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Transcending Nano-Encapsulation: Engineering Campesterol-Loaded Shellac-PLGA Nanosystem for Breast Cancer Therapy
Hamid Saeed Shah1, Samia Ghani2,3, Faisal Usman4
1Institute of Pharmaceutical Sciences, University of Veterinary and Animal Sciences, Lahore, 54000, Pakistan.
Introduction:
This study aimed to fabricate and characterize shellac (SH)-PLGA coated plant-derived phytosterol, campesterol (CS) nanoparticles (NPs) for breast cancer therapy.
Methods:
The nanoparticles were prepared using a nanoprecipitation technique and exhibited a mean size of 120.13 ± 10.29 nm, with PDI = 0.0461 ± 0.0028, and surface charge = -29.35 ± 6.07 mV.
Results:
In vitro percent cell death screening revealed potent anticancer activity of CS-SH-PLGA-NPs against triple-negative breast cancer cells (MDA-MB-231), yielding an IC5 0 of 13.57 ± 6.721 µM, significantly lower than pure CS (IC5 0 = 25.79 ± 5.813 µM). Flow cytometry and genotoxic assays further confirmed their apoptotic potential. In vivo evaluation in five groups of albino female mice demonstrated an enhanced tumor regression rate (3.76 ± 0.81%) compared with pure CS (3.17 ± 0.42%). Molecular docking revealed stronger binding affinity of PLGA (CScore = 1.23) with CS than SH (CScore = 0.88), with interactions at key residues of CDK2, EGFR, and Caspase-3. The electronic reactivity predicted by DFT was consistent with the overall computational findings.
Conclusion:
Taken together, these findings indicate that CS-SH-PLGA-NPs may serve as a promising nanoplatform for the treatment of breast cancer.

