Docetaxel-Loaded Methoxy poly(ethylene glycol)-poly (L-lactic Acid) Nanoparticles for Breast Cancer: Synthesis, Characterization, Method Validation, and Cytotoxicity
Author | Abouhasera, Sanaa |
Author | Abu-Madi, Marawan |
Author | Al-Hamdani, Mohammed |
Author | Abdallah, Atiyeh M. |
Available date | 2024-03-13T05:14:56Z |
Publication Date | 2023 |
Publication Name | Pharmaceuticals |
Resource | Scopus |
ISSN | 14248247 |
Abstract | This study aimed to synthesize and characterize DTX-mPEG-PLA-NPs along with the development and validation of a simple, accurate, and reproducible method for the determination and quantification of DTX in mPEG-PLA-NPs. The prepared NPs were characterized using AFM, DLS, zetasizer, and drug release kinetic profiling. The RP-HPLC assay was developed for DTX detection. The cytotoxicity and anti-clonogenic effects were estimated using MTT and clonogenic assays, respectively, using both MCF-7 and MDA-MB-231 cell lines in a 2D and 3D culture system. The developed method showed a linear response, high precision, accuracy, RSD values of ≤2%, and a tailing factor ≤2, per ICH guidelines. The DTX-mPEG-PLA-NPs exhibited an average particle size of 264.3 nm with an encapsulation efficiency of 62.22%. The in vitro drug kinetic profile, as per the Krosmeyers–Peppas model, demonstrated Fickian diffusion, with initial biphasic release and a multistep sustained release over 190 h. The MTT assay revealed improved in vitro cytotoxicity against MCF-7 and MDA-MB-231 in the 2D cultures and MCF-7 3D mammosphere cultures. Significant inhibitions of the clonogenic potential of MDA-MB-231 were observed for all concentrations of DTX-mPEG-PLA-NPs. Our results highlight the feasibility of detecting DTX via the robust RP-HPLC method and using DTX-mPEG-PLA-NPs as a perceptible and biocompatible delivery vehicle with greater cytotoxic and anti-clonogenic potential, supporting improved outcomes in BC. |
Sponsor | Higher Education Commission (HEC) of Pakistan; project#; 6751/Punjab/NRPU/R&D/HEC/ 2016 and Researchers Supporting Project number (RSPD2023R1035), King Saud University, Riyadh, Saudi Arabia. |
Language | en |
Publisher | Multidisciplinary Digital Publishing Institute (MDPI) |
Subject | breast cancer docetaxel mPEG-PLA nanoparticles validation method |
Type | Article |
Issue Number | 11 |
Volume Number | 16 |
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Pharmacy Research [1261 items ]