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Life sciences · Journal article
Pakistan Journal of Pharmaceutical Sciences · November 2, 2026
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Abstract: Background: Nanoparticles have gained considerable attention as versatile platforms for the diagnosis and treatment of different diseases, particularly cancer. Lipid-coated hybrid nanoparticles (LCHNPs), comprising a polymeric core enveloped by a lipid shell, offer improved targeting and potential solutions for multidrug-resistant cancers. Objective: To develop and preclinically evaluate a dual-drug LCHNP system co-delivering Tamoxifen and Gemifloxacin for enhanced breast cancer therapy. Methods: An experimental in-vitro and in-vivo study was conducted to develop and evaluate lipid-coated hybrid nanoparticles (LCHNPs) co-delivering Tamoxifen and Gemifloxacin using MCF-7 cells and a DMBA-induced mammary tumor model in female Albino Wistar rats.Poly(lactic-co-glycolic acid) (PLGA) nanoparticles loaded with Tamoxifen were prepared by the solvent evaporation method and liposomes loaded with Gemifloxacin were prepared by the thin-film hydration technique. The two systems were subsequently fused to generate LCHNPs. Physicochemical and structural characterization was carried out using dynamic light scattering (DLS), Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM). Results: The mean particle sizes of Tamoxifen nanoparticles, Gemifloxacin liposomes and LCHNPs were 175.3 ± 1.97 nm, 201.2 ± 2.45 nm and 215.7 ± 2.25 nm, with zeta potentials of +5.5 mV, −12.9 mV and +0.6 mV, respectively. Encapsulation efficiencies reached 96.41 ± 0.66% for nanoparticles and 91.22 ± 1.1% for liposomes. FTIR confirmed successful drug incorporation, while SEM imaging demonstrated smooth particle surfaces. LCHNPs exhibited the lowest IC50 value among the tested formulations (IC₅₀ = 3.83 µM). RT-qPCR (quantitative reverse transcription polymerase chain reaction) analysis demonstrated a significant upregulation of CHEK2 (2.67 ± 1.66-fold) and downregulation of BRCA1 (0.65 ± 0.19-fold) in the LCHNP-treated group compared with the disease control. In-vivo evaluation in a DMBA (dimethylbenz[a]anthracene)-induced mammary tumor model in female Albino Wistar rats (n = 6/group) confirmed the enhanced antitumor efficacy of LCHNPs, as evidenced by reduced tumor incidence and favorable biochemical, hematological and histopathological profiles. Conclusion: Lipid-coated hybrid nanoparticles exhibited enhanced anticancer activity. This study provides a preclinical evaluation of a dual-drug lipid-coated PLGA hybrid nanoparticle co-delivering Tamoxifen and Gemifloxacin, a formulation that has not been previously reported for breast cancer therapy.