Design, Synthesis, and Comparison of PLA-PEG-PLA and PEG-PLA-PEG Copolymers for Curcumin Delivery to Cancer Cells

Abstract

Curcumin (CUR) has potent anticancer activities, and its bioformulations, including biodegradable polymers, are increasingly able to improve CUR’s solubility, stability, and 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 CUR-delivery capacity and inhibitory potency on MCF-7 breast cancer cells. Molecular dynamics simulations and free energy analysis 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. To characterize the copolymer synthesis, Fourier transform-infrared (FT-IR) and proton nuclear magnetic resonance (1H-NMR) were employed, copolymer size was measured using dynamic light scattering (DLS), and their surface charge was determined by zeta potential analysis. Characterization indicated that the ring-opening polymerization (ROP) reaction was optimal for synthesizing high-quality polymers. Microspheres comprising the copolymers were then 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-CUR 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. Through the integration of nano-informatics and in vitro approaches, our study determined that PLA-PEG-PLA-CUR is an optimal system for delivering curcumin to inhibit cancer cells.

Application of Pistacia atlantica Pickering emulsion‐filled chitosan gel for targeted delivery of curcumin

“…Then, it was completely washed in distilled water. To examine the stability of the emulsions, the fresh Pickering emulsion (5.0 mL) and hydrogel (2.0 g) were packed into a dialysis bag with a 14 kDa cutoff (Rostami et al., 2023 ; Shahbazizadeh et al., 2022 ). Then, it was immersed in 200 mL of gastric juice, under magnetic stirring at 100 rpm and consequently transferred to intestinal release medium on a magnetic stirrer (150 rpm) at a constant temperature (37°C) (Shahbazizadeh et al., 2022 ).…”

Application of biodegradable microsphere injections: an anticancer perspective

“…The above results fully demonstrated that the modified pH-sensitive PLA microspheres could improve the anticancer effect. Neda Rostami et al 21 synthesized (PLA–PEG–PLA) and (PEG–PLA–PEG) and showed by molecular dynamics simulations and free energy analysis that PLA–PEG–PLA has a higher tendency to interact with the cell membrane and more negative free energy, indicating that PLA–PEG–PLA is a better carrier for cell membrane penetration. Furthermore, PLA–PEG–PLA exhibited higher drug loading and more controlled release rates, leading to greater cell death in MCF-7 breast cancer cells, probably because of the stronger hydrophobicity of PLA–PEG–PLA than PEG–PLA–PEG.…”