Docetaxel-Loaded Methoxy poly Nanoparticles for Breast Cancer: Synthesis, Characterization, Method Validation, and Cytotoxicity

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 k...

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Bibliographic Details
Published in:Pharmaceuticals (Basel, Switzerland) Switzerland), 2023-11, Vol.16 (11)
Main Authors: Miraj, Shumaila, Saeed, Hamid, Iqtedar, Mehwish, Albekairi, Norah A, Ahmed, Nadeem, Danish, Muhammad Zeeshan, Islam, Muhammad, Rasool, Muhammad Fawad, Deen, Kashif Mairaj, Rathore, Hassaan Anwer
Format: Article
Language:English
Subjects:
Analysis
Breast cancer
Docetaxel
Ethylene glycol
High performance liquid chromatography
Lactic acid
Methods
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Summary: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.
ISSN:1424-8247
1424-8247
DOI:10.3390/ph16111600