suggesting it is the better carrier for cell membrane penetration. Our characterization indicated that the microsphere copolymers were synthesized successfully. Of the two formulations, PLA-PEG-PLA experimentally exhibited better results, with an initial burst release of 17.5%, followed by a slow, constant release of the encapsulated drug up to 80%. PLA-PEG-PLA-curcumin showed a significant increase in cell death in MCF-7 cancer cells (IC50 = 23.01 ± 0.85 µM) based on the MTT assay. These data were consistent with gene expression studies of Bax, Bcl2, and hTERT which showed that PLA-PEG-PLA-CUR induced apoptosis more efficiently in these cells. Our study integrates in vitro and in silico approaches to identify an optimal co-polymer for the delivery of CUR to cancer cells.

Keywords

Breast Cancer; Curcumin; Copolymer; Drug delivery; Nanoinformatics

Subject

Biology and Life Sciences, Biology and Biotechnology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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